Inhibition of mitogen activated protein kinases increases the sensitivity of A549 lung cancer cells to the cytotoxicity induced by a kava chalcone analog

PubMed Central

Warmka, Janel K.; Solberg, Eric L.; Zeliadt, Nicholette A.; Srinivasan, Balasubramanian; Charlson, Aaron T.; Xing, Chengguo; Wattenberg, Elizabeth V.

2012-01-01

We are interested in investigating the biological activity of chalcones, a major class of compounds found in the beverage kava, in order to develop potent and selective chemopreventive candidates. Consumption of kava in the South Pacific Islands is inversely correlated with cancer incidence, even among smokers. Accordingly, chalcones have anti-cancer activities in animal and cell culture models. To investigate signaling pathways that affect chalcone action we studied a potent analog, (E)-3-(3-hydroxy-4-methoxyphenyl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one (chalcone-24). Chalcone-24 was selected from a series of chalcone analogs that were synthesized based on the structures derived from flavokawain compounds found in kava, and screened in A549 lung cancer cells for induction of cytotoxicity and inhibition of NF-κB, a transcription factor associated with cell survival. Incubation of A549 cells with chalcone-24 resulted in a dose-dependent inhibition of cell viability, inhibition of NF-κB, activation of caspases, and activation of extracellular signal regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK); ERK1/2 and JNK are mitogen activated protein kinases that play central roles in regulating cell fate. Pharmacological inhibitors of ERK1/2 or JNK increased the sensitivity of A549 cells to chalcone-24-induced cytotoxicity, without affecting NF-κB or caspase activity. These results will help refine the synthesis of chalcone analogs to maximize the combination of actions required to prevent and treat cancer. PMID:22771807

Functional evaluation of synthetic flavonoids and chalcones for potential antiviral and anticancer properties.

PubMed

Mateeva, Nelly; Eyunni, Suresh V K; Redda, Kinfe K; Ononuju, Ucheze; Hansberry, Tony D; Aikens, Cecilia; Nag, Anita

2017-06-01

Flavonoids, stilbenes, and chalcones are plant secondary metabolites that often possess diverse biological activities including anti-inflammatory, anti-cancer, and anti-viral activities. The wide range of bioactivities poses a challenge to identify their targets. Here, we studied a set of synthetically generated flavonoids and chalcones to evaluate for their biological activity, and compared similarly substituted flavonoids and chalcones. Substituted chalcones, but not flavonoids, showed inhibition of viral translation without significantly affecting viral replication in cells infected with hepatitis C virus (HCV). We suggest that the chalcones used in this study inhibit mammalian target of rapamycin (mTOR) pathway by ablating phosphorylation of ribosomal protein 6 (rps6), and also the kinase necessary for phosphorylating rps6 in Huh7.5 cells (pS6K1). In addition, selected chalcones showed inhibition of growth in Ishikawa, MCF7, and MDA-MB-231 cells resulting an IC 50 of 1-6µg/mL. When similarly substituted flavonoids were used against the same set of cancer cells, we did not observe any inhibitory effect. Together, we report that chalcones show potential for anti-viral and anti-cancer activities compared to similarly substituted flavonoids. Copyright © 2017 Elsevier Ltd. All rights reserved.

Novel 1-(7-ethoxy-1-benzofuran-2-yl) substituted chalcone derivatives: Synthesis, characterization and anticancer activity.

PubMed

Coskun, Demet; Erkisa, Merve; Ulukaya, Engin; Coskun, Mehmet Fatih; Ari, Ferda

2017-08-18

Cancer treatment still requires new compounds to be discovered. Chalcone and its derivatives exhibit anticancer potential in different cancer cells. A new series of benzofuran substituted chalcone derivatives was synthesized by the base-catalyzed Claisen-Schmidt reaction of the 1-(7-ethoxy-1-benzofuran-2-yl) ethanone with different aromatic aldehydes to yield 1-(7-ethoxy-1-benzofuran-2-yl) substituted chalcone derivatives 3a-j. The derivatives were characterized by elemental analysis, FT-IR, 1 H NMR and 13 C NMR spectroscopy techniques. The anti-growth effect of chalcone compounds was tested in breast cancer (MCF-7), non-small cell lung cancer (A549) and prostate cancer (PC-3) cell lines by the SRB and ATP cell viability assays. Apoptosis was detected by mitochondrial membrane potential, Annexin V staining and caspase 3/7 activity. Formation of reactive oxygen species was determined by DCFDA. The results revealed that chalcone derivatives have anticancer activity with especially chalcone derivative 3a showing cytotoxic effects on cancer cells. In addition, chalcone derivative 3a induced apoptosis through caspase dependent pathways in prostate, lung and breast cancer cells. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Green synthesis of chalcones derivatives as intermediate of flavones and their antibacterial activities

NASA Astrophysics Data System (ADS)

VH, Elfi Susanti; Matsjeh, Sabirin; Wahyuningsih, Tutik Dwi; Mustofa, Redjeki, Tri

2016-02-01

Four chalcones derivatives have been synthesized from 3,4-dimethoxybenzaldehyde and acetophenone derivatives (2-hydroxy acetophenone, 2,4-dihydroxy acetophenone, 2,5-dihydroxy acetophenone and 2,6-dihydroxy acetophenone). The synthesis of these chalcones were conducted by Claisen-Schmidt condensation using grinding techniques at room temperature in the absence of solvents. The chalcones were prepared by grinding together equivalent amount of the approriate hydroxyacetophenone and 3,4-dimethoxybenzaldehyde in the presence of solid sodium hydroxide. Grinding techniques for synthesis of the chalcones derivatives is simple, efficient and environmentally benign compared to conventional methods. Then, the four chalcones derivatives undergo cyclization reactions to produce four flavones after reacted with iodine. The synthesized compounds were characterized by spectrometry (IR, 1H-NMR, 13C-NMR and MS).

Second- and third-order nonlinear optical properties of unsubstituted and mono-substituted chalcones

NASA Astrophysics Data System (ADS)

Abegão, Luis M. G.; Fonseca, Ruben D.; Santos, Francisco A.; Souza, Gabriela B.; Barreiros, André Luis B. S.; Barreiros, Marizeth L.; Alencar, M. A. R. C.; Mendonça, Cleber R.; Silva, Daniel L.; De Boni, Leonardo; Rodrigues, J. J.

2016-03-01

This work describes the second and third orders of nonlinear optics properties of unsubstituted chalcone (C15H12O) and mono-substituted chalcone (C16H14O2) in solution, using hyper-Rayleigh scattering and Z-Scan techniques to determine the first molecular hyperpolarizability (β) and the two-photon absorption (2PA) cross section respectively. β Values of 25.4 × 10-30 esu and 31.6 × 10-30 esu, for unsubstituted and mono-substituted chalcone, respectively, dissolved in methanol have been obtained. The highest values of 2PA cross-sections obtained were 9 GM and 14 GM for unsubstituted and mono-substituted chalcone, respectively. The experimental 2PA cross sections obtained for each chalcone are in good agreement with theoretical results.

Chalcone Derivatives: Promising Starting Points for Drug Design.

PubMed

Gomes, Marcelo N; Muratov, Eugene N; Pereira, Maristela; Peixoto, Josana C; Rosseto, Lucimar P; Cravo, Pedro V L; Andrade, Carolina H; Neves, Bruno J

2017-07-25

Medicinal chemists continue to be fascinated by chalcone derivatives because of their simple chemistry, ease of hydrogen atom manipulation, straightforward synthesis, and a variety of promising biological activities. However, chalcones have still not garnered deserved attention, especially considering their high potential as chemical sources for designing and developing new effective drugs. In this review, we summarize current methodological developments towards the design and synthesis of new chalcone derivatives and state-of-the-art medicinal chemistry strategies (bioisosterism, molecular hybridization, and pro-drug design). We also highlight the applicability of computer-assisted drug design approaches to chalcones and address how this may contribute to optimizing research outputs and lead to more successful and cost-effective drug discovery endeavors. Lastly, we present successful examples of the use of chalcones and suggest possible solutions to existing limitations.

Inhibition of mitogen activated protein kinases increases the sensitivity of A549 lung cancer cells to the cytotoxicity induced by a kava chalcone analog.

PubMed

Warmka, Janel K; Solberg, Eric L; Zeliadt, Nicholette A; Srinivasan, Balasubramanian; Charlson, Aaron T; Xing, Chengguo; Wattenberg, Elizabeth V

2012-08-03

We are interested in investigating the biological activity of chalcones, a major class of compounds found in the beverage kava, in order to develop potent and selective chemopreventive candidates. Consumption of kava in the South Pacific Islands is inversely correlated with cancer incidence, even among smokers. Accordingly, chalcones have anti-cancer activities in animal and cell culture models. To investigate signaling pathways that affect chalcone action we studied a potent analog, (E)-3-(3-hydroxy-4-methoxyphenyl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one (chalcone-24). Chalcone-24 was selected from a series of chalcone analogs that were synthesized based on the structures derived from flavokawain compounds found in kava, and screened in A549 lung cancer cells for induction of cytotoxicity and inhibition of NF-κB, a transcription factor associated with cell survival. Incubation of A549 cells with chalcone-24 resulted in a dose-dependent inhibition of cell viability, inhibition of NF-κB, activation of caspases, and activation of extracellular signal regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK); ERK1/2 and JNK are mitogen activated protein kinases that play central roles in regulating cell fate. Pharmacological inhibitors of ERK1/2 or JNK increased the sensitivity of A549 cells to chalcone-24-induced cytotoxicity, without affecting NF-κB or caspase activity. These results will help refine the synthesis of chalcone analogs to maximize the combination of actions required to prevent and treat cancer. Copyright © 2012 Elsevier Inc. All rights reserved.

Green synthesis of chalcones derivatives as intermediate of flavones and their antibacterial activities

DOE Office of Scientific and Technical Information (OSTI.GOV)

VH, Elfi Susanti, E-mail: elsantivh@yahoo.com; Redjeki, Tri, E-mail: tri-redjeki@yahoo.com; Matsjeh, Sabirin, E-mail: sabirin-mara@yahoo.com

Four chalcones derivatives have been synthesized from 3,4-dimethoxybenzaldehyde and acetophenone derivatives (2-hydroxy acetophenone, 2,4-dihydroxy acetophenone, 2,5-dihydroxy acetophenone and 2,6-dihydroxy acetophenone). The synthesis of these chalcones were conducted by Claisen-Schmidt condensation using grinding techniques at room temperature in the absence of solvents. The chalcones were prepared by grinding together equivalent amount of the approriate hydroxyacetophenone and 3,4-dimethoxybenzaldehyde in the presence of solid sodium hydroxide. Grinding techniques for synthesis of the chalcones derivatives is simple, efficient and environmentally benign compared to conventional methods. Then, the four chalcones derivatives undergo cyclization reactions to produce four flavones after reacted with iodine. The synthesized compoundsmore » were characterized by spectrometry (IR, {sup 1}H-NMR, {sup 13}C-NMR and MS)« less

The design and development of imidazothiazole-chalcone derivatives as potential anticancer drugs.

PubMed

Kamal, Ahmed; Kashi Reddy, Methuku; Viswanath, Arutla

2013-03-01

Imidazothiazole derivatives have long been therapeutically used for the treatment of various diseases. In recent years, the imidazothiazole and chalcone moieties have emerged as important pharmacophores in the development of antitumor agents. Imidazothiazole-chalcone conjugates can be accessed by covalently binding these two powerful pharamacophore units. These conjugates are known to exhibit a wide range of biological properties, including anticancer, antimicrobial, anti-inflammatory and immunosuppressive activities. Their promising biological profile and easy synthetic accessibility have triggered investigations directed at the design and development of new imidazothiazole-chalcone conjugate derivatives as potential chemotherapeutics. The present review focuses on recent reports of the syntheses and anticancer properties of various imidazothiazoles, chalcones and imidazothiazole-linked chalcone conjugates. Furthermore, the authors discuss the structure-activity relationships (SAR) of imidazothiazoles and chalcones and their conjugates as new antitumor agents, as well as in vitro and in vivo evaluation, clinical use and their future therapeutic applications. A large number of imidazothiazoles, chalcones and a new series of imidazothiazole-chalcone conjugates possess potent anticancer activity that could be further developed as drug candidates. Imidazothiazole-based conjugates could also display synergistic effect, and still there is a need to use the drug combinations permitting lower dose and development of new generation of drugs. Despite encouraging observed results for their response to tumors in clinical studies, full characterization of their toxicity is further required for their clinical usage as safe drugs for the treatment of cancer.

The role of chalcones in suppression of NF-κB-mediated inflammation and cancer.

PubMed

Yadav, Vivek R; Prasad, Sahdeo; Sung, Bokyung; Aggarwal, Bharat B

2011-03-01

Although consumption of fruits, vegetables, spices, cereals and pulses has been associated with lower incidence of cancer and other chronic diseases, how these dietary agents and their active ingredients minimize these diseases, is not fully understood. Whether it is oranges, kawa, hops, water-lilly, locorice, wax apple or mulberry, they are all connected by a group of aromatic ketones, called chalcones (1,3-diaryl-2-propen-1-ones). Some of the most significant chalcones identified from these plants include flavokawin, butein, xanthoangelol, 4-hydroxyderricin, cardamonin, 2',4'-dihydroxychalcone, isoliquiritigenin, isosalipurposide, and naringenin chalcone. These chalcones have been linked with immunomodulation, antibacterial, antifungal, antiviral, anti-inflammatory, antioxidant, anticancer, and antidiabetic activities. The current review, however, deals with the role of various chalcones in inflammation that controls both the immune system and tumorigenesis. Inflammatory pathways have been shown to mediate the survival, proliferation, invasion, angiogenesis and metastasis of tumors. How these chalcones modulate inflammatory pathways, tumorigenesis and immune system is the focus of this review. Copyright © 2010 Elsevier B.V. All rights reserved.

Apoptotic effect of chalcone derivatives of 2-acetylthiophene in human breast cancer cells.

PubMed

Fogaça, Tatiana B; Martins, Rosiane M; Begnini, Karine R; Carapina, Caroline; Ritter, Marina; de Pereira, Claudio M P; Seixas, Fabiana K; Collares, Tiago

2017-02-01

A variety of chalcones have demonstrated cytotoxic activity toward several cancer cell lines. This study aimed to investigate the cytotoxicity of four chalcones derivatives of 2-acetylthiophene in human breast cancer cell lines. MCF-7 and MDA-MB-231 cells were treated with synthesized chalcones and the cytotoxicity was evaluated by tetrazolium dye (MTT), live/dead, and DAPI assays. Chalcones significantly decreased MCF-7 and MDA-MB-231 cells viability in vitro in a dose dependent manner. After 48h treatment, the IC 50 values ranging from 5.52 to 34.23μM. Chalcone 3c displayed the highest cytotoxic activity from all the tested compounds. Cytotoxic effects of compounds were confirmed in the live/dead assay. In addition, DAPI staining revealed that these compounds induce death by apoptosis. The data speculate that chalcone derivatives of 2-acetylthiophene may represent a source of therapeutic agents for human breast cancer. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Synthesis and biological evaluation of a series of tangeretin-derived chalcones.

PubMed

Quintin, Jérôme; Desrivot, Julie; Thoret, Sylviane; Le Menez, Patrick; Cresteil, Thierry; Lewin, Guy

2009-01-01

A series of chalcones polyoxygenated on the ring A (with pentamethoxy or 2'-hydroxy-3',4',5',6'-tetramethoxy substitution patterns) was synthesized from tangeretin, a natural Citrus flavonoid. These chalcones were evaluated for their antiproliferative, activation of apoptosis, inhibition of tubulin assembly and antileishmanial activities. Comparison with the reference analogous 3',4',5'-trimethoxylated chalcones showed that such peroxygenated substitution patterns on the ring A were less beneficial to these activities.

Preparing Students for Research: Synthesis of Substituted Chalcones as a Comprehensive Guided-Inquiry Experience

NASA Astrophysics Data System (ADS)

Vyvyan, James R.; Pavia, Donald L.; Lampman, Gary M.; Kriz, George S., Jr.

2002-09-01

A guided inquiry experiment involving the synthesis and characterization of substituted benzalacetophenones (chalcones) is described. The chalcones are produced in the aldol condensation of substituted benzaldehydes with substituted acetophenones. Each student is assigned a different target chalcone and conducts online and printed literature searches on the target. After completing the synthesis and purification of their product, the students compare their data with those found in the literature.

Synthesis and evaluation of chalcone analogues based pyrimidines as angiotensin converting enzyme inhibitors.

PubMed

Bukhari, S N A; Butt, A M; Amjad, M W B; Ahmad, W; Shah, V H; Trivedi, A R

2013-11-01

Hypertension is a widespread and frequently progressive ailment that imparts a foremost threat for cardiovascular and renal disorders. Mammoth efforts are needed for the synthesis of innovative antihypertensive agents to combat this lethal disease. Chalcones have shown antihypertensive activity through inhibition of Angiotensin Converting Enzyme (ACE). Hence, a series of chalcone analogues is synthesized and used as precursor for the synthesis of novel series of pyrimidines. Precursor chalcones were prepared by reacting aldehydes and ketones in presence of sodium hydroxide followed by synthesis of corresponding pyrimidines by reaction with urea in presence of potassium hydroxide. Both groups were then evaluated for their effects on ACE. The results depicted that pyrimidines were more active than chalcones with methoxy (C5 and P5) substitution showing best results to inhibit ACE. Given that chalcone analogues and pyrimidines show a potential as the angiotensin converting enzyme inhibitors.

Effective solubilization of chalcones in micellar phase: Conductivity and voltammetric study

NASA Astrophysics Data System (ADS)

Ahmed, Safeer; Khan, Gul Tiaz; Shah, Syed Sakhawat

2013-12-01

The solubilization of four chalcones, between aqueous and micellar phases of ionic surfactants (SDS and CTAB), was investigated by conductivity and cyclic voltammetry (CV) techniques. From conductivity data, a decrease in the critical micellar concentration (CMC) of the surfactants, in presence of the chalcones was ascribed to the decreased charge density over the surfactants. The results were seconded by thermodynamic parameters including degree of ionization (α), counter ion binding (β), and standard Gibbs free energy of micellization (Δ G {m/○}). The added surfactant decreased the peak current of the oxidized chalcone and shifted the peak potential either positively (in presence of SDS) or negatively (in presence of CTAB). The effect is rationalized as chalcone-surfactant interaction and quantitated as binding constant ( K b) assorting values from 8.78 to 552.97 M-1. The preferred solubilization of the chalcones in the micellar phase has been inferred.

Cytotoxicity of trans-chalcone and licochalcone A against breast cancer cells is due to apoptosis induction and cell cycle arrest.

PubMed

Bortolotto, Luis Felipe Buso; Barbosa, Flávia Regina; Silva, Gabriel; Bitencourt, Tamires Aparecida; Beleboni, Rene Oliveira; Baek, Seung Joon; Marins, Mozart; Fachin, Ana Lúcia

2017-01-01

Chalcones are precursors of flavonoids that exhibit structural heterogeneity and potential antitumor activity. The objective of this study was to characterize the cytotoxicity of trans-chalcone and licochalcone A (LicoA 1 ) against a breast cancer cell line (MCF-7) and normal murine fibroblasts (3T3). Also the mechanisms of the anti-cancer activity of these two compounds were studied. The alkaline comet assay revealed dose-dependent genotoxicity, which was more responsive against the tumor cell line, compared to the 3T3 mouse fibroblast cell line. Flow cytometry showed that the two chalcones caused the cell cycle arrest in the G1 phase and induced apoptosis in MCF-7 cells. Using PCR Array, we found that trans-chalcone and LicoA trigger apoptosis mediated by the intrinsic pathway as demonstrated by the inhibition of Bcl-2 and induction of Bax. In western blot assay, the two chalcones reduced the expression of cell death-related proteins such as Bcl-2 and cyclin D1 and promoted the cleavage of PARP. However, only trans-chalcone induced the expression of the CIDEA gene and protein in these two experiments. Furthermore, transient transfections of MCF-7 using a construction of a promoter-luciferase vector showed that trans-chalcone induced the expression of the CIDEA promoter activity in 24 and 48h. In conclusion, the results showed that trans-chalcone promoted high induction of the CIDEA promoter gene and protein, which is related to DNA fragmentation during apoptosis. Copyright © 2016. Published by Elsevier Masson SAS.

In vitro and in vivo Effects of Free and Chalcones-Loaded Nanoemulsions: Insights and Challenges in Targeted Cancer Chemotherapies

PubMed Central

Winter, Evelyn; Dal Pizzol, Carine; Locatelli, Claudriana; Silva, Adny H.; Conte, Aline; Chiaradia-Delatorre, Louise D.; Nunes, Ricardo J.; Yunes, Rosendo A.; Creckzynski-Pasa, Tânia B.

2014-01-01

Several obstacles are encountered in conventional chemotherapy, such as drug toxicity and poor stability. Nanotechnology is envisioned as a strategy to overcome these effects and to improve anticancer therapy. Nanoemulsions comprise submicron emulsions composed of biocompatible lipids, and present a large surface area revealing interesting physical properties. Chalcones are flavonoid precursors, and have been studied as cytotoxic drugs for leukemia cells that induce cell death by different apoptosis pathways. In this study, we encapsulated chalcones in a nanoemulsion and compared their effect with the respective free compounds in leukemia and in non-tumoral cell lines, as well as in an in vivo model. Free and loaded-nanoemulsion chalcones induced a similar anti-leukemic effect. Free chalcones induced higher toxicity in VERO cells than chalcones-loaded nanoemulsions. Similar results were observed in vivo. Free chalcones induced a reduction in weight gain and liver injuries, evidenced by oxidative stress, as well as an inflammatory response. Considering the high toxicity and the side effects induced generally by all cancer chemotherapies, nanotechnology provides some options for improving patients’ life quality and/or increasing survival rates. PMID:25264679

Differential Effects of Structural Modifications on the Competition of Chalcones for the PIB Amyloid Imaging Ligand-Binding Site in Alzheimer's Disease Brain and Synthetic Aβ Fibrils.

PubMed

Fosso, Marina Y; McCarty, Katie; Head, Elizabeth; Garneau-Tsodikova, Sylvie; LeVine, Harry

2016-02-17

Alzheimer's disease (AD) is a complex brain disorder that still remains ill defined. In order to understand the significance of binding of different clinical in vivo imaging ligands to the polymorphic pathological features of AD brain, the molecular characteristics of the ligand interacting with its specific binding site need to be defined. Herein, we observed that tritiated Pittsburgh Compound B ((3)H-PIB) can be displaced from synthetic Aβ(1-40) and Aβ(1-42) fibrils and from the PIB binding complex purified from human AD brain (ADPBC) by molecules containing a chalcone structural scaffold. We evaluated how substitution on the chalcone scaffold alters its ability to displace (3)H-PIB from the synthetic fibrils and ADPBC. By comparing unsubstituted core chalcone scaffolds along with the effects of bromine and methyl substitution at various positions, we found that attaching a hydroxyl group on the ring adjacent to the carbonyl group (ring I) of the parent member of the chalcone family generally improved the binding affinity of chalcones toward ADPBC and synthetic fibrils F40 and F42. Furthermore, any substitution on ring I at the ortho-position of the carbonyl group greatly decreases the binding affinity of the chalcones, potentially as a result of steric hindrance. Together with the finding that neither our chalcones nor PIB interact with the Congo Red/X-34 binding site, these molecules provide new tools to selectively probe the PIB binding site that is found in human AD brain, but not in brains of AD pathology animal models. Our chalcone derivatives also provide important information on the effects of fibril polymorphism on ligand binding.

Different effects of two cyclic chalcone analogues on redox status of Jurkat T cells.

PubMed

Rozmer, Zsuzsanna; Berki, Tímea; Maász, Gábor; Perjési, Pál

2014-12-01

Chalcones are intermediary compounds of the biosynthetic pathway of the naturally flavonoids. Previous studies have demonstrated that chalcones and their conformationally rigid cyclic analogues have tumour cell cytotoxic and chemopreventive effects. It has been shown that equitoxic doses of the two cyclic chalcone analogues (E)-2-(4'-methoxybenzylidene)-(2) and (E)-2-(4'-methylbenzylidene)-1-benzosuberone (3) have different effect on cell cycle progress of the investigated Jurkat cells. It was also found that the compounds affect the cellular thiol status of the treated cells and show intrinsic (non-enzyme-catalyzed) reactivity towards GSH under cell-free conditions. In order to gain new insights into the cytotoxic mechanism of the compounds, effects on the redox status and glutathione level of Jurkat cells were investigated. Detection of intracellular ROS level in Jurkat cells exposed to 2 and 3 was performed using the dichlorofluorescein-assay. Compound 2 did not influence ROS activity either on 1 or 4h exposure; in contrast, chalcone 3 showed to reduce ROS level at both timepoints. The two compounds had different effects on cellular glutathione status as well. Compound 2 significantly increased the oxidized glutathione (GSSG) level showing an interference with the cellular antioxidant defence. On the contrary, chalcone 3 enhanced the reduced glutathione level, indicating enhanced cellular antioxidant activity. To investigate the chalcone-GSH conjugation reactions under cellular conditions, a combination of a RP-HPLC method with electrospray ionization mass spectrometry (ESI-MS) was performed. Chalcone-GSH adducts could not be observed either in the cell supernatant or the cell sediment after deproteinization. The investigations provide further details of dual - cytotoxic and chemopreventive - effects of the cyclic chalcone analogues. Copyright © 2014 Elsevier Ltd. All rights reserved.

Hydroxyapatite catalyzed aldol condensation: Synthesis, spectral linearity, antimicrobial and insect antifeedant activities of some 2,5-dimethyl-3-furyl chalcones

NASA Astrophysics Data System (ADS)

Subramanian, M.; Vanangamudi, G.; Thirunarayanan, G.

2013-06-01

A series of 2,5-dimethyl-3-furyl chalcones [2E-1-(2,5-dimethyl-3-furyl)-3-(substituted phenyl)-2-propen-1-ones] have been synthesized by Hydrotalcite catalyzed aldol condensation between 3-acetyl-2,5-dimethylfuron and substituted benzaldehydes. Yields of chalcones are more than 80%. These chalcones were characterized by their physical constants and spectral data. The group frequencies of infrared ν(cm-1) of CO s-cis and s-trans, CH in-plane and out of plane, CHdbnd CH out of plane, lbond2 Cdbnd Crbond2 out of plane modes, NMR chemical shifts δ(ppm) of Hα, Hβ, CO, Cα and Cβ of these chalcones were correlated with Hammett substituent constants, F and R parameters using single and multi-regression analyses. From the results of statistical analyses, the effects of substituents on the group frequencies are explained. Antibacterial, antifungal and insect antifeedant activities of these chalcones have been studied.

Apoptosis-inducing effects and growth inhibitory of a novel chalcone, in human hepatic cancer cells and lung cancer cells.

PubMed

Dong, Naiwei; Liu, Xin; Zhao, Tong; Wang, Lei; Li, Huimin; Zhang, Shuqian; Li, Xia; Bai, Xue; Zhang, Yong; Yang, Baofeng

2018-05-29

Apoptosis is an important biological phenomenon, which affects many diseases, such as cancer and Alzheimer's disease. In the present study, we observed that chalcone 9X, an aromatic ketone, induced apoptosis of human hepatic and lung cancer cells and inhibited cancer cell migration and invasion. This compound strongly suppressed the growth of tumor in a mouse model of xenograft tumors. The anticancer activity of chalcone 9X was equivalent to 5-fluorouracil (5-FU) as a positive control agent, whereas the toxic effect of chalcone 9X in non-cancer cells was weaker than 5-FU. Molecular docking results showed that chalcone 9X could act on the active sites of pro-apoptotic proteins capspases-3 and -8 to induce apoptotic death of cancer cells. Our findings suggest that chalcone 9X might be considered a candidate compound of novel anticancer drug in the future. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

The Role of Chalcones in Suppression of NF-κB-Mediated Inflammation and Cancer

PubMed Central

Yadav, Vivek R.; Prasad, Sahdeo; Sung, Bokyung; Aggarwal, Bharat B.

2010-01-01

Although consumption of fruits, vegetables, spices, cereals and pulses has been associated with lower incidence of cancer and other chronic diseases, how these dietary agents and their active ingredients minimize these diseases, is not fully understood. Whether it is oranges, kawa, hops, water-lilly, locorice, wax apple or mulberry, they are all connected by a group of aromatic ketones, called chalcones (1,3-diaryl-2-propen-1-ones). Some of the most significant chalcones identified from these plants include flavokawin, butein, xanthoangelol, 4-hydroxyderricin, cardamonin, 2′,4′-dihydroxychalcone, isoliquiritigenin, isosalipurposide, and naringenin. These chalcones have been linked with immunomodulation, antibacterial, antifungal, antiviral, anti-inflammatory, antioxidant, anticancer, and antidiabetic activities. The current review, however, deals with the role of various chalcones in inflammation that controls both the immune system and tumorigenesis. Inflammatory pathways have been shown to mediate the survival, proliferation, invasion, angiogenesis and metastasis of tumors. How these chalcones modulate inflammatory pathways, tumorigenesis and immune system is the focus of this review. PMID:21184860

Chalcones: structural requirements for antioxidant, estrogenic and antiproliferative activities.

PubMed

Calliste, C A; Le Bail, J C; Trouillas, P; Pouget, C; Habrioux, G; Chulia, A J; Duroux, J L

2001-01-01

Flavonoids are largely studied for their biological properties and particularly for their scavenging and antioxidant activities. In the present study, we first evaluated the antioxidant and the estrogenic actions of chalcones, then we tested their effects on MCF-7 cell proliferation. Chalcones are unique in the flavonoids family in lacking a heterocyclic C ring. We tested substituted chalcones with different numbers and different positions of the hydroxy groups: 2'-hydroxychalcone, 4'-hydroxychalcone, 4-hydroxychalcone, 2',4-dihydroxychalcone, isoliquiritigenin, 2',4'-dihydroxychalcone, phloretin and naringenin chalcone. For the antioxidant tests we established the importance of the alpha-beta double bond and the 6'-hydroxy group. The establishment of the structure-activity relationship for the estrogenic properties showed a correlation between the antioxidant and the estrogenic properties. The importance of conformation and hydroxy group positions observed for chalcones, having antioxidant and estrogenic properties, was also observed on MCF-7 cell growth with the same structure-activity relationship. The role of electron and hydrogen transfer in the correlation between these three biological activities was discussed.

Cytotoxic and apoptotic effects of chalcone derivatives of 2-acetyl thiophene on human colon adenocarcinoma cells.

PubMed

de Vasconcelos, Alana; Campos, Vinicius Farias; Nedel, Fernanda; Seixas, Fabiana Kömmling; Dellagostin, Odir A; Smith, Kevin R; de Pereira, Cláudio Martin Pereira; Stefanello, Francieli Moro; Collares, Tiago; Barschak, Alethéa Gatto

2013-06-01

Recent studies report that chalcones exhibit cytotoxicity to human cancer cell lines. Typically, the form of cell death induced by these compounds is apoptosis. In the context of the discovery of new anticancer agents and in light of the antitumour potential of several chalcone derivatives, in the present study, we synthesized and tested the cytotoxicity of six chalcone derivatives on human colon adenocarcinoma cells. Six derivatives of 3-phenyl-1-(thiophen-2-yl) prop-2-en-1-one were prepared and characterized on the basis of their (1) H and (13) C NMR spectra. HT-29 cells were treated with synthesized chalcones on two concentrations by three different incubation times. Cells were evaluated by cell morphology, Tetrazolium dye (MTT) colorimetric assay, live/dead, flow cytometry (annexin V) and gene expression analyses to determine the cytotoxic way. Chalcones 3-(4-bromophenyl)-1-(thiophen-2-yl)prop-2-en-1-one (C06) and 3-(2-nitrophenyl)-1-(thiophen-2-yl)prop-2-en-1-one (C09) demonstrated higher cytotoxicity than other chalcones as shown by cell morphology, live/dead and MTT assays. In addition, C06 induced apoptosis on flow cytometry annexin V assay. These data were confirmed by a decreased expression of anti-apoptotic genes and increased pro-apoptotic genes. Our findings indicate in summary that the cytotoxic activity of chalcone C06 on colorectal carcinoma cells occurs by apoptosis. Copyright © 2012 John Wiley & Sons, Ltd.

Natural chalcones as dual inhibitors of HDACs and NF-κB

PubMed Central

ORLIKOVA, B.; SCHNEKENBURGER, M.; ZLOH, M.; GOLAIS, F.; DIEDERICH, M.; TASDEMIR, D.

2012-01-01

Histone deacetylase enzymes (HDACs) are emerging as a promising biological target for cancer and inflammation. Using a fluorescence assay, we tested the in vitro HDAC inhibitory activity of twenty-one natural chalcones, a widespread group of natural products with well-known anti-inflammatory and antitumor effects. Since HDACs regulate the expression of the transcription factor NF-κB, we also evaluated the inhibitory potential of the compounds on NF-κB activation. Only four chalcones, isoliquiritigenin (no. 10), butein (no. 12), homobutein (no. 15) and the glycoside marein (no. 21) showed HDAC inhibitory activity with IC50 values of 60–190 μM, whereas a number of compounds inhibited TNFα-induced NF-κB activation with IC50 values in the range of 8–41 μM. Interestingly, three chalcones (nos. 10, 12 and 15) inhibited both TNFα-induced NF-κB activity and total HDAC activity of classes I, II and IV. Molecular modeling and docking studies were performed to shed light into dual activity and to draw structure-activity relationships among chalcones (nos. 1–21). To the best of our knowledge this is the first study that provides evidence for HDACs as potential drug targets for natural chalcones. The dual inhibitory potential of the selected chalcones on NF-κB and HDACs was investigated for the first time. This study demonstrates that chalcones can serve as lead compounds in the development of dual inhibitors against both targets in the treatment of inflammation and cancer. PMID:22710558

Solvent-Free Synthesis of Chalcones

ERIC Educational Resources Information Center

Palleros, Daniel R.

2004-01-01

The synthesis of twenty different chalcones in the absence of solvent is presented. The results indicated that out of the twenty different chalcones investigated seventeen can be obtained in a matter of minutes by mixing the corresponding benzaldehyde and acetophenone in the presence of solid NaOH in a mortar with pestle.

Molecular Targeted Approaches to Cancer Therapy and Prevention Using Chalcones

PubMed Central

Jandial, Danielle D.; Blair, Christopher A.; Zhang, Saiyang; Krill, Lauren S.; Zhang, Yan-Bing; Zi, Xiaolin

2014-01-01

There is an emerging paradigm shift in oncology that seeks to emphasize molecularly targeted approaches for cancer prevention and therapy. Chalcones (1,3-diphenyl-2-propen-1-ones), naturally-occurring compounds with widespread distribution in spices, tea, beer, fruits and vegetables, consist of open-chain flavonoids in which the two aromatic rings are joined by a three-carbon α, β-unsaturated carbonyl system. Due to their structural diversity, relative ease of chemical manipulation and reaction of α, β-unsaturated carbonyl moiety with cysteine residues in proteins, some lead chalcones from both natural products and synthesis have been identified in a variety of screening assays for modulating important pathways or molecular targets in cancers. These pathways and targets that are affected by chalcones include MDM2/p53, tubulin, proteasome, NF-kappa B, TRIAL/death receptors and mitochondria mediated apoptotic pathways, cell cycle, STAT3, AP-1, NRF2, AR, ER, PPAR-γ and β-catenin/Wnt. Compared to current cancer targeted therapeutic drugs, chalcones have the advantages of being inexpensive, easily available and less toxic; the ease of synthesis of chalcones from substituted benzaldehydes and acetophenones also makes them an attractive drug scaffold. Therefore, this review is focused on molecular targets of chalcones and their potential implications in cancer prevention and therapy. PMID:24467530

Unambiguous Identification of β-Tubulin as the Direct Cellular Target Responsible for the Cytotoxicity of Chalcone by Photoaffinity Labeling.

PubMed

Zhou, Bo; Yu, Xingxin; Zhuang, Chunlin; Villalta, Peter; Lin, Yong; Lu, Junxuan; Xing, Chengguo

2016-07-05

Chalcone is a simple and potentially privileged structure in medicinal chemistry with a diverse repertoire of biological activities, among which cytotoxicity is of particular interest. The sharp structure-activity relationship (SAR) for chalcone's cytotoxicity suggests structure-specific target interactions. Despite the numerous putative targets proposed, evidence for direct target interactions in cells is unavailable. In this study, guided by the sharp cytotoxic SAR, we developed a cytotoxic chalcone-based photoaffinity labeling (PAL) probe, (E)-3-(3-azidophenyl)-1-[3,5-dimethoxy-4-(prop-2-yn-1-yloxy)phenyl]-2-methylprop-2-en-1-one (C95; IC50 : 0.38±0.01 μm), along with two structurally similar non-cytotoxic probes. These probes were used to search for the direct cellular target responsible for chalcone's cytotoxicity through intact cell-based PAL experiments, in which β-tubulin was identified to specifically interact with the cytotoxic probe (i.e., C95) but not the non-cytotoxic probes. A set of phenotypical and biochemical assays further reinforced β-tubulin as the cytotoxic target of chalcones. Peptide mass quantitation by mass spectrometric analysis revealed one peptide potentially labeled by C95, providing information on chalcone's binding site on β-tubulin. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Highly effective, regiospecific reduction of chalcone by cyanobacteria leads to the formation of dihydrochalcone: two steps towards natural sweetness.

PubMed

Żyszka, Beata; Anioł, Mirosław; Lipok, Jacek

2017-08-04

Chalcones are the biogenetic precursors of all known flavonoids, which play an essential role in various metabolic processes in photosynthesizing organisms. The use of whole cyanobacteria cells in a two-step, light-catalysed regioselective bio-reduction of chalcone, leading to the formation of the corresponding dihydrochalcone, is reported. The prokaryotic microalgae cyanobacteria are known to produce phenolic compounds, including flavonoids, as natural components of cells. It seems logical that organisms producing such compounds possess a suitable "enzymatic apparatus" to carry out their biotransformation. Therefore, determination of the ability of whole cells of selected cyanobacteria to carry out biocatalytic transformations of chalcone, the biogenetic precursor of all known flavonoids, was the aim of our study. Chalcone was found to be converted to dihydrochalcone by all examined cyanobacterial strains; however, the effectiveness of this process depends on the strain with biotransformation yields ranging from 3% to >99%. The most effective biocatalysts are Anabaena laxa, Aphanizomenon klebahnii, Nodularia moravica, Synechocystis aquatilis (>99% yield) and Merismopedia glauca (92% yield). The strains Anabaena sp. and Chroococcus minutus transformed chalcone in more than one way, forming a few products; however, dihydrochalcone was the dominant product. The course of biotransformation shed light on the pathway of chalcone conversion, indicating that the process proceeds through the intermediate cis-chalcone. The scaled-up process, conducted on a preparative scale and by using a mini-pilot photobioreactor, fully confirmed the high effectiveness of this bioconversion. Moreover, in the case of the mini-pilot photobioreactor batch cultures, the optimization of culturing conditions allowed the shortening of the process conducted by A. klebahnii by 50% (from 8 to 4 days), maintaining its >99% yield. This is the first report related to the use of whole cells of halophilic and freshwater cyanobacteria strains in a two-step, light-catalysed regioselective bio-reduction of chalcone, leading to the formation of the corresponding dihydrochalcone. The total bioconversion of chalcone in analytical, preparative, and mini-pilot scales of this process creates the possibility of its use in the food industry for the production of natural sweeteners.

Chalcones suppress fatty acid-induced lipid accumulation through a LKB1/AMPK signaling pathway in HepG2 cells.

PubMed

Zhang, Tianshun; Yamamoto, Norio; Ashida, Hitoshi

2014-06-01

Excessive lipid accumulation in the liver has been proposed to cause hyperlipidemia, diabetes and fatty liver disease. 4-Hydroxyderricin (4HD), xanthoangelol (XAG), cardamonin (CAR) and flavokawain B (FKB) are chalcones that have exhibited various biological effects against obesity, inflammation, and diabetes; however, little is known about the inhibitory effects of these chalcones on fatty liver disease. In the present study, we investigated the ability of 4HD, XAG, CAR, and FKB to reduce lipid accumulation in hepatocytes. When HepG2 cells were treated with a mixture of fatty acids (FAs; palmitic acid : oleic acid = 1 : 2 ratio), significant lipid accumulation was observed. Under the same experimental conditions, addition of chalcones at 5 μM significantly suppressed the FA-induced lipid accumulation. We found that the expression of sterol regulatory element-binding protein-1 (SREBP-1), a key molecule involved in lipogenesis, was decreased in these chalcone-treated cells. We also found that these chalcones increased the expression of peroxisome proliferator-activated receptor α (PPARα), which is involved in FA oxidation. Moreover, these chalcones increased phosphorylation of AMP-activated protein kinase (AMPK) and liver kinase B1 (LKB1), upstream regulators of SREBP-1 and PPARα. We confirmed that an AMPK inhibitor, compound C, reversed chalcone-induced changes in SREBP-1 and PPARα expression in the HepG2 cells. Collectively, we found that 4HD, XAG, CAR, and XAG attenuated lipid accumulation through activation of the LKB1/AMPK signaling pathway in HepG2 cells.

Antitumor effects of the flavone chalcone: inhibition of invasion and migration through the FAK/JNK signaling pathway in human gastric adenocarcinoma AGS cells.

PubMed

Lin, Su-Hsuan; Shih, Yuan-Wei

2014-06-01

Chalcones (benzylideneacetophenone) are cancer-preventive food components found in a human diet rich in fruits and vegetables. In this study, we first report the chemopreventive effect of chalcone in human gastric adenocarcinoma cell lines: AGS. The results showed that chalcone could inhibit the abilities of the adhesion, invasion, and migration by cell-matrix adhesion assay, Boyden chamber invasion/migration assay, and wound-healing assay. Molecular data showed that the effect of chalcone in AGS cells might be mediated via sustained inactivation of the phosphorylation of focal adhesion kinase (FAK) and c-Jun N-terminal kinase 1 and 2 (JNK1/2) signal involved in the downregulation of the expressions of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9). Next, chalcone-treated AGS cells showed tremendous decrease in the phosphorylation and degradation of inhibitor of kappaBα (IκBα), the nuclear level of NF-κB, and the binding ability of NF-κB to NF-κB response element. Furthermore, treating FAK small interfering RNA (FAK siRNA) and specific inhibitor for JNK (SP600125) to AGS cells could reduce the phosphorylation of JNK1/2 and the activity of MMP-2 and MMP-9. Our results revealed that chalcone significantly inhibited the metastatic ability of AGS cells by reducing MMP-2 and MMP-9 expressions concomitantly with a marked reduction on cell invasion and migration through suppressing and JNK signaling pathways. We suggest that chalcone may offer the application in clinical medicine.

Chalcones from Angelica keiskei: Evaluation of Their Heat Shock Protein Inducing Activities.

PubMed

Kil, Yun-Seo; Choi, Seul-Ki; Lee, Yun-Sil; Jafari, Mahtab; Seo, Eun-Kyoung

2015-10-23

Five new chalcones, 4,2',4'-trihydroxy-3'-[(2E,5E)-7-methoxy-3,7-dimethyl-2,5-octadienyl]chalcone (1), (±)-4,2',4'-trihydroxy-3'-[(2E)-6-hydroxy-7-methoxy-3,7-dimethyl-2-octenyl]chalcone (2), 4,2',4'-trihydroxy-3'-[(2E)-3-methyl-5-(1,3-dioxolan-2-yl)-2-pentenyl]chalcone (3), 2',3'-furano-4-hydroxy-4'-methoxychalcone (4), and (±)-4-hydroxy-2',3'-(2,3-dihydro-2-methoxyfurano)-4'-methoxychalcone (5), were isolated from the aerial parts of Angelica keiskei Koidzumi together with eight known chalcones, 6-13, which were identified as (±)-4,2',4'-trihydroxy-3'-[(6E)-2-hydroxy-7-methyl-3-methylene-6-octenyl]chalcone (6), xanthoangelol (7), xanthoangelol F (8), xanthoangelol G (9), 4-hydroxyderricin (10), xanthoangelol D (11), xanthoangelol E (12), and xanthoangelol H (13), respectively. Chalcones 1-13 were evaluated for their promoter activity on heat shock protein 25 (hsp25, murine form of human hsp27). Compounds 1 and 6 activated the hsp25 promoter by 21.9- and 29.2-fold of untreated control at 10 μM, respectively. Further protein expression patterns of heat shock factor 1 (HSF1), HSP70, and HSP27 by 1 and 6 were examined. Compound 6 increased the expression of HSF1, HSP70, and HSP27 by 4.3-, 1.5-, and 4.6-fold of untreated control, respectively, without any significant cellular cytotoxicities, whereas 1 did not induce any expression of these proteins. As a result, 6 seems to be a prospective HSP inducer.

New chalcones bearing a long-chain alkylphenol from the rhizomes of Alpinia galanga.

PubMed

Yang, Wan-Qiu; Gao, Yuan; Li, Ming; Miao, De-Ren; Wang, Fei

2015-01-01

Three novel chalcones bearing a long-chain alkylphenol, galanganones A-C (1-3), were isolated from the rhizomes of Alpinia galanga. Their structures were elucidated by extensive spectroscopic analysis including 2D NMR experiments. Compounds 1-3 represent the first examples of long-chain alkylphenol-coupled chalcone.

[Studies on flavonoids of Oxytropis falcata].

PubMed

Lu, Fang; Xu, Xiao-Jie

2007-02-01

To investigate the flavonoids of Oxytropisfalcata. Compounds were isolated by column chromatography using silica gel, Sephadex LH -20 and ODS as the adsorbents. Their structures were elucidated by NMR and MS spectroscopic data. Eight compounds were isolated and elucidated as 2', 4'-dihydroxy-4-methoxy chalcone (1), 2', 4'-dihydroxy chalcone (2), 5,7-dihydroxy-4'-methoxy flavonol (3), 7-hydroxy-4'-methoxy flavanones (4), 3', 7-dihydroxy-2',4'-dimethoxy isoflavan (5), 2'-hydroxy-4'-methoxy chalcone (6), 2'-methoxy-4'-hydroxy chalcone (7), 2',4'-dihydroxy dihydrochalcone (8). All compounds were obtained from O. falcata for the first time.

trans-Chalcone, a flavonoid precursor, inhibits UV-induced skin inflammation and oxidative stress in mice by targeting NADPH oxidase and cytokine production.

PubMed

Martinez, Renata M; Pinho-Ribeiro, Felipe A; Steffen, Vinicius S; Caviglione, Carla V; Fattori, Victor; Bussmann, Allan J C; Bottura, Carolina; Fonseca, Maria J V; Vignoli, Josiane A; Baracat, Marcela M; Georgetti, Sandra R; Verri, Waldiceu A; Casagrande, Rubia

2017-07-01

trans-Chalcone is a plant flavonoid precursor, which lacks broad investigation on its biological activity in inflammatory processes. In the present study, anti-inflammatory and antioxidant mechanisms of systemic administration with trans-chalcone, a flavonoid precursor, on ultraviolet (UV) irradiation-induced skin inflammation and oxidative stress in hairless mice were investigated by the following parameters: skin edema, myeloperoxidase activity (neutrophil marker), matrix metalloproteinase-9 activity, reduced glutathione levels, catalase activity, lipid peroxidation products, superoxide anion production, gp 91phox (NADPH oxidase subunit) mRNA expression by quantitative PCR and cytokine production by ELISA. Systemic treatment with trans-chalcone inhibited skin inflammation by reducing skin edema and neutrophil recruitment, and also inhibited matrix metalloproteinase-9 activity. trans-Chalcone also inhibited oxidative stress, gp 91phox mRNA expression, and the production of a wide range of pro-inflammatory cytokines, while it did not affect anti-inflammatory cytokines induced by UV irradiation. However, trans-chalcone did not prevent oxidative stress in vitro, suggesting that its in vivo effect is more related to anti-inflammatory properties rather than a direct antioxidant effect. In conclusion, treatment with trans-chalcone inhibited UV-induced skin inflammation resulting in oxidative stress inhibition in vivo. Therefore, systemic supplementation with this compound may represent an important therapeutic approach in inflammatory skin diseases induced by UV irradiation.

Chalcone-Induced Apoptosis through Caspase-Dependent Intrinsic Pathways in Human Hepatocellular Carcinoma Cells.

PubMed

Ramirez-Tagle, Rodrigo; Escobar, Carlos A; Romero, Valentina; Montorfano, Ignacio; Armisén, Ricardo; Borgna, Vincenzo; Jeldes, Emanuel; Pizarro, Luis; Simon, Felipe; Echeverria, Cesar

2016-02-22

Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed cancers worldwide. Chemoprevention of HCC can be achieved through the use of natural or synthetic compounds that reverse, suppress or prevent the development of cancer progression. In this study, we investigated the antiproliferative effects and the mechanism of action of two compounds, 2,3,4'-trimethoxy-2'-hydroxy-chalcone (CH1) and 3'-bromo-3,4-dimethoxy-chalcone (CH2), over human hepatoma cells (HepG2 and Huh-7) and cultured mouse hepatocytes (HepM). Cytotoxic effects were observed over the HepG2 and Huh-7, and no effects were observed over the HepM. For HepG2 cells, treated separately with each chalcone, typical apoptotic laddering and nuclear condensation were observed. Additionally, the caspases and Bcl-2 family proteins activation by using Western blotting and immunocytochemistry were studied. Caspase-8 was not activated, but caspase-3 and -9 were both activated by chalcones in HepG2 cells. Chalcones also induced reactive oxygen species (ROS) accumulation after 4, 8 and 24 h of treatment in HepG2 cells. These results suggest that apoptosis in HepG2 was induced through: (i) a caspase-dependent intrinsic pathway; and (ii) by alterations in the cellular levels of Bcl-2 family proteins, and also, that the chalcone moiety could be a potent candidate as novel anticancer agents acting on human hepatomas.

Anti-cancer activity of trans-chalcone in osteosarcoma: Involvement of Sp1 and p53.

PubMed

Silva, Gabriel; Marins, Mozart; Fachin, Ana Lúcia; Lee, Seong-Ho; Baek, Seung Joon

2016-10-01

Osteosarcoma is the most common bone cancer. Although the emergence of multidrug therapies has improved available treatments for osteosarcoma, approximately 30% of patients will still develop metastasis. Currently, much anticancer therapy uses drugs that affect oncogenes/tumor suppressor genes, such as p53 (up-regulation) and Sp1 (down-regulation). Chalcones are secondary metabolites of plants and have been demonstrated to induce apoptosis in human cancer cells. Building on this knowledge, we evaluated the ability of trans-chalcone to reduce viability, to induce apoptosis, and to alter gene expression of p53 and Sp1 in human osteosarcoma cell lines. We found that treatment of trans-chalcone inhibited growth of osteosarcoma cells in a dose- and time-dependent manner, with significant inhibition at 10 μM after 48 h; apoptosis was also induced in a dose-dependent manner, with 1.9- and 3.6-fold induction at 10 μM and 50 μM, respectively, compared to non-treated cells. Further experiments suggest that trans-chalcone affected Sp1 down-regulation at the transcriptional level, whereas trans-chalcone up-regulated p53 expression at the post-translational level. trans-chalcone and its derivatives could be important in the development of future clinical trials in osteosarcoma. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Antibacterial activity of three newly-synthesized chalcones & synergism with antibiotics against clinical isolates of methicillin-resistant Staphylococcus aureus

PubMed Central

Božić, Dragana D.; Milenković, Marina; Ivković, Branka; Cirković, Ivana

2014-01-01

Background & objectives: Multidrug-resistance of methicillin-resistant Staphylococcus aureus (MRSA) is a serious therapeutical problem. Chalcones belong to a group of naturally occurring flavonoids, usually found in various plant species, and have potent antibacterial, antiviral and antifungal activities. The goal of this study was to evaluate the antibacterial effect of three newly-synthesized chalcones against clinical isolates of MRSA, and their synergism with β-lactam and non- β-lactam antibiotics. Methods: Antimicrobial activity of the three newly-synthesized chalcones was tested against 19 clinical isolates of MRSA and a laboratory control strain of MRSA (ATCC 43300). The synergism with β-lactams: cefotaxime (CFX), ceftriaxone (CTX), and non-β-lactam antibiotics: ciprofloxacin (CIP), gentamicin (GEN) and trimethoprim/sulphamethoxazole (TMP-SMX) was investigated by checkerboard method. Results: All evaluated compounds showed significant anti-MRSA activity with MIC values from 25-200 μg/ml. Observed synergism with antibiotics demonstrated that chalcones significantly enhanced the efficacy of CIP, GEN and TMP-SMX. Interpretation & conclusions: Our study demonstrated that three newly-synthesized chalcones exhibited significant anti-MRSA effect and synergism with non-β-lactam antibiotics. The most effective compound was 1,3-Bis-(2-hydroxy-phenyl)-propenone. Our results provide useful information for future research of possible application of chalcones in combination with conventional anti-MRSA therapy as promising new antimicrobial agents. PMID:25222788

Discovery and structure activity relationships of 2-pyrazolines derived from chalcones from a pest management perspective

USDA-ARS?s Scientific Manuscript database

Synthesis of chalcones and 2-pyrazoline derivatives has been an active field of research due to the established pharmacological effects of these compounds. In this study, a series of chalcone (1a-i), 2-pyrazoline-1-carbothioamides (2a-i) and 2-pyrazoline-1-carboxamide derivatives (3a-g) were synthes...

Radiation and quantum chemical studies of chalcone derivatives.

PubMed

Gaikwad, P; Priyadarsini, K I; Naumov, S; Rao, B S M

2010-08-05

The reactions of oxidizing radicals ((*)OH, Br(2)(*-), and SO(4)(*-)) with -OH-, -CH(3)-, or -NH(2)-substituted indole chalcones and hydroxy benzenoid chalcones were studied by radiation and quantum chemical methods. The (*)OH radical was found to react by addition at diffusion-controlled rates (k = 1.1-1.7 x 10(10) dm(3) mol(-1) s(-1)), but Br(2)(*-) radical reacted by 2 orders of magnitude lower. Quantum chemical calculations at the B3LYP/6-31+G(d,p) level of theory have shown that the (C2-OH)(*), (C11-OH)(*), and (C10-OH)(*) adducts of the indole chalcones and the (C7-OH)(*) and (C8-OH)(*) adducts of the hydroxy benzenoid chalcones are more stable with DeltaH = -39 to -28 kcal mol(-1) and DeltaG = -32 to -19 kcal mol(-1). This suggests that (*)OH addition to the alpha,beta-unsaturated bond is a major reaction channel in both types of chalcones and is barrierless. The stability and lack of dehydration of the (*)OH adducts arise from two factors: strong frontier orbital interaction due to the low energy gap between interacting orbitals and the negligible Coulombic repulsion due to small absolute values of Mulliken charges. The transient absorption spectrum measured in the (*)OH radical reaction with all the indole chalcone derivatives exhibited a maximum at 390 nm, which is in excellent agreement with the computed value (394 nm). The formation of three phenolic products under steady-state radiolysis is in line with the three stable (*)OH adducts predicted by theory. Independent of the substituent, identical spectra (lambda(max) = 330-360 and approximately 580 nm) were obtained on one-electron oxidation of the three indole chalcones. MO calculations predict the deprotonation from the -NH group is more efficient than from the substituent due to the larger electron density on the N1 atom forming the chalcone indolyl radical. Its reduction potential was determined to be 0.56 V from the ABTS(*-)/ABTS(2-) couple. In benzenoid chalcones, the (*)OH adduct spectrum is characterized by a peak at 270 nm and a broad maximum centered in the range 430-450 nm with an intense bleaching at 340 nm. The spectrum formed by electron transfer in these derivatives with lambda(max) = 280 and 380 nm (epsilon(280) = 5000 dm(3) mol(-1) cm(-1) and epsilon(380) = 700 dm(3) mol(-1) cm(-1)) was assigned to its phenoxyl radical. Our pulse radiolysis experiments in combination with quantum chemical calculations demonstrate that chalcones are efficient scavengers of damaging oxyl radicals.

Induction of apoptosis and cell cycle arrest in L-1210 murine lymphoblastic leukaemia cells by (2E)-3-(2-naphthyl)-1-(3'-methoxy-4'-hydroxy-phenyl)-2-propen-1-one.

PubMed

Pedrini, Fernanda Spezia; Chiaradia, Louise Domeneghini; Licínio, Marley Aparecida; de Moraes, Ana Carolina Rabello; Curta, Juliana Costa; Costa, Aline; Mascarello, Alessandra; Creczinsky-Pasa, Tânia Beatriz; Nunes, Ricardo José; Yunes, Rosendo Augusto; Santos-Silva, Maria Cláudia

2010-09-01

New compounds with biological targets and less cytotoxicity to normal cells are necessary for cancer therapy. In this work ten synthetic chalcones derived from 2-naphtaldehyde were evaluated for their cytotoxic effect in murine acute lymphoblastic leukemia cells L-1210. A series of ten chalcones derived from 2-naphtaldehyde and corresponding acetophenones were prepared by aldolic condensation, using methanol as solvent under basic conditions, at room temperature for 24 h. The cell viability was determined by MTT colorimeter method. The cell cycle phase analysis was carried out by flow cytometry after propidium iodide staining. The apoptosis induction was assessed by exposure to phosphatidylserine (ANNEXIN V-FITC). Cytometric analysis was performed to evaluate the expression of p53, Bcl-2 and Bax protein. The caspase-3 expression was studied by immunoblotting analysis. A preliminary screening of a series of ten chalcones derived from 2-naphtaldehyde showed that chalcone 8, (2E)-3-(2-naphtyl)-1-(3'-methoxy-4'-hydroxy-phenyl)-2-propen-1-one, had the highest cytotoxic effect (IC50 of 54 microM), but not in normal human lymphocytes. To better understand the cytotoxic mechanism of chalcone 8, its effect on cell cycle and apoptosis was assessed. Our results showed that chalcone 8 caused cell cycle arrest in the G2/M phase and a significant increase in the proportion of cells in the subG0/G1 phase. Our results also demonstrated that chalcone 8 promoted a modification in Bax:Bcl-2 ratio and increased p53 expression and caspase-3 activation. The studied chalcone 8 has cytotoxic effect against L-1210 lymphoblastic leukaemic cells, and this effect is associated with increase of p-53 and Bax expression.

Chalcones isolated from Angelica keiskei inhibit cysteine proteases of SARS-CoV.

PubMed

Park, Ji-Young; Ko, Jin-A; Kim, Dae Wook; Kim, Young Min; Kwon, Hyung-Jun; Jeong, Hyung Jae; Kim, Cha Young; Park, Ki Hun; Lee, Woo Song; Ryu, Young Bae

2016-01-01

Two viral proteases of severe acute respiratory syndrome coronavirus (SARS-CoV), a chymotrypsin-like protease (3CL(pro)) and a papain-like protease (PL(pro)) are attractive targets for the development of anti-SARS drugs. In this study, nine alkylated chalcones (1-9) and four coumarins (10-13) were isolated from Angelica keiskei, and the inhibitory activities of these constituents against SARS-CoV proteases (3CL(pro) and PL(pro)) were determined (cell-free/based). Of the isolated alkylated chalcones, chalcone 6, containing the perhydroxyl group, exhibited the most potent 3CL(pro) and PL(pro) inhibitory activity with IC50 values of 11.4 and 1.2 µM. Our detailed protein-inhibitor mechanistic analysis of these species indicated that the chalcones exhibited competitive inhibition characteristics to the SARS-CoV 3CL(pro), whereas noncompetitive inhibition was observed with the SARS-CoV PL(pro).

Antiplasmodial dimeric chalcone derivatives from the roots of Uvaria siamensis.

PubMed

Salae, Abdul-Wahab; Chairerk, Orapan; Sukkoet, Piyanut; Chairat, Therdsak; Prawat, Uma; Tuntiwachwuttikul, Pittaya; Chalermglin, Piya; Ruchirawat, Somsak

2017-03-01

Four dimeric chalcone derivatives, 8″,9″-dihydrowelwitschin H, uvarins A-C, a naphthalene derivative, 2-hydroxy-3-methoxy-6-(4'- hydroxyphenyl)naphthalene, and the known dimeric chalcones, dependensin and welwitschin E, flavonoids, a cyclohexane oxide derivative, an aromatic aldehyde were isolated from the roots of Uvaria siamensis (Annonaceae). The structures of the compounds were elucidated by spectroscopic analysis, as well as by comparison with literature data. The isolated compounds with a sufficient amount for biological assays were evaluated for their antimalarial, antimycobacterial, and cytotoxic activities. The dimeric chalcones 8″,9″-dihydrowelwitschin H, uvarins B and C, dependensin and welwitschin E showed strong antiplasmodial activity with IC 50 values of 3.10, 3.02, 3.09, 4.21 and 3.99 μg/mL, respectively. A possible biosynthesis pathway of the dimeric chalcones is discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

Synthesis, crystal growth and studies on non-linear optical property of new chalcones

NASA Astrophysics Data System (ADS)

Sarojini, B. K.; Narayana, B.; Ashalatha, B. V.; Indira, J.; Lobo, K. G.

2006-09-01

The synthesis, crystal growth and non-linear optical (NLO) property of new chalcone derivatives are reported. 4-Propyloxy and 4-butoxy benzaldehydes were made to under go Claisen-Schmidt condensation with 4-methoxy, 4-nitro and 4-phenoxy acetophenones to form corresponding chalcones. The newly synthesized compounds were characterized by analytical and spectral data. The Second harmonic generation (SHG) efficiency of these compounds was measured by powder technique using Nd:YAG laser. Among tested compounds three chalcones showed NLO property. The chalcone 1-(4-methoxyphenyl)-3-(4-propyloxy phenyl)-2-propen-1-one exhibited SHG conversion efficiency 2.7 times that of urea. The bulk crystal of 1-(4-methoxyphenyl)-3-(4-butoxyphenyl)-2-propen-1-one (crystal size 65×28×15 mm 3) was grown by slow-evaporation technique from acetone. Microhardness of the crystal was tested by Vicker's microhardness method.

Two new chalcone glycosides from the stems of Entada phaseoloides.

PubMed

Zhao, Zhong-xiang; Jin, Jing; Lin, Chao-zhan; Zhu, Chen-chen; Liu, Yi-ming; Lin, Ai-hua; Liu, Ying-xiang; Zhang, Li; Luo, Hua-feng

2011-10-01

Two new chalcone glycosides 4'-O-(6″-O-galloyl-β-d-glucopyranosyl)-2',4-dihydroxychalcone (1) and 4'-O-(6″-O-galloyl-β-d-glucopyranosyl)-2'-hydroxy-4-methoxychalcone (2) together with one known chalcone glycoside 4'-O-β-d-glucopyranosyl-2'-hydroxy-4-methoxychalcone (3) were isolated from the stems of Entada phaseoloides. The structures of the new compounds were elucidated on the basis of extensive spectroscopic analysis, including HSQC, HMBC, (1)H-(1)H COSY, and chemical evidences. This is the first report of chalcone-type compounds isolated from the genus Entada. Copyright © 2011 Elsevier B.V. All rights reserved.

Synthesis and evaluation of novel prenylated chalcone derivatives as anti-leishmanial and anti-trypanosomal compounds.

PubMed

Passalacqua, Thais Gaban; Dutra, Luiz Antonio; de Almeida, Letícia; Velásquez, Angela Maria Arenas; Torres, Fabio Aurelio Esteves; Yamasaki, Paulo Renato; dos Santos, Mariana Bastos; Regasini, Luis Octavio; Michels, Paul A M; Bolzani, Vanderlan da Silva; Graminha, Marcia A S

2015-08-15

Chalcones form a class of compounds that belong to the flavonoid family and are widely distributed in plants. Their simple structure and the ease of preparation make chalcones attractive scaffolds for the synthesis of a large number of derivatives enabling the evaluation of the effects of different functional groups on biological activities. In this Letter, we report the successful synthesis of a series of novel prenylated chalcones via Claisen-Schmidt condensation and the evaluation of their effect on the viability of the Trypanosomatidae parasites Leishmania amazonensis, Leishmania infantum and Trypanosoma cruzi. Copyright © 2015 Elsevier Ltd. All rights reserved.

Ferrocenyl chalcone difluoridoborates inhibit HIV-1 integrase and display low activity towards cancer and endothelial cells.

PubMed

Monserrat, Jean-Philippe; Al-Safi, Rasha I; Tiwari, Keshri Nath; Quentin, Lionel; Chabot, Guy G; Vessières, Anne; Jaouen, Gérard; Neamati, Nouri; Hillard, Elizabeth A

2011-10-15

We report here the discovery of a potent series of HIV-1 integrase (IN) inhibitors based on the ferrocenyl chalcone difluoridoborate structure. Ten new compounds have been synthesized and were generally found to have similar inhibitory activities against the IN 3' processing and strand transfer (ST) processes. IC(50) values were found to be in the low micromolar range, and significantly lower than those found for the non-coordinated ferrocenyl chalcones and other ferrocene molecules. The ferrocenyl chalcone difluoridoborates furthermore exhibited low cytotoxicity against cancer cells and low morphological activity against epithelial cells. Copyright © 2011 Elsevier Ltd. All rights reserved.

[Kinetics of the bacteriostatic activity of natural and synthetic chalcones on a strain of Staphylococcus aureus].

PubMed

Pappano, N B; Puig de Centorbi, O; Debattista, N B; Calleri de Milan, C; Borkowski, E J; Ferretti, F H

1985-01-01

The bacteriostatic action exerted by natural chalcones (2',4'-dihydroxychalcone and 2'-hydroxy-4'-methoxychalcone) and by synthetic chalcones (chalcone, 2'-hydroxychalcone, 2'4-dihydroxychalcone and 2'-hydroxy-4-methoxychalcone) on Staphylococcus aureus (ATCC 25 923 Strain) was investigated. In addition, the influence of the concentration, nature and position of the substituents of the mentioned drugs on the specific growth rate of the germ was determined. Qualitative tests made on nutritive agar plates showed the inhibitory action of chalcone and its dihydroxyl derivatives. Quantitative experiments were made in nutritive broth at 33 degrees C, with permanent stirring (200 rpm), measuring the microbial growth by turbidimetry at 720 nm. The results distinguish the strong bacteriostatic effect of 2',4'-dihydroxychalcone and 2',4-dihydroxychalcone, which at low concentrations caused complete inhibition of microorganism growth, from the other chalcones studies which only reduced the up to a limiting value. The presence of an hydroxyl group in the A or B ring of 2'-hydroxychalcone increases its bacteriostatic activity, being this effect stronger at position 4' (ring A) than at position 4 (ring B). The introduction of a methoxy group into the 2'-hydroxychalcone structure causes a decrease of its inhibitory power.

Synthesis and anti-cancer activity evaluation of novel prenylated and geranylated chalcone natural products and their analogs.

PubMed

Wang, Hao-Meng; Zhang, Li; Liu, Jiang; Yang, Zhao-Liang; Zhao, Hong-Ye; Yang, Yao; Shen, Di; Lu, Kui; Fan, Zhen-Chuan; Yao, Qing-Wei; Zhang, Yong-Min; Teng, Yu-Ou; Peng, Yu

2015-03-06

Four natural chalcones bearing prenyl or geranyl groups, i.e., bavachalcone (1a), xanthoangelol (1b), isobavachalcone (1c), and isoxanthoangelol (1d) were synthesized by using a regio-selective iodination and the Suzuki coupling reaction as key steps. The first total synthesis of isoxanthoangelol (1d) was achieved in 36% overall yield. A series of diprenylated and digeranylated chalcone analogs were also synthesized by alkylation, regio-selective iodination, aldol condensation, Suzuki coupling and [1,3]-sigmatropic rearrangement. The structures of the 11 new derivatives were confirmed by (1)H NMR, (13)C NMR and HRMS. The anticancer activity of these new chalcone derivatives against human tumor cell line K562 were evaluated by MTT assay in vitro. SAR studies suggested that the 5'-prenylation/geranylation of the chalcones significantly enhance their cytotoxic activity. Among them, Bavachalcone (1a) displayed the most potent cytotoxic activity against K562 with IC50 value of 2.7 μM. The morphology changes and annexin-V/PI staining studies suggested that those chalcone derivatives inhibited the proliferation of K562 cells by inducing apoptosis. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Structure-activity relationship studies of chalcone leading to 3-hydroxy-4,3',4',5'-tetramethoxychalcone and its analogues as potent nuclear factor kappaB inhibitors and their anticancer activities.

PubMed

Srinivasan, Balasubramanian; Johnson, Thomas E; Lad, Rahul; Xing, Chengguo

2009-11-26

Chalcone is a privileged structure, demonstrating promising anti-inflammatory and anticancer activities. One potential mechanism is to suppress nuclear factor kappa B (NF-kappaB) activation. The structures of chalcone-based NF-kappaB inhibitors vary significantly that there is minimum information about their structure-activity relationships (SAR). This study aims to establish SAR of chalcone-based compounds to NF-kappaB inhibition, to explore the feasibility of developing simple chalcone-based potent NF-kappaB inhibitors, and to evaluate their anticancer activities. Three series of chalcones were synthesized in one to three steps with the key step being aldol condensation. These candidates demonstrated a wide range of NF-kappaB inhibitory activities, some of low micromolar potency, establishing that structural complexity is not required for NF-kappaB inhibition. Lead compounds also demonstrate potent cytotoxicity against lung cancer cells. Their cytotoxicities correlate moderately well with their NF-kappaB inhibitory activities, suggesting that suppressing NF-kappaB activation is likely responsible for at least some of the cytotoxicities. One lead compound effectively inhibits lung tumor growth with no signs of adverse side effects.

Osteogenic potential of a chalcone in a critical-size defect in rat calvaria bone.

PubMed

Ortolan, Xana Raquel; Fenner, Bruna Proiss; Mezadri, Telmo José; Tames, David Rivero; Corrêa, Rogério; de Campos Buzzi, Fátima

2014-07-01

This study describes the bone formation stimulated by the application of a type of chalcone to critical-size defects in rat calvarial bone. Sixty female Wistar rats were divided into 6 groups of 10 animals per group: control (no treatment), vehicle (vaseline) and the chalcone (1-phenyl-3-(4-chlorophenyl)-2-propen-1-one) suspended in vaseline at 10%. A critical-size defect of 5 mm was prepared using a trephine in the calvarial bone, after which the treatment was applied, in a single dose, according to the experimental group. The samples were evaluated macroscopically using ImageJ software, and histologically 30 and 45 days after surgery. At 30 days after surgery, there was significant bone formation (p < 0.05) in the groups treated with chalcone, compared with the other groups. Many active osteoblasts were observed adjacent to the borders of the newly formed bone tissue. 45 days after surgery in the chalcone group, the surgical defects showed complete bone closure. The results of this study suggest that chalcone has significant potential to induce the formation of new bone. Copyright © 2013 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Chalcone-Induced Apoptosis through Caspase-Dependent Intrinsic Pathways in Human Hepatocellular Carcinoma Cells

PubMed Central

Ramirez-Tagle, Rodrigo; Escobar, Carlos A.; Romero, Valentina; Montorfano, Ignacio; Armisén, Ricardo; Borgna, Vincenzo; Jeldes, Emanuel; Pizarro, Luis; Simon, Felipe; Echeverria, Cesar

2016-01-01

Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed cancers worldwide. Chemoprevention of HCC can be achieved through the use of natural or synthetic compounds that reverse, suppress or prevent the development of cancer progression. In this study, we investigated the antiproliferative effects and the mechanism of action of two compounds, 2,3,4′-trimethoxy-2′-hydroxy-chalcone (CH1) and 3′-bromo-3,4-dimethoxy-chalcone (CH2), over human hepatoma cells (HepG2 and Huh-7) and cultured mouse hepatocytes (HepM). Cytotoxic effects were observed over the HepG2 and Huh-7, and no effects were observed over the HepM. For HepG2 cells, treated separately with each chalcone, typical apoptotic laddering and nuclear condensation were observed. Additionally, the caspases and Bcl-2 family proteins activation by using Western blotting and immunocytochemistry were studied. Caspase-8 was not activated, but caspase-3 and -9 were both activated by chalcones in HepG2 cells. Chalcones also induced reactive oxygen species (ROS) accumulation after 4, 8 and 24 h of treatment in HepG2 cells. These results suggest that apoptosis in HepG2 was induced through: (i) a caspase-dependent intrinsic pathway; and (ii) by alterations in the cellular levels of Bcl-2 family proteins, and also, that the chalcone moiety could be a potent candidate as novel anticancer agents acting on human hepatomas. PMID:26907262

Monoamine oxidase inhibitory activities of heterocyclic chalcones.

PubMed

Minders, Corné; Petzer, Jacobus P; Petzer, Anél; Lourens, Anna C U

2015-11-15

Studies have shown that natural and synthetic chalcones (1,3-diphenyl-2-propen-1-ones) possess monoamine oxidase (MAO) inhibition activities. Of particular importance to the present study is a report that a series of furanochalcones acts as MAO-B selective inhibitors. Since the effect of heterocyclic substitution, other than furan (and more recently thiophene, piperidine and quinoline) on the MAO inhibitory properties of the chalcone scaffold remains unexplored, the aim of this study was to synthesise and evaluate further heterocyclic chalcone analogues as inhibitors of the human MAOs. For this purpose, heterocyclic chalcone analogues that incorporate pyrrole, 5-methylthiophene, 5-chlorothiophene and 6-methoxypyridine substitution were examined. Seven of the nine synthesised compounds exhibited IC50 values <1 μM for the inhibition of MAO-B, with all compounds exhibiting higher affinities for MAO-B compared to the MAO-A isoform. The most potent MAO-B inhibitor (4h) displays an IC50 value of 0.067 μM while the most potent MAO-A inhibitor (4e) exhibits an IC50 value of 3.81 μM. It was further established that selected heterocyclic chalcones are reversible and competitive MAO inhibitors. 4h, however, may exhibit tight-binding to MAO-B, a property linked to its thiophene moiety. We conclude that high potency chalcones such as 4h represent suitable leads for the development of MAO-B inhibitors for the treatment of Parkinson's disease and possibly other neurodegenerative disorders. Copyright © 2015 Elsevier Ltd. All rights reserved.

Synthesis and biological evaluation of chalcone derivatives (mini review).

PubMed

Bukhari, Syed Nasir Abbas; Jasamai, Malina; Jantan, Ibrahim

2012-11-01

Chalcones are the principal precursors for the biosynthesis of flavonoids and isoflavonoids. A three carbon α, β-unsaturated carbonyl system constitutes chalcones. Chalcones are the condensation products of aromatic aldehyde with acetophenones in attendance of catalyst. They go through an assortment of chemical reactions and are found advantageous in synthesis of pyrazoline, isoxazole and a variety of heterocyclic compounds. In synthesizing a range of therapeutic compounds, chalcones impart key role. They have showed worth mentioning therapeutic efficacy for the treatment of various diseases. Chalcone based derivatives have gained heed since they own simple structures, and diverse pharmacological actions. A lot of methods and schemes have been reported for the synthesis of these compounds. Amongst all, Aldol condensation and Claisen-Schmidt condensation still grasp high up position. Other distinguished techniques include Suzuki reaction, Witting reaction, Friedel-Crafts acylation with cinnamoyl chloride, Photo-Fries rearrangement of phenyl cinnamates etc. These inventive techniques utilize various catalysts and reagents including SOCl(2) natural phosphate, lithium nitrate, amino grafted zeolites, zinc oxide, water, Na(2)CO(3), PEG400, silicasulfuric acid, ZrCl(4) and ionic liquid etc. The development of better techniques for the synthesis of α, β- unsaturated carbonyl compounds is still in high demand. In brief, we have explained the methods and catalysts used in the synthesis of chalcones along with their biological activities in a review form to provide information for the development of new-fangled processes targeting better yield, less reaction time and least side effects with utmost pharmacological properties.

Synthesis and evaluation of 2-benzylidene-1-tetralone derivatives for monoamine oxidase inhibitory activity.

PubMed

Amakali, Klaudia T; Legoabe, Lesetja Jan; Petzer, Anel; Petzer, Jacobus P

2018-05-01

Chalcone has been identified as a promising lead for the design of monoamine oxidase (MAO) inhibitors. This study attempted to discover potent and selective chalcone-derived MAO inhibitors by synthesising a series consisting of various cyclic chalcone derivatives. The cyclic chalcones were selected based on the possibility that their restricted structures would confer a higher degree of MAO isoform selectivity, and included the following chemical classes: 1-indanone, 1-tetralone, 1-benzosuberone, chromone, thiochromone, 4-chromanone and 4-thiochromanone. The results showed that the cyclic chalcones are in general good potency, and in most instances specific inhibitors of the human MAO-B isoform. Among these compounds, the 4-chromanone derivative was the most potent MAO-B inhibitor with an IC50 value of 0.156 µM. To further investigate the MAO inhibition of cyclic chalcones, a series of twenty-three 2-benzylidene-1-tetralone derivatives were synthesised and evaluated as MAO inhibitors. Most 2-benzylidene-1-tetralones possess good inhibitory activity and specificity for MAO-B with the most potent inhibitor displaying an IC50 value of 0.0064 µM, while the most potent MAO-A inhibitor possessed an IC50 value of 0.754 µM. This study thus shows that certain cyclic chalcones are human MAO-B inhibitors, compounds that could be suitable for the treatment of neurodegenerative disorders such as Parkinson's disease. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Cloning, functional expression, and characterization of a chalcone 3-hydroxylase from Cosmos sulphureus.

PubMed

Schlangen, Karin; Miosic, Silvija; Thill, Jana; Halbwirth, Heidi

2010-07-01

A chalcone 3-hydroxylase (CH3H) cDNA clone was isolated and characterized from Cosmos sulphureus petals accumulating butein (2',3,4,4'-tetrahydroxychalcone) derivatives as yellow flower pigments. The recombinant protein catalyses the introduction of an additional hydroxyl group in the B-ring of chalcones, a reaction with high similarity to the hydroxylation of flavonoids catalysed by the well-studied flavonoid 3'-hydroxylase (F3'H). CH3H shows high specificity for chalcones, but a low F3'H activity was also detected. By contrast, the common F3'H from C. sulphureus does not accept chalcones as substrates and is therefore unlikely to be involved in the creation of the B-ring hydroxylation pattern of the yellow flower pigments. CH3H was primarily expressed in young buds, the main tissue for chalcone pigment formation. Expression levels in open flowers and 3-d-old seedlings were lower and almost no CH3H expression was observed in leaves. F3'H, in contrast, showed the highest expression also in buds, but comparable expression rates in all other tissues tested. Recombinant hybrid proteins constructed from CH3H and F3'H fragments demonstrated that amino acid residues at a substrate recognition site and an insertion of four amino acid residues in a putative loop region have an impact on chalcone acceptance. This is the first identification of a CH3H cDNA from any plant species.

Synthesis and in vitro antiplasmodial evaluation of 7-chloroquinoline-chalcone and 7-chloroquinoline-ferrocenylchalcone conjugates.

PubMed

Raj, Raghu; Saini, Anu; Gut, Jiri; Rosenthal, Philip J; Kumar, Vipan

2015-05-05

The manuscript describes the synthesis of novel amide tethered 7-chloroquinoline-chalcone and 7-chloroquinoline-ferrocenylchalcone bifunctional hybrids and their evaluation as antimalarial agents against W2 resistant strain of Plasmodium falciparum. The antiplasmodial activity of 7-chloroquinoline-ferrocenylchalcones was found to be less than their corresponding simple chalcone conjugates. The presence of a methoxy substituent at para position of ring B on chalcones and longer alkyl chain length markedly improved the antiplasmodial profiles of the synthesized scaffolds with the most potent of the test compound exhibiting an IC50 value of 17.8 nM. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Ab initio calculations of the absorption spectrum of chalcone

NASA Astrophysics Data System (ADS)

Oumi, Manabu; Maurice, David; Head-Gordon, Martin

1999-03-01

The excitation energies and excited states of trans-chalcone ( trans-( s-cis)-1,3-diphenylpropenone), and several related molecules ( trans-( s-cis)-3-phenylpropenal, s-cis-1-phenylpropenone, propenal, trans-( s-cis)-1-(4-hydroxyphenyl)-3-phenylpropenone, trans-( s-cis)3-(4-hydroxyphenyl)-1-phenylpropenone) have been calculated using single reference ab initio molecular orbital methods, and characterized by attachment-detachment density analysis. The results suggest assignments for the lowest three electronic transitions observed experimentally for trans-( s-cis)-chalcone in solution. The extent of localization of the electronic transitions is established by calculations on the excited states of trans-( s-cis)-3-phenylpropenal, s-cis-1-phenylpropenone and propenal, as well as analysis of the chalcone calculations. Contrary to some previous work, none of these excitations are strongly delocalized over the entire molecule. Calculated substituent shifts for the hydroxy chalcones are in qualitative agreement with experimental data, and support the localized interpretation of the main π→ π* transition.

A New Geranylated Chalcone from Andrographis lobelioides.

PubMed

Sumalatha, Manne; Rammohan, Aluru; Gunasekar, Duvvuru; Deville, Alexandre; Bodo, Bernard

2016-01-01

A new O-geranylated chalcone, 2'-hydroxy-2-methoxy-4'-O-[(E)-3,7-dimethyl-2,6-octadienyl] chalcone (1), together with three known flavones, 5-hydroxy-7,2'-dimethoxyflavone (2), skullcapflavone I (3) and echioidin (4), were isolated from the leaves of Andrographis lobelioides. The structure of 1 and the known compounds (2-4) were achieved by extensive 1D and 2D NMR spectral and chemical studies.

Methoxyphenyl chalcone sensitizes aggressive epithelial cancer to cisplatin through apoptosis induction and cancer stem cell eradication.

PubMed

Su, Yu-Kai; Huang, Wen-Chien; Lee, Wei-Hwa; Bamodu, Oluwaseun Adebayo; Zucha, Muhammad Ary; Astuti, Indwiani; Suwito, Heri; Yeh, Chi-Tai; Lin, Chien-Min

2017-05-01

Current standard chemotherapy for late stage ovarian cancer is found unsuccessful due to relapse after completing the regimens. After completing platinum-based chemotherapy, 70% of patients develop relapse and resistance. Recent evidence proves ovarian cancer stem cells as the source of resistance. Therefore, treatment strategy to target both cancer stem cells and normal stem cells is essential. In this study, we developed a novel chalcone derivative as novel drug candidate for ovarian cancer treatment. We found that methoxyphenyl chalcone was effective to eliminate ovarian cancer cells when given either as monotherapy or in combination with cisplatin. We found that cell viability of ovarian cancer cells was decreased through apoptosis induction. Dephosphorylation of Bcl2-associated agonist of cell death protein was increased after methoxyphenyl chalcone treatment that led to activation of caspases. Interestingly, this drug also worked as a G2/M checkpoint modulator with alternative ways of DNA damage signal-evoking potential that might work to increase response after cisplatin treatment. In addition, methoxyphenyl chalcone was able to suppress autophagic flux and stemness regulator in ovarian spheroids that decreased their survival. Therefore, combination of methoxyphenyl chalcone and cisplatin showed synergistic effects. Taken together, we believe that our novel compound is a promising novel therapeutic agent for effective clinical treatment of ovarian cancer.

Targeting Death Receptor TRAIL-R2 by Chalcones for TRAIL-Induced Apoptosis in Cancer Cells

PubMed Central

Szliszka, Ewelina; Jaworska, Dagmara; Kłósek, Małgorzata; Czuba, Zenon P.; Król, Wojciech

2012-01-01

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in cancer cells without toxicity to normal cells. TRAIL binds to death receptors, TRAIL-R1 (DR4) and TRAIL-R2 (DR5) expressed on cancer cell surface and activates apoptotic pathways. Endogenous TRAIL plays an important role in immune surveillance and defense against cancer cells. However, as more tumor cells are reported to be resistant to TRAIL mediated death, it is important to search for and develop new strategies to overcome this resistance. Chalcones can sensitize cancer cells to TRAIL-induced apoptosis. We examined the cytotoxic and apoptotic effects of TRAIL in combination with four chalcones: chalcone, isobavachalcone, licochalcone A and xanthohumol on HeLa cancer cells. The cytotoxicity was measured by MTT and LDH assays. The apoptosis was detected using annexin V-FITC staining by flow cytometry and fluorescence microscopy. Death receptor expression was analyzed using flow cytometry. The decreased expression of death receptors in cancer cells may be the cause of TRAIL-resistance. Chalcones enhance TRAIL-induced apoptosis in HeLa cells through increased expression of TRAIL-R2. Our study has indicated that chalcones augment the antitumor activity of TRAIL and confirm their cancer chemopreventive properties. PMID:23203129

Study of the antibacterial and antifungal activities of synthetic benzyl bromides, ketones, and corresponding chalcone derivatives.

PubMed

Shakhatreh, Muhamad Ali K; Al-Smadi, Mousa L; Khabour, Omar F; Shuaibu, Fatima A; Hussein, Emad I; Alzoubi, Karem H

2016-01-01

Several applications of chalcones and their derivatives encouraged researchers to increase their synthesis as an alternative for the treatment of pathogenic bacterial and fungal infections. In the present study, chalcone derivatives were synthesized through cross aldol condensation reaction between 4-( N , N -dimethylamino)benzaldehyde and multiarm aromatic ketones. The multiarm aromatic ketones were synthesized through nucleophilic substitution reaction between 4-hydroxy acetophenone and benzyl bromides. The benzyl bromides, multiarm aromatic ketones, and corresponding chalcone derivatives were evaluated for their activities against eleven clinical pathogenic Gram-positive, Gram-negative bacteria, and three pathogenic fungi by the disk diffusion method. The minimum inhibitory concentration was determined by the microbroth dilution technique. The results of the present study demonstrated that benzyl bromide derivatives have strong antibacterial and antifungal properties as compared to synthetic chalcone derivatives and ketones. Benzyl bromides (1a and 1c) showed high ester activity against Gram-positive bacteria and fungi but moderate activity against Gram-negative bacteria. Therefore, these compounds may be considered as good antibacterial and antifungal drug discovery. However, substituted ketones (2a-b) as well as chalcone derivatives (3a-c) showed no activity against all the tested strains except for ketone (2c), which showed moderate activity against Candida albicans .

Study of the antibacterial and antifungal activities of synthetic benzyl bromides, ketones, and corresponding chalcone derivatives

PubMed Central

Shakhatreh, Muhamad Ali K; Al-Smadi, Mousa L; Khabour, Omar F; Shuaibu, Fatima A; Hussein, Emad I; Alzoubi, Karem H

2016-01-01

Several applications of chalcones and their derivatives encouraged researchers to increase their synthesis as an alternative for the treatment of pathogenic bacterial and fungal infections. In the present study, chalcone derivatives were synthesized through cross aldol condensation reaction between 4-(N,N-dimethylamino)benzaldehyde and multiarm aromatic ketones. The multiarm aromatic ketones were synthesized through nucleophilic substitution reaction between 4-hydroxy acetophenone and benzyl bromides. The benzyl bromides, multiarm aromatic ketones, and corresponding chalcone derivatives were evaluated for their activities against eleven clinical pathogenic Gram-positive, Gram-negative bacteria, and three pathogenic fungi by the disk diffusion method. The minimum inhibitory concentration was determined by the microbroth dilution technique. The results of the present study demonstrated that benzyl bromide derivatives have strong antibacterial and antifungal properties as compared to synthetic chalcone derivatives and ketones. Benzyl bromides (1a and 1c) showed high ester activity against Gram-positive bacteria and fungi but moderate activity against Gram-negative bacteria. Therefore, these compounds may be considered as good antibacterial and antifungal drug discovery. However, substituted ketones (2a–b) as well as chalcone derivatives (3a–c) showed no activity against all the tested strains except for ketone (2c), which showed moderate activity against Candida albicans. PMID:27877017

Effects of a herbal gel containing carvacrol and chalcones on alveolar bone resorption in rats on experimental periodontitis.

PubMed

Botelho, Marco Antonio; Rao, Vietla Satyanarayana; Montenegro, Danusa; Bandeira, Mary Anne Menezes; Fonseca, Said Gonçalves Cruz; Nogueira, Nadia Accioly Pinto; Ribeiro, Ronaldo Albuquerque; Brito, Gerly Anne Castro

2008-04-01

Carvacrol and dimeric chalcones are the respective bioactive components of Lippia sidoides and Myracrodruon urundeuva, popular medicinal plants of Northeastern Brazil with proven antimicrobial and antiinflammatory properties. Periodontal disease is associated with inflammation and microbiological proliferation, thus the study aimed to investigate the effect of a topical gel based on carvacrol and chalcones in the experimental periodontal disease (EPD) in rats. Animals were treated with carvacrol and/or chalcones gel, immediately after EPD induction, three times a day for 11 days. Appropriate controls were included in the study. Animals were weighed daily. They were killed on day 11, the mandibles dissected and alveolar bone loss was measured. The periodontium were examined at histopathology and the neutrophil influx into the gingiva was assayed using myeloperoxidase activity. The bacterial flora were assessed through culture of the gingival tissue. Alveolar bone loss was significantly (p < 0.05) inhibited by combined carvacrol and chalcones gel, compared with the vehicle and non-treated groups. The treatment with the combined gel reduced tissue lesion at histopathology, decreased myeloperoxidase activity in gingival tissue and inhibited the growth of oral microorganisms as well as the weight loss. Carvacrol and chalcones combination gel has a beneficial effect upon EPD in this model. (c) 2008 John Wiley & Sons, Ltd.

Pharmacokinetic Studies of Oxathio-Heterocycle Fused Chalcones.

PubMed

Okoniewska, Krystyna; Konieczny, Marek T; Lemke, Krzysztof; Grabowski, Tomasz

2017-02-01

Chalcone constitutes one of the most used molecular frameworks in medicinal chemistry and its derivatives exhibit a broad spectrum of biological activities. Low absolute bioavailability, poor distribution, intensive metabolism and elimination of chalcones are the main problems in designing new drugs based on their structure. One of the fundamental steps in evaluation of drug candidates is a comparative analysis of pharmacokinetic parameters. The aim of the studies was the pharmacokinetic characterization of the selected oxathio-heterocycle fused chalcones. The pharmacokinetic parameters of 19 compounds were reported. The analyzed chalcones were examined after a single intravenous administration to forty 7-week-old mature male rats of Wistar stock. Pharmacokinetic analysis was performed independently using SHAM (slopes, highest, amounts, and moments) and the two-compartment model. Basic physiochemical parameters were calculated. The bioanalytical methods were validated in terms of repeatability, linearity, accuracy, precision, and selectivity. The pharmacokinetics of the examined group of chalcones are compatible with the two-compartment model. The physicochemical characteristics of this group are quite homogeneous. The kinetics of the examined chalcones are indicative of a distribution to the tissue compartment with the predominance of a rate constant from central to peripheral compartments (k 12 ) over the rate constant from peripheral to central compartments (k 21 ). The elimination from the central compartment (k 10 ) is higher than the transfer from the central compartment to the tissues (k 10  > k 12 ) in almost all examined cases. The presented group of compounds may form a starting point for studies into drugs treating autoimmune diseases of the gastro-intestinal tract.

Second harmonic generation and crystal growth of new chalcone derivatives

NASA Astrophysics Data System (ADS)

Patil, P. S.; Dharmaprakash, S. M.; Ramakrishna, K.; Fun, Hoong-Kun; Sai Santosh Kumar, R.; Narayana Rao, D.

2007-05-01

We report on the synthesis, crystal structure and optical characterization of chalcone derivatives developed for second-order nonlinear optics. The investigation of a series of five chalcone derivatives with the second harmonic generation powder test according to Kurtz and Perry revealed that these chalcones show efficient second-order nonlinear activity. Among them, high-quality single crystals of 3-Br-4'-methoxychalcone (3BMC) were grown by solvent evaporation solution growth technique. Grown crystals were characterized by X-ray powder diffraction (XRD), laser damage threshold, UV-vis-NIR and refractive index measurement studies. Infrared spectroscopy, thermogravimetric analysis and differential thermal analysis measurements were performed to study the molecular vibration and thermal behavior of 3BMC crystal. Thermal analysis does not show any structural phase transition.

Theoretical and experimental study demonstrates kinetic control in chalcone-flavanone transformation of naphthalene derivatives

NASA Astrophysics Data System (ADS)

Gasque, Laura; Álvarez-Idaboy, J. Raul; Flores-Álamo, Marcos; Guzmán-Méndez, Óscar; Campos-Cerón, Juan M.

2018-04-01

The condensation of 1‧-hydroxy-2‧-acetonaphthone with 1- or 2-naphthaldehyde produced the corresponding stable chalcones: C1 or C2. However, the condensation product of either naphthaldehyde with 2‧-hydroxy-1‧-acetonaphthone yielded chalcones that convert to flavanones- F1 and F2- upon recrystallization. Crystal structures for C1, F1 and F2 are described. Transition state theory estimated rate constants, based on the calculated DFT M052X/6-311 + G(d,p) Gibbs Free energies, show that the rate delimiting step is the cyclization of the chalconate in protic polar solvent. The thermodynamically preferred product is always the flavanone, therefore, the yielding of one or other product is kinetically controlled.

New chalcone and dimeric chalcones with 1,4-p-benzoquinone residue from Combretum yunnanense.

PubMed

Wu, Ming-Mei; Wang, Li-Qin; Hua, Yan; Chen, Ye-Gao; Wang, Yuan-Yuan; Li, Xing-Yao; Li, Yan; Li, Ting; Yang, Xun-Yun; Tang, Zheng-Rong

2011-03-01

New chalcone and dimeric chalcones with 1,4- P-benzoquinone residue, combrequinone A (1), combrequinone B (2), and combrequinone C (3), along with three known compounds (4-6), were isolated from the ethanolic extract of the stems and leaves of Combretum yunnanense, and their structures were determined by spectroscopic analysis. Compounds 1-3 were evaluated for in vitro cytotoxicity against five human cancer cell lines: HL-60, SMMC-7721, A-549, MCF-7, and SW480. Compounds 1, 2 and 3 were found to be most potent against HL-60 acute leukemia cells, with IC₅₀ values of 4.63, 4.07, and 1.26 µM, respectively. © Georg Thieme Verlag KG Stuttgart · New York.

Synthesis of novel substituted 1,3-diaryl propenone derivatives and their antimalarial activity in vitro.

PubMed

Mishra, Nidhi; Arora, Preeti; Kumar, Brajesh; Mishra, Lokesh C; Bhattacharya, Amit; Awasthi, Satish K; Bhasin, Virendra K

2008-07-01

The synthesis of novel 1,3-diaryl propenone derivatives and their antimalarial activity in vitro against asexual blood stages of human malaria parasite, Plasmodium falciparum, are described. Chalcone derivatives were prepared via Claisen-Schmidt condensation of substituted aldehydes with substituted methyl ketones. Antiplasmodial IC(50) (half maximal inhibitory concentration) activity of these compounds ranged between 1.5 and 12.3 microg/ml. The chloro-series, 1,2,4-triazole substituted chalcone was found to be the most effective in inhibiting the growth of P. falciparum in vitro while pyrrole and benzotriazole substituted chalcones showed relatively less inhibitory activity. This is the first report on antiplasmodial activity of chalcones with azoles on acetophenone ring.

Current prospects of synthetic curcumin analogs and chalcone derivatives against mycobacterium tuberculosis.

PubMed

Bukhari, Syed Nasir Abbas; Franzblau, Scott G; Jantan, Ibrahim; Jasamai, Malina

2013-11-01

Tuberculosis, caused by Mycobacterium tuberculosis, is amongst the foremost infectious diseases. Treatment of tuberculosis is a complex process due to various factors including a patient's inability to persevere with a combined treatment regimen, the difficulty in eradicating the infection in immune-suppressed patients, and multidrug resistance (MDR). Extensive research circumscribing molecules to counteract this disease has led to the identification of many inhibitory small molecules. Among these are chalcone derivatives along with curcumin analogs. In this review article, we summarize the reported literature regarding anti tubercular activity of chalcone derivatives and synthetic curcumin analogs. Our goal is to provide an analysis of research to date in order to facilitate the synthesis of superior antitubercular chalcone derivatives and curcumin analogs.

Inhibition of sortase A by chalcone prevents Listeria monocytogenes infection.

PubMed

Li, Hongen; Chen, Yutao; Zhang, Bing; Niu, Xiaodi; Song, Meng; Luo, Zhaoqing; Lu, Gejin; Liu, Bowen; Zhao, Xiaoran; Wang, Jianfeng; Deng, Xuming

2016-04-15

The critical role of sortase A in gram-positive bacterial pathogenicity makes this protein a good potential target for antimicrobial therapy. In this study, we report for the first time the crystal structure of Listeria monocytogenes sortase A and identify the active sites that mediate its transpeptidase activity. We also used a sortase A (SrtA) enzyme activity inhibition assay, simulation, and isothermal titration calorimetry analysis to discover that chalcone, an agent with little anti-L. monocytogenes activity, could significantly inhibit sortase A activity with an IC50 of 28.41 ± 5.34 μM by occupying the active site of SrtA. The addition of chalcone to a co-culture of L. monocytogenes and Caco-2 cells significantly inhibited bacterial entry into the cells and L. monocytogenes-mediated cytotoxicity. Additionally, chalcone treatment decreased the mortality of infected mice, the bacterial burden in target organs, and the pathological damage to L. monocytogenes-infected mice. In conclusion, these findings suggest that chalcone is a promising candidate for the development of treatment against L. monocytogenes infection. Copyright © 2016 Elsevier Inc. All rights reserved.

Synthesis and anti Methicillin resistant Staphylococcus aureus activity of substituted chalcones alone and in combination with non-beta-lactam antibiotics.

PubMed

Tran, Thanh-Dao; Do, Tuong-Ha; Tran, Ngoc-Chau; Ngo, Trieu-Du; Huynh, Thi-Ngoc-Phuong; Tran, Cat-Dong; Thai, Khac-Minh

2012-07-15

A total of 30 chalcone analogues was synthesized via a base catalyzed Claisen Schmidt condensation and screened for their in vitro antibacterial activity against Methicillin-sensitive Staphylococcus aureus (MSSA) and Methicillin-resistant Staphylococcus aureus (MRSA) alone or in combination with non beta-lactam antibiotics namely ciprofloxacin, chloramphenicol, erythromycin, vancomycin, doxycycline and gentamicin. In the checkerboard technique, fractional inhibitory concentration indices (FICI) show that the following combinations like ciprofloxacin with 25 (4'-bromo-2-hydroxychalcone); doxycycline with 21 (4-hydroxychalcone); doxycycline with 25; and doxycycline with 4 (2',2-dihydroxychalcone) were synergistic against MRSA. In term SAR study, the relationship between chalcone structure and their antibacterial activity against S. aureus and synergy with tested antibiotics were discussed. Possible mechanisms for antibacterial activity of chalcones alone as well as the synergistic effect in combinations were proposed by molecular modeling studies, respectively. Combinations of chalcones with conventional antibiotics could be an effective alternative in the treatment of infection caused by MRSA. Copyright © 2012 Elsevier Ltd. All rights reserved.

17O NMR studies on 4- and 4'-substituted chalcones and p-substituted β-nitrostyrenes

NASA Astrophysics Data System (ADS)

Boykin, D. W.; Baumstark, A. L.; Balakrishnan, P.; Perjéssy, A.; Hrnc˜iar, P.

The 17O NMR chemical shift data for 17O-enriched 4- and 4'-chalcones in toluene at 90°C and for p-substituted β-nitrostyrenes (natural abundance) in acetonitrile at 70°C are reported. The SCS (substituent chemical shift) range for the 4-chalcones p-CH 3O to p-NO 2 is 16.3 ppm; the range for the 4'-chalcones p-CH 3O to p-NO 2 is 32.4 ppm. The SCS range for the p-substituted-β-nitrostyrenes p-CH 3O to p-NO 2 is 13.2 ppm. The data for the three series gave good correlations with σ + constants, while the Dual Substitutent Parameter treatment only slightly improved the correlations using σ R+ constants. Plots of the 17O chemical shifts for both 4- and 4'-chalcones with 17O data for acetophenones and correlation of 17O chemical shift data for the β-nitrostyrenes with that of nitrobenzenes gave good correlations. Plots of the 17O data for all the three series with their respective functional group stretching frequencies gave fair correlations.

Design, Synthesis and Biological Evaluation of Oxindole-Based Chalcones as Small-Molecule Inhibitors of Melanogenic Tyrosinase.

PubMed

Suthar, Sharad Kumar; Bansal, Sumit; Narkhede, Niteen; Guleria, Manju; Alex, Angel Treasa; Joseph, Alex

2017-01-01

The enzyme tyrosinase regulates melanogenesis and skin hyperpigmentation by converting L-3,4-dihydroxyphenylalanine (L-DOPA) into dopaquinone, a key step in the melanin biosynthesis. The present work deals with design and synthesis of various oxindole-based chalcones as monophenolase and diphenolase activity inhibitors of tyrosinase. Among the screened compounds, 4-hydroxy-3-methoxybenzylidene moiety bearing chalcone (7) prepared by one pot reaction of oxindole and vanillin displayed the highest activity against tyrosinase with IC 50 s of 63.37 and 59.71 µM in monophenolase and diphenolase activity assays, respectively. In molecular docking studies, chalcone 7 also showed the highest binding affinity towards the enzyme tyrosinase while exhibiting the lowest estimated free energy of binding, among all the ligands docked.

A comprehensive review of chalcone derivatives as antileishmanial agents.

PubMed

de Mello, Marcos Vinícius Palmeira; Abrahim-Vieira, Barbara de Azevedo; Domingos, Thaisa Francielle Souza; de Jesus, Jessica Barbosa; de Sousa, Ana Carolina Corrêa; Rodrigues, Carlos Rangel; Souza, Alessandra M Teles de

2018-04-25

Leishmaniasis is a group of infectious neglected tropical diseases caused by more than 20 pathogenic species of Leishmania sp. Due to the limitations of the current treatments available, chalcone moiety has been drawn with a lot of attention due to the simple chemistry and synthesis, being reported with antileishmanial activity in particular against amastigote form. This review aims to provide an overview towards antileishmanial activity of chalcones derivatives against amastigote form for Leishmania major, L. amazonensis, L. panamensis, L. donovani and L. infantum as well as their structure-activity relationship (SAR), molecular targets and in silico ADMET evaluation. In this way, it is expected that this review may support the research and development of new promising chalcones candidates a leishmanicidal drugs. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Biological evaluation of indolizine-chalcone hybrids as new anticancer agents.

PubMed

Park, Sujin; Kim, Eun Hye; Kim, Jinwoo; Kim, Seong Hwan; Kim, Ikyon

2018-01-20

A new chemical space was explored based on an indolizine-chalcone hybrid, which was readily accessible by base-mediated aldol condensation of indolizine bearing a 7-acetyl group with various (hetero)aromatic aldehydes. Their anticancer effect was evaluated, revealing that indolizine-chalcone hybrids with 3,5-dimethoxyphenyl group (4h) or the halogen at the meta position (4j and 4l) could have the potential to induce the caspase-dependent apoptosis of human lymphoma cells. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

In silico modeling and synthesis of phenyl and thienyl analogs of chalcones for potential leads as anti-bacterial agents

NASA Astrophysics Data System (ADS)

Kar, Swayamsiddha; Mishra, Rohit Kumar; Pathak, Ashutosh; Dikshit, Anupam; Golakoti, Nageswara Rao

2018-03-01

In the recent times, the common diseases like food poisoning, pneumonia, diarrhea etc. have been observed to be drug resistant. The present study deals with the synthesis of known chalcone derivatives using the Claisen-Schmidt condensation and further characterization using UV-vis, IR, 1H NMR, 13C NMR and mass spectrometry. These derivatives were first simulated for their anti-bacterial efficacy in silico and consequently confirmed in vitro to confirm the findings. One of the chalcones, 4-NDM-2‧-HC showed excellent in-vitro antibacterial activity with an IC90 0.43 mg/mL against Vibrio cholerae as compared to commercially available antibiotic gentamicin as the standard. Further, all these tested chalcone derivatives fulfill Lipinski's parameters and show tremendous drug likeness score, confirming their potential as antibacterial leads.

Synthesis, crystal structure and antimicrobial potential of some fluorinated chalcone-1,2,3-triazole conjugates.

PubMed

Yadav, Pinki; Lal, Kashmiri; Kumar, Lokesh; Kumar, Ashwani; Kumar, Anil; Paul, Avijit K; Kumar, Rajnish

2018-06-02

A simple and green synthesis of some fluorinated chalcone-triazole hybrids from propargylated chalcones and organic azides catalyzed by cellulose supported copper nanoparticles click reaction is reported. All the synthesized compounds were well characterized by various analytical and spectroscopic methods. The X-rays crystallographic study of compounds 6k revealed the self assembling properties. The antimicrobial screening results of all the synthesized compounds revealed that most of the triazole hybrids exhibited significant efficacy against tested bacterial and fungal strains. The activity results showed the synergistic effect of biological activity when two pharmacophoric units, i.e. chalcone and 1,2,3-triazole are conjugated. Further, docking simulation of the most active compounds 6p into Escherichia coli topoisomerase II DNA Gyrase B was also carried out. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Nematicidal activity of acetophenones and chalcones against Meloidogyne incognita and structure-activity considerations.

PubMed

Caboni, Pierluigi; Aissani, Nadhem; Demurtas, Monica; Ntalli, Nikoletta; Onnis, Valentina

2016-01-01

With the ultimate goal of identifying new compounds active against root-knot nematodes, a set of 14 substituted chalcones were synthesised, starting from acetophenones. These chalcones and various acetophenones were tested in vitro against Meloidogyne incognita. The most potent acetophenones were 4-nitroacetophenone and 4-iodoacetophenone, with EC(50/24 h) values of 12 ± 5 and 15 ± 4 mg L(-1) respectively, somewhat weaker than that of the chemical control fosthiazate in our previous experiments (EC(50/24 h) 0.4 ± 0.3 mg L(-1)). When we converted the acetophenones to chalcones, the nematicidal activity differed, based on their substitution pattern. The condensation of 4-nitroacetophenone with 2,4,6-trihydroxybenzaldehyde to give the corresponding chalcone (E)-1-(4-nitrophenyl)-3-(2,4,6-trihydroxyphenyl)prop-2-en-1-one led to a slight reduction in activity (EC(50/24 h) value 25 ± 17 mg L(-1)). Moreover, (E)-3-(2-hydroxy-5-iodophenyl)-1-(4-methoxyphenyl)prop-2-en-1-one showed better activity (EC(50/24) h value 26 ± 15 mg L(-1)) than 4-methoxyacetophenone (EC(50/24 h) value 43 ± 10 mg L(-1)). Acetophenones and chalcones may represent good leads in the discovery of new nematicidal compounds and may have potential use in crop management as active ingredients. © 2015 Society of Chemical Industry.

Computer-aided discovery of two novel chalcone-like compounds active and selective against Leishmania infantum.

PubMed

Gomes, Marcelo N; Alcântara, Laura M; Neves, Bruno J; Melo-Filho, Cleber C; Freitas-Junior, Lucio H; Moraes, Carolina B; Ma, Rui; Franzblau, Scott G; Muratov, Eugene; Andrade, Carolina Horta

2017-06-01

Leishmaniasis are infectious diseases caused by parasites of genus Leishmania that affect affects 12 million people in 98 countries mainly in Africa, Asia, and Latin America. Effective treatments for this disease are urgently needed. In this study, we present a computer-aided approach to investigate a set of 32 recently synthesized chalcone and chalcone-like compounds to act as antileishmanial agents. As a result, nine most promising compounds and three potentially inactive compounds were experimentally evaluated against Leishmania infantum amastigotes and mammalian cells. Four compounds exhibited EC 50 in the range of 6.2-10.98μM. In addition, two compounds, LabMol-65 and LabMol-73, exhibited cytotoxicity in macrophages >50μM that resulted in better selectivity compared to standard drug amphotericin B. These two compounds also demonstrated low cytotoxicity and high selectivity towards Vero cells. The results of target fishing followed by homology modeling and docking studies suggest that these chalcone compounds could act in Leishmania because of their interaction with cysteine proteases, such as procathepsin L. Finally, we have provided structural recommendations for designing new antileishmanial chalcones. Copyright © 2017 Elsevier Ltd. All rights reserved.

Studies on third-order nonlinear optical properties of chalcone derivatives in polymer host

NASA Astrophysics Data System (ADS)

Shettigar, Seetharam; Umesh, G.; Chandrasekharan, K.; Sarojini, B. K.; Narayana, B.

2008-04-01

In this paper we present the experimental study of the third-order nonlinear optical properties of two chalcone derivatives, viz., 1-(4-methoxyphenyl)-3-(4-butyloxyphenyl)-prop-2-en-1-one and 1-(4-methoxyphenyl)-3-(4-propyloxyphenyl)-prop-2-en-1-one in PMMA host, with the prospective of reaching a compromise between good processability and high nonlinear optical properties. The nonlinear optical properties have been investigated by Z-scan technique using 7 ns laser pulses at 532 nm. The nonlinear refractive index, nonlinear absorption coefficient, magnitude of third-order susceptibility and the coupling factor have been determined. The values obtained are of the order of 10 -14 cm 2/W, 1 cm/GW, 10 -13 esu and 0.2, respectively. The molecular second hyperpolarizability for the chalcone derivatives in polymer is of the order of 10 -31 esu. Different guest/host concentrations have also been studied. The results suggest that the nonlinear properties of the chalcones have been improved when they are used as dopants in polymer matrix. The nonlinear parameters obtained are comparable with the reported values of II-VI compound semiconductors. Hence, these chalcons are a promising class of nonlinear optical dopant materials for optical device applications.

Semi-synthesis and NMR spectral assignments of flavonoid and chalcone derivatives.

PubMed

Kumar, Rohitesh; Lu, Yuting; Elliott, Alysha G; Kavanagh, Angela M; Cooper, Matthew A; Davis, Rohan A

2016-11-01

Previous investigations of the aerial parts of the Australian plant Eremophila microtheca and Syzygium tierneyanum resulted in the isolation of the antimicrobial flavonoid jaceosidin (4) and 2',6'-dihydroxy-4'-methoxy-3',5'-dimethyl chalcone (7), respectively. In this current study, compounds 4 and 7 were derivatized by acetylation, pivaloylation, and methylation reactions. The final products, 5,7,4'-triacetoxy jaceosidin (10), 5,7,4'-tripivaloyloxy jaceosidin (11), 5,7,4'-trimethoxy jaceosidin (12), 2',6'-diacetoxy-4'-methoxy-3',5'-dimethyl chalcone (13), 2'-hydroxy-4'-methoxy-6'-pivaloyloxy-3',5'-dimethyl chalcone (14), and 2'-hydroxy-4',6'-dimethoxy-3',5'-dimethyl chalcone (15) were all fully characterized by NMR and MS. Derivatives 10 and 13 have been previously reported but were only partially characterized. This is the first reported synthesis of 11 and 14. The natural products and their derivatives were evaluated for their antibacterial and antifungal properties, and the natural product, jaceosidin (4) and the acetylated derivative, 5,7,4'-triacetoxy jaceosidin (10), showed modest antibacterial activity (32-128 µg/ml) against Staphylococcus aureus strains. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Novel synthetic chalcones induce apoptosis in the A549 non-small cell lung cancer cells harboring a KRAS mutation.

PubMed

Wang, Yiqiang; Hedblom, Andreas; Koerner, Steffi K; Li, Mailin; Jernigan, Finith E; Wegiel, Barbara; Sun, Lijun

2016-12-01

A series of novel chalcones were synthesized by the Claisen-Schmidt condensation reaction of tetralones and 5-/6-indolecarboxaldehydes. Treatment of human lung cancer cell line harboring KRAS mutation (A549) with the chalcones induced dose-dependent apoptosis. Cell cycle analyses and Western blotting suggested the critical role of the chalcones in interrupting G2/M transition of cell cycle. SAR study demonstrated that substituent on the indole N atom significantly affects the anticancer activity of the chalcones, with methyl and ethyl providing the more active compounds (EC 50 : 110-200nM), Compound 1g was found to be >4-fold more active in the A549 cells (EC 50 : 110nM) than in prostate (PC3) or pancreatic cancer (CLR2119, PAN02) cells. Furthermore, compound 1l selectively induced apoptosis of lung cancer cells A549 (EC 50 : 0.55μM) but did not show measurable toxicity in the normal lung bronchial epithelial cells (hBEC) at doses as high as 10μM, indicating specificity towards cancer cells. Copyright © 2016 Elsevier Ltd. All rights reserved.

Chalcone Derivatives: Anti-inflammatory Potential and Molecular Targets Perspectives.

PubMed

Mahapatra, Debarshi Kar; Bharti, Sanjay Kumar; Asati, Vivek

2017-11-20

Chalcone or (E)-1,3-diphenyl-2-propene-1-one scaffold has gained considerable scientific interest in medicinal chemistry owing to its simple chemistry, ease in synthesizing a variety of derivatives and exhibiting a broad range of promising pharmacological activities by modulating several molecular targets. A number of natural and (semi-) synthetic chalcone derivatives have demonstrated admirable anti-inflammatory activity due to their inhibitory potential against various therapeutic targets like Cyclooxygenase (COX), Lipooxygenase (LOX), Interleukins (IL), Prostaglandins (PGs), Nitric Oxide Synthase (NOS), Leukotriene D4 (LTD4), Nuclear Factor-κB (NF- κB), Intracellular Cell Adhesion Molecule-1 (ICAM-1), Vascular Cell Adhesion Molecule-1 (VCAM-1), Monocyte Chemoattractant Protein-1 (MCP-1) and TLR4/MD-2, etc. The chalcone scaffold with hydroxyl, methoxyl, carboxyl, prenyl group and/or heterocyclic ring substitution like thiophene/furan/indole showed promising anti-inflammatory activity. In this review, a comprehensive study (from the year 1991 to 2016) on multi-targets of inflammatory interest, related inflammation reactions and their treatment by chalcone-based inhibitors acting on various molecular targets entailed in inflammation, Structure-Activity Relationships (SARs), Mechanism of Actions (MOAs), and patents are highlighted. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Hydroxylated chalcones with dual properties: xanthine oxidase inhibitors and radical scavengers

PubMed Central

Hofmann, Emily; Webster, Jonathan; Do, Thuy; Kline, Reid; Snider, Lindsey; Hauser, Quintin; Higginbottom, Grace; Campbell, Austin; Ma, Lili; Paula, Stefan

2016-01-01

In this study, we evaluated the abilities of a series of chalcones to inhibit the activity of the enzyme xanthine oxidase (XO) and to scavenge radicals. 20 mono- and polyhydroxylated chalcone derivatives were synthesized by Claisen-Schmidt condensation reactions and then tested for inhibitory potency against XO, a known generator of reactive oxygen species (ROS). In parallel, the ability of the synthesized chalcones to scavenge a stable radical was determined. Structure-activity relationship analysis in conjunction with molecular docking indicated that the most active XO inhibitors carried a minimum of three hydroxyl groups. Moreover, the most effective radical scavengers had two neighboring hydroxyl groups on at least one of the two phenyl rings. Since it has been proposed previously that XO inhibition and radical scavenging could be useful properties for reduction of ROS-levels in tissue, we determined the chalcones’ effects to rescue neurons subjected to ROS-induced stress created by the addition of β-amyloid peptide. Best protection was provided by chalcones that combined good inhibitory potency with high radical scavenging ability in a single molecule, an observation that points to a potential therapeutic value of this compound class. PMID:26762836

Strains for the production of flavonoids from glucose

DOEpatents

Stephanopoulos, Gregory; Santos, Christine; Koffas, Mattheos

2015-11-13

The invention relates to the production of flavonoids and flavonoid precursors in cells through recombinant expression of tyrosine ammonia lyase (TAL), 4-coumarate:CoA ligase (4CL), chalcone synthase (CHS), and chalcone isomerase (CHI).

Silver-catalyzed double-decarboxylative cross-coupling of α-keto acids with cinnamic acids in water: a strategy for the preparation of chalcones.

PubMed

Zhang, Ning; Yang, Daoshan; Wei, Wei; Yuan, Li; Nie, Fafa; Tian, Laijin; Wang, Hua

2015-03-20

A silver-catalyzed double-decarboxylative protocol has been proposed for the construction of chalcone derivatives via cascade coupling of substituted α-keto acids with cinnamic acids under the mild aqueous conditions. The developed method for constructing C-C bonds via double-decarboxylative reactions is efficient, practical, and environmentally benign by using the readily available starting materials. It should provide a promising synthesis candidate for the formation of diverse and useful chalcone derivatives in the fields of synthetic and pharmaceutical chemistry.

Inhibitory effect of chalcone derivatives on recombinant human aldose reductase.

PubMed

Iwata, S; Nagata, N; Omae, A; Yamaguchi, S; Okada, Y; Shibata, S; Okuyama, T

1999-03-01

More than fifty chalcone derivatives were synthesized to examine structure-activity relationships against human aldose reductase. Certain 2',4'-dihydroxychalcone derivatives inhibited human aldose reductase activities, and 2',4',2, 4-tetrahydroxychalcone and 2',4',2-trihydroxychalcone showed potent inhibitory activity with IC50 values of 7.4x10(-9) M and 1.6x10(-7) M, respectively. On the other hand, cis-form chalcones, which were isomerized from the original trans-forms by irradiation of daylight in methanol solution, promoted the activity of human aldose reductase.

Studies on chalcone derivatives: complex formation, thermal behavior, stability constant and antioxidant activity.

PubMed

El-Sayed, Yusif S; Gaber, M

2015-02-25

The chalcone 3-[4'-dimethylaminophenyl]-1-(2-pyridyl) prop-2-en-1-one (DMAPP) and 3-(4'-diethylaminophenyl)-1-(2-pyridinyl) prop-2-en-1-one abbreviated as DEAPP have been synthesized and characterized with IR, (1)H NMR, (13)C NMR spectroscopic techniques as described previously (El-Daly et al., 2008; Gaber et al., 2009; El-Sayed, 2013). By using UV visible spectroscopy method the mole fraction ratio for copper with DMAPP and DEAPP complexes were determined and it was found to be 1:1. The stability constants of this complex have been determined by Job's method. The stability constant (Kf) of copper with DMAPP and DEAPP complexes in universal buffer pH=3.2 was determined to be 9.9×10(4) and 5.2×10(4) respectively. The effect of Cu(II) ion on the emission spectrum of the free chalcone is also assigned. Adherence to Beer's law and Ringbom optimum concentration ranges are determined. The thermal decomposition of the metal complexes is studied by TGA technique. The kinetic parameters like activation energy, pre-exponential factor and entropy of activation are estimated. The structure of complexes was energetically optimized through molecular mechanics applying MM(+) force field coupled with molecular dynamics simulation. The bond lengths and bond angles have been calculated to confirm the geometry of the ligands and their Cu(II) complexes. The mode of interaction of the chalcone to copper nanoparticles was studied. The apparent association constants of the colloidal copper nanoparticles:chalcone complexes in solution were evaluated using the spectral method and compared with the formation constant of the Cu(II) chalcone complexes. Antioxidant activity of these chalcones was evaluated by using 1,1'-diphenyl-2-picrylhydrazyl (DPPH) radicals scavenging method, which showed that the antioxidant activity of DMAPP has higher value than the DEAPP. Semi-empirical study results showed that DMAPP have higher dipole moment than DEAPP. Copyright © 2014 Elsevier B.V. All rights reserved.

Spatiotemporal control over the co-conformational switching in pH-responsive flavylium-based multistate pseudorotaxanes.

PubMed

Diniz, Ana Marta; Basílio, Nuno; Cruz, Hugo; Pina, Fernando; Parola, A Jorge

2015-01-01

A multistate molecular dyad containing flavylium and viologen units was synthesized and the pH dependent thermodynamics of the network completely characterized by a variety of spectroscopic techniques such as NMR, UV-vis and stopped-flow. The flavylium cation is only stable at acidic pH values. Above pH ≈ 5 the hydration of the flavylium leads to the formation of the hemiketal followed by ring-opening tautomerization to give the cis-chalcone. Finally, this last species isomerizes to give the trans-chalcone. For the present system only the flavylium cation and the trans-chalcone species could be detected as being thermodynamically stable. The hemiketal and the cis-chalcone are kinetic intermediates with negligible concentrations at the equilibrium. All stable species of the network were found to form 1 : 1 and 2 : 1 host : guest complexes with cucurbit[7]uril (CB7) with association constants in the ranges 10(5)-10(8) M(-1) and 10(3)-10(4) M(-1), respectively. The 1 : 1 complexes were particularly interesting to devise pH responsive bistable pseudorotaxanes: at basic pH values (≈12) the flavylium cation interconverts into the deprotonated trans-chalcone in a few minutes and under these conditions the CB7 wheel was found to be located around the viologen unit. A decrease in pH to values around 1 regenerates the flavylium cation in seconds and the macrocycle is translocated to the middle of the axle. On the other hand, if the pH is decreased to 6, the deprotonated trans-chalcone is neutralized to give a metastable species that evolves to the thermodynamically stable flavylium cation in ca. 20 hours. By taking advantage of the pH-dependent kinetics of the trans-chalcone/flavylium interconversion, spatiotemporal control of the molecular organization in pseudorotaxane systems can be achieved.

Studies on chalcone derivatives: Complex formation, thermal behavior, stability constant and antioxidant activity

NASA Astrophysics Data System (ADS)

El-Sayed, Yusif S.; Gaber, M.

2015-02-01

The chalcone 3-[4‧-dimethylaminophenyl]-1-(2-pyridyl) prop-2-en-1-one (DMAPP) and 3-(4‧-diethylaminophenyl)-1-(2-pyridinyl) prop-2-en-1-one abbreviated as DEAPP have been synthesized and characterized with IR, 1H NMR, 13C NMR spectroscopic techniques as described previously (El-Daly et al., 2008; Gaber et al., 2009; El-Sayed, 2013). By using UV visible spectroscopy method the mole fraction ratio for copper with DMAPP and DEAPP complexes were determined and it was found to be 1:1. The stability constants of this complex have been determined by Job's method. The stability constant (Kf) of copper with DMAPP and DEAPP complexes in universal buffer pH = 3.2 was determined to be 9.9 × 104 and 5.2 × 104 respectively. The effect of Cu(II) ion on the emission spectrum of the free chalcone is also assigned. Adherence to Beer's law and Ringbom optimum concentration ranges are determined. The thermal decomposition of the metal complexes is studied by TGA technique. The kinetic parameters like activation energy, pre-exponential factor and entropy of activation are estimated. The structure of complexes was energetically optimized through molecular mechanics applying MM+ force field coupled with molecular dynamics simulation. The bond lengths and bond angles have been calculated to confirm the geometry of the ligands and their Cu(II) complexes. The mode of interaction of the chalcone to copper nanoparticles was studied. The apparent association constants of the colloidal copper nanoparticles:chalcone complexes in solution were evaluated using the spectral method and compared with the formation constant of the Cu(II) chalcone complexes. Antioxidant activity of these chalcones was evaluated by using 1,1‧-diphenyl-2-picrylhydrazyl (DPPHrad) radicals scavenging method, which showed that the antioxidant activity of DMAPP has higher value than the DEAPP. Semi-empirical study results showed that DMAPP have higher dipole moment than DEAPP [1].

Viscosity and medium effects on the fluorescence and photochemical behaviour of some aryl chalcones

NASA Astrophysics Data System (ADS)

Ebeid, El-Zeiny M.; Abdel-Kader, Mahmood H.; Issa, Raafat M.; El-Daly, Samy A.

1988-05-01

The emission, excitation and absorption spectra toghether with the fluorescence and photochemical quantum yields of some chalcone derivatives have been studied in organic solvents and micellar and microemulsion media. Both 4-[2-(2-pyridyl)ethenyl] ( I) and 4-[2-(4-pyridyl)ethenyl ( II) chalcones show large positive solvatochromic effects. The fluorescence quantum yields increase substantially as the medium viscosity increases with a subsequent decrease in the photochemical quatum yield. Compounds I and II undergo excited-state molecular aggregation in concentrated solutions giving excimer-like emission that coincides with emission from crystalline samples. The enthalpies of photoassociation have been estimated. The chalcone derivative I acts as an efficient quencher of the fluorescence of the laser dye 1,4-bis (β-pyridyl-2-vinyl)benzene via a long-range mechanism. The excited-state lifetimes of both I and II are short and at 20°C their τ values are less than 800 ps.

The role of chalcones: helichrysetin, xanthohumol, and flavokawin-C in promoting neurite outgrowth in PC12 Adh cells.

PubMed

Phan, Chia-Wei; Sabaratnam, Vikineswary; Yong, Wai-Kuan; Abd Malek, Sri Nurestri

2018-05-01

Chalcones are a group of compounds widely distributed in plant kingdom. The aim of this study was to assess the neurite outgrowth stimulatory activity of selected chalcones, namely helichrysetin, xanthohumol and flavokawin-C. Using adherent rat pheochromocytoma (PC12 Adh) cells, the chalcones were subjected to neurite outgrowth assay and the extracellular nerve growth factor (NGF) levels were determined. Xanthohumol (10 μg/mL) displayed the highest (p < 0.05) percentage of neurite-bearing PC12 Adh cells and the highest (p < 0.05) NGF level in the culture medium of xanthohumol-treated cells. While, helichrysetin induced a moderately high numbers of neurite-bearing cells, flavokawin-C did not stimulate neurite outgrowth. This work supports the potential use of xanthohumol as a potential neuroactive compound to stimulate neurite outgrowth.

Ferrocenyl-cymantrenyl hetero-bimetallic chalcones: Synthesis, structure and biological properties

NASA Astrophysics Data System (ADS)

Mishra, Sasmita; Tirkey, Vijaylakshmi; Ghosh, Avishek; Dash, Hirak R.; Das, Surajit; Shukla, Madhulata; Saha, Satyen; Mobin, Sheikh M.; Chatterjee, Saurav

2015-04-01

Two new ferrocenyl-cymantrenyl bimetallic chalcones, [(CO)3Mn(η5-C5H4)C(O)CHdbnd CH(η5-C5H4)Fe(η5-C5H5)] (1) and [{(CO)3Mn(η5-C5H4)C(O)CHdbnd CH(η5-C5H4)}2Fe] (2) have been synthesized. Their reactivity study with triphenylphosphine and bis-(diphenylphosphino)ferrocene led to the isolation of phosphine substituted bimetallic chalcones (3-6). Single crystal X-ray structural characterization for 1 and its phosphine analogue (3) reveals their different conformational identity with anti-conformation for 1, while syn-conformation for 3. Investigation of antimalarial and antibacterial activities was carried out for compounds 1 and 2 against two strains of Plasmodium falciparum (3D7, K1) and four bacterial strains. TD-DFT calculation was performed for compound 1 and electrochemical properties were studied for bimetallic chalcone compounds by cyclic voltammetric technique.

Chemotherapy of leishmaniasis part-VIII: synthesis and bioevaluation of novel chalcones.

PubMed

Suryawanshi, S N; Chandra, Naveen; Kumar, Pawan; Porwal, Jyoti; Gupta, Suman

2008-11-01

Some novel dihydro-alpha-ionone based chalcones have been synthesized and evaluated for their in vitro antileishmanial activity in promastigote and amastigote model. Some of the compounds showed 100% inhibition at 5 and 2 microm/ml concentration.

Characterization of three chalcone synthase-like genes from apple (Malus x domestica Borkh.).

PubMed

Yahyaa, Mosaab; Ali, Samah; Davidovich-Rikanati, Rachel; Ibdah, Muhammad; Shachtier, Alona; Eyal, Yoram; Lewinsohn, Efraim; Ibdah, Mwafaq

2017-08-01

Apple (Malus x domestica Brokh.) is a widely cultivated deciduous tree species of significant economic importance. Apple leaves accumulate high levels of flavonoids and dihydrochalcones, and their formation is dependent on enzymes of the chalcone synthase family. Three CHS genes were cloned from apple leaves and expressed in Escherichia coli. The encoded recombinant enzymes were purified and functionally characterized. In-vitro activity assays indicated that MdCHS1, MdCHS2 and MdCHS3 code for proteins exhibiting polyketide synthase activity that accepted either p-dihydrocoumaroyl-CoA, p-coumaroyl-CoA, or cinnamoyl-CoA as starter CoA substrates in the presence of malonyl-CoA, leading to production of phloretin, naringenin chalcone, and pinocembrin chalcone. MdCHS3 coded a chalcone-dihydrochalcone synthase enzyme with narrower substrate specificity than the previous ones. The apparent Km values of MdCHS3 for p-dihydrocoumaryl-CoA and p-coumaryl-CoA were both 5.0 μM. Expression analyses of MdCHS genes varied according to tissue type. MdCHS1, MdCHS2 and MdCHS3 expression levels were associated with the levels of phloretin accumulate in the respective tissues. Copyright © 2017 Elsevier Ltd. All rights reserved.

Crystal structure and enzymatic properties of chalcone isomerase from the Antarctic vascular plant Deschampsia antarctica Desv.

PubMed

Park, Sun-Ha; Lee, Chang Woo; Cho, Sung Mi; Lee, Hyoungseok; Park, Hyun; Lee, Jungeun; Lee, Jun Hyuck

2018-01-01

Chalcone isomerase (CHI) is an important enzyme for flavonoid biosynthesis that catalyzes the intramolecular cyclization of chalcones into (S)-flavanones. CHIs have been classified into two types based on their substrate specificity. Type I CHIs use naringenin chalcone as a substrate and are found in most of plants besides legumes, whereas type II CHIs in leguminous plants can also utilize isoliquiritigenin. In this study, we found that the CHI from the Antarctic plant Deschampsia antarctica (DaCHI1) is of type I based on sequence homology but can use type II CHI substrates. To clarify the enzymatic mechanism of DaCHI1 at the molecular level, the crystal structures of unliganded DaCHI1 and isoliquiritigenin-bound DaCHI1 were determined at 2.7 and 2.1 Å resolutions, respectively. The structures revealed that isoliquiritigenin binds to the active site of DaCHI1 and induces conformational changes. Additionally, the activity assay showed that while DaCHI1 exhibits substrate preference for naringenin chalcone, it can also utilize isoliquiritigenin although the catalytic activity was relatively low. Based on these results, we propose that DaCHI1 uses various substrates to produce antioxidant flavonoids as an adaptation to oxidative stresses associated with harsh environmental conditions.

QSAR-driven design, synthesis and discovery of potent chalcone derivatives with antitubercular activity.

PubMed

Gomes, Marcelo N; Braga, Rodolpho C; Grzelak, Edyta M; Neves, Bruno J; Muratov, Eugene; Ma, Rui; Klein, Larry L; Cho, Sanghyun; Oliveira, Guilherme R; Franzblau, Scott G; Andrade, Carolina Horta

2017-09-08

New anti-tuberculosis (anti-TB) drugs are urgently needed to battle drug-resistant Mycobacterium tuberculosis strains and to shorten the current 6-12-month treatment regimen. In this work, we have continued the efforts to develop chalcone-based anti-TB compounds by using an in silico design and QSAR-driven approach. Initially, we developed SAR rules and binary QSAR models using literature data for targeted design of new heteroaryl chalcone compounds with anti-TB activity. Using these models, we prioritized 33 compounds for synthesis and biological evaluation. As a result, 10 heteroaryl chalcone compounds (4, 8, 9, 11, 13, 17-20, and 23) were found to exhibit nanomolar activity against replicating mycobacteria, low micromolar activity against nonreplicating bacteria, and nanomolar and micromolar against rifampin (RMP) and isoniazid (INH) monoresistant strains (rRMP and rINH) (<1 μM and <10 μM, respectively). The series also show low activity against commensal bacteria and generally show good selectivity toward M. tuberculosis, with very low cytotoxicity against Vero cells (SI = 11-545). Our results suggest that our designed heteroaryl chalcone compounds, due to their high potency and selectivity, are promising anti-TB agents. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Crystal structure and enzymatic properties of chalcone isomerase from the Antarctic vascular plant Deschampsia antarctica Desv.

PubMed Central

Lee, Hyoungseok; Park, Hyun; Lee, Jungeun

2018-01-01

Chalcone isomerase (CHI) is an important enzyme for flavonoid biosynthesis that catalyzes the intramolecular cyclization of chalcones into (S)-flavanones. CHIs have been classified into two types based on their substrate specificity. Type I CHIs use naringenin chalcone as a substrate and are found in most of plants besides legumes, whereas type II CHIs in leguminous plants can also utilize isoliquiritigenin. In this study, we found that the CHI from the Antarctic plant Deschampsia antarctica (DaCHI1) is of type I based on sequence homology but can use type II CHI substrates. To clarify the enzymatic mechanism of DaCHI1 at the molecular level, the crystal structures of unliganded DaCHI1 and isoliquiritigenin-bound DaCHI1 were determined at 2.7 and 2.1 Å resolutions, respectively. The structures revealed that isoliquiritigenin binds to the active site of DaCHI1 and induces conformational changes. Additionally, the activity assay showed that while DaCHI1 exhibits substrate preference for naringenin chalcone, it can also utilize isoliquiritigenin although the catalytic activity was relatively low. Based on these results, we propose that DaCHI1 uses various substrates to produce antioxidant flavonoids as an adaptation to oxidative stresses associated with harsh environmental conditions. PMID:29394293

DOE Office of Scientific and Technical Information (OSTI.GOV)

D'silva, E.D., E-mail: deepak.dsilva@gmail.com; Podagatlapalli, G. Krishna; Venugopal Rao, S., E-mail: soma_venu@yahoo.com

Graphical abstract: Photograph and schematic representation of Z-scan experimental setup used to investigate third order nonlinear properties of the chalcone materials. Highlights: ► Br and NO{sub 2} substituted chalcone derivatives were exposed to picosecond laser pulses. ► Third-order nonlinear optical (NLO) properties were investigated. ► Compounds show promising third-order and optical limiting properties. ► These materials found suitable for electrical and optical applications. -- Abstract: In this paper we present results from the experimental study of third-order nonlinear optical (NLO) properties of three molecules of Br and NO{sub 2} substituted chalcone derivatives namely (2E)-1-(4-bromophenyl)-3-[4(methylsulfanyl)phenyl]prop-2-en-1-one (4Br4MSP), (2E)-1-(3-bromophenyl)-3-[4-(methylsulfanyl) phenyl]prop-2-en-1-one (3Br4MSP) and (2E)-3[4(methylsulfanyl)more » phenyl]-1-(4-nitrophenyl)prop-2-en-1-one (4N4MSP). The NLO properties have been investigated by Z-scan technique using 2 ps laser pulses at 800 nm. The nonlinear refractive indices, nonlinear absorption coefficient, and the magnitude of third-order susceptibility have been determined. The values obtained are of the order of 10{sup −7} cm{sup 2}/GW, 10{sup −3} cm/GW and 10{sup −14} esu respectively. The molecular second hyperpolarizability for the chalcone derivatives is of the order of 10{sup −32} esu. The coupling factor, excited state cross section, ground state cross section etc. were determined. The optical limiting (OL) property was studied. The results suggest that the nonlinear properties investigated for present chalcones are comparable with some of the reported chalcone derivatives and can be desirable for NLO applications.« less

Synthesis and anti-inflammatory effect of chalcones and related compounds.

PubMed

Hsieh, H K; Lee, T H; Wang, J P; Wang, J J; Lin, C N

1998-01-01

Mast cell and neutrophil degranulations are the important players in inflammatory disorders. Combined with potent inhibition of chemical mediators released from mast cells and neutrophil degranulations, it could be a promising anti-inflammatory agent. 2',5'-Dihydroxychalcone has been reported as a potent chemical mediator and cyclooxygenase inhibitor. In an effort to continually develop potent anti-inflammatory agents, a novel series of chalcone, 2'- and 3'-hydroxychalcones, 2',5'-dihydroxychalcones and flavanones were continually synthesized to evaluate their inhibitory effects on the activation of mast cells and neutrophils and the inhibitory effect on phlogist-induced hind-paw edema in mice. A series of chalcones and related compounds were prepared by Claisen-Schmidt condensation of appropriate acetophenones with appropriate aromatic aldehyde and the anti-inflammatory activities of these synthetic compounds were studied on inhibitory effects on the activation of mast cells and neutrophils. Some chalcones showed strong inhibitory effects on the release of beta-glucuronidase and histamine from rat peritoneal mast cells stimulated with compound 48/80. Almost all chalcones and 4'-hydroxyflavanone exhibited potent inhibitory effects on the release of beta-glucuronidase and lysozyme from rat neutrophils stimulated with formyl-Met-Leu-Phe (fMLP). Some chalcones showed potent inhibitory effects on superoxide formation of rat neutrophils stimulated with fMLP/cytochalasin B (CB) or phorbol myristate acetate (PMA). 2',3-Dihydroxy-, 2',5'-dihydroxy-4-chloro-, and 2',5'-dihydroxychalcone showed remarkable inhibitory effects on hind-paw edema induced by polymyxin B in normal as well as in adrenalectomized mice. These results indicated that the anti-inflammatory effects of these compounds were mediated, at least partly, through the suppression of chemical mediators released from mast cells and neutrophils.

Therapeutic potential of chalcones as cardiovascular agents.

PubMed

Mahapatra, Debarshi Kar; Bharti, Sanjay Kumar

2016-03-01

Cardiovascular diseases are the leading cause of death affecting 17.3 million people across the globe and are estimated to affect 23.3 million people by year 2030. In recent years, about 7.3 million people died due to coronary heart disease, 9.4 million deaths due to high blood pressure and 6.2 million due to stroke, where obesity and atherosclerotic progression remain the chief pathological factors. The search for newer and better cardiovascular agents is the foremost need to manage cardiac patient population across the world. Several natural and (semi) synthetic chalcones deserve the credit of being potential candidates to inhibit various cardiovascular, hematological and anti-obesity targets like angiotensin converting enzyme (ACE), cholesteryl ester transfer protein (CETP), diacylglycerol acyltransferase (DGAT), acyl-coenzyme A: cholesterol acyltransferase (ACAT), pancreatic lipase (PL), lipoprotein lipase (LPL), calcium (Ca(2+))/potassium (K(+)) channel, COX-1, TXA2 and TXB2. In this review, a comprehensive study of chalcones, their therapeutic targets, structure activity relationships (SARs), mechanisms of actions (MOAs) have been discussed. Chemically diverse chalcone scaffolds, their derivatives including structural manipulation of both aryl rings, replacement with heteroaryl scaffold(s) and hybridization through conjugation with other pharmacologically active scaffold have been highlighted. Chalcones which showed promising activity and have a well-defined MOAs, SARs must be considered as prototype for the design and development of potential anti-hypertensive, anti-anginal, anti-arrhythmic and cardioprotective agents. With the knowledge of these molecular targets, structural insights and SARs, this review may be helpful for (medicinal) chemists to design more potent, safe, selective and cost effective chalcone derivatives as potential cardiovascular agents. Copyright © 2016 Elsevier Inc. All rights reserved.

Chemopreventive effect of chalcone derivative, L2H17, in colon cancer development.

PubMed

Xu, Shanmei; Chen, Minxiao; Chen, Wenbo; Hui, Junguo; Ji, Jiansong; Hu, Shuping; Zhou, Jianmin; Wang, Yi; Liang, Guang

2015-11-09

Colon cancer is the third most commonly diagnosed cancer and the second leading cause of cancer mortality worldwide. Chalcone and its derivatives are reported to exhibit anti-cancer effects in several cancer cell lines, including colon cancer cells. In addition, chalcones have advantages such as poor interaction with DNA and low risk of mutagenesity. In our previous study, a group of chalcone derivatives were synthesized and exhibited strong anti-inflammatory activities. In this study, we evaluated the anti-cancer effects of the chalcone derivative, L2H17, in colon cancer cells. The cytotoxicities of L2H17 on various colon cancer cell lines were investigated by MTT and clonogenic assay. Cell cycle and apoptosis analysis were performed to evaluate the molecular mechanism of L2H17-mediated inhibition of tumor growth. Also, scratch wound and matrigel invasion experiments were performed to estimate the cell migration and invasion after L2H17 treatment. Finally, we observed the anti-colon cancer effects of L2H17 in vivo. Our data show that compound L2H17 exhibited selective cytotoxic effect on colon cancer cells, via inducing G0/G1 cell cycle arrest and apoptosis in CT26.WT cells. Furthermore, L2H17 treatment decreased cell migration and invasion of CT26.WT cells. In addition, L2H17 possessed marked anti-tumor activity in vivo. The molecular mechanism of L2H17-mediated inhibition of tumor promotion and progression were function through inactivated NF-κB and Akt signaling pathways. All these findings show that L2H17 might be a potential growth inhibitory chalcones derivative for colon cancer cells.

Antifungal activity of 6-quinolinyl N-oxide chalcones against Paracoccidioides.

PubMed

de Sá, Nívea Pereira; Cisalpino, Patrícia Silva; Tavares, Luciana de Carvalho; Espíndola, Leandro; Pizzolatti, Moacir Geraldo; Santos, Patrícia Campi; de Paula, Talles Prosperi; Rosa, Carlos Augusto; de Souza, Daniele da Glória; Santos, Daniel Assis; Johann, Susana

2015-03-01

Chalcones are an important class of natural compounds that have been widely applied as synthons in synthetic organic chemistry and possess diverse and interesting biological properties. We conducted tests with the synthetic substances 6-quinolinyl N-oxide chalcones 4c and 4e to determine their antifungal activity against several isolates of Paracoccidioides spp. and their activity in a murine model. We also determined whether the chalcones interacted with other drugs or interfered with the morphology of Paracoccidioides brasiliensis (Pb18) yeast cells. We verified that the substances were active against Paracoccidioides spp., but we did not show an interaction with the drugs tested when only the fractional inhibitory concentration index values were considered individually. We observed that the substances induced in vitro morphological changes. Compounds 4c and 4e showed activity similar to itraconazole in treated mice, as demonstrated by their ability to reduce the number of cfu recovered from the lungs. Histopathological analysis showed that animals treated with 4c presented fewer areas containing inflammatory infiltrate and larger areas of preserved lung tissue, whereas animals treated with itraconazole showed accumulation of inflammatory infiltrate and some granulomas. Mice treated with 4e exhibited inflammation that compromised the tissue. The results presented in this paper confirm the antifungal potential of the chalcones tested. The chalcone 4c was the more effective at controlling the disease in mice and this compound could be a candidate for future studies of the treatment of paracoccidioidomycosis. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Plant polyketide synthases: a chalcone synthase-type enzyme which performs a condensation reaction with methylmalonyl-CoA in the biosynthesis of C-methylated chalcones.

PubMed

Schröder, J; Raiber, S; Berger, T; Schmidt, A; Schmidt, J; Soares-Sello, A M; Bardshiri, E; Strack, D; Simpson, T J; Veit, M; Schröder, G

1998-06-09

Heterologous screening of a cDNA library from Pinusstrobus seedlings identified clones for two chalcone synthase (CHS) related proteins (PStrCHS1 and PStrCHS2, 87.6% identity). Heterologous expression in Escherichia coli showed that PStrCHS1 performed the typical CHS reaction, that it used starter CoA-esters from the phenylpropanoid pathway, and that it performed three condensation reactions with malonyl-CoA, followed by the ring closure to the chalcone. PstrCHS2 was completely inactive with these starters and also with linear CoA-esters. Activity was detected only with a diketide derivative (N-acetylcysteamine thioester of 3-oxo-5-phenylpent-4-enoic acid) that corresponded to the CHS reaction intermediate postulated after the first condensation reaction. PstrCHS2 performed only one condensation, with 6-styryl-4-hydroxy-2-pyrone derivatives as release products. The enzyme preferred methylmalonyl-CoA against malonyl-CoA, if only methylmalonyl-CoA was available. These properties and a comparison with the CHS from Pinus sylvestris suggested for PstrCHS2 a special function in the biosynthesis of secondary products. In contrast to P. sylvestris, P. strobus contains C-methylated chalcone derivatives, and the methyl group is at the position predicted from a chain extension with methylmalonyl-CoA in the second condensation of the biosynthetic reaction sequence. We propose that PstrCHS2 specifically contributes the condensing reaction with methylmalonyl-CoA to yield a methylated triketide intermediate. We discuss a model that the biosynthesis of C-methylated chalcones represents the simplest example of a modular polyketide synthase.

Design, synthesis, and biological evaluation of prenylated chalcones as 5-LOX inhibitors.

PubMed

Reddy, Nimmanapalli P; Aparoy, Polamarasetty; Reddy, T Chandra Mohan; Achari, Chandrani; Sridhar, P Ramu; Reddanna, Pallu

2010-08-15

Ten novel mono- and di-O-prenylated chalcone derivatives were designed on the basis of a homology derived molecular model of 5-lipoxygenase (5-LOX). The compounds were docked into 5-LOX active site and the binding characteristics were quantified using LUDI. To verify our theoretical assumption, the molecules were synthesized and tested for their 5-LOX inhibitory activities. The synthesis was carried out by Claisen-Schmidt condensation reaction of mono- and di-O-prenylated acetophenones with appropriate aldehydes. 5-LOX in vitro inhibition assay showed higher potency of di-O-prenylated chalcones than their mono-O-prenylated chalcone analogs. Compound 5e exhibited good inhibition with an IC(50) at 4 microM. The overall trend for the binding energies calculated and LUDI score was in good qualitative agreement with the experimental data. Further, the compound 5e showed potent anti-proliferative effects (GI(50) at 9 microM) on breast cancer cell line, MCF-7. Copyright 2010 Elsevier Ltd. All rights reserved.

Studies of structure-activity relationship on plant polyphenol-induced suppression of human liver cancer cells.

PubMed

Loa, Jacky; Chow, Pierce; Zhang, Kai

2009-05-01

To study anticancer activities of 68 plant polyphenols with different backbone structures and various substitutions and to analyze the structure-activity relationships. Antiproliferative activity of 68 plant polyphenols on human liver cancer cells were screened by the 3-[4,5-dimethylthiazol-2yl]-2,5-diphenyltetrazolium bromide method. Structure-activity relationships were analyzed by comparison of their activities with selected structures. Cell cycle progression was assayed by flow cytometry analysis and apoptosis was analyzed by DNA fragment assay. Based on their backbone structures, 68 polyphenols were sub-classed to flavonoids (chalcones, flavanones, flavones and isoflavones), chromones and coumarins. The order of their potency to suppress the human liver cancer cells is chalcones > flavones > chromones > isoflavones > flavanones > coumarins. Chalcones comprise the most potent group with IC(50) values ranging from 21.69 to 197 microM. Top nine most potent chalcones in the group have hydroxylation at 2'-carbon position in B-ring. Flavones ranked second in their potencies. Quercetin, 4-hydroxyflavone and luteolin are three hydroxyflavones with highest potencies in this group. Their IC(50) values are 30.81, 39.29 and 71.17 microM, respectively. Chromones, isoflavones, flavanones and coumarins showed much lower potencies when compared to the first two groups with IC(50) ranges of 61 to >400, 131 to >400, 138 to >400 and 360.85 to >400 microM, respectively. In mechanistic studies, the most potent chalcone, 2,2'-dihydroxychalcone could induce G2/M arrest and then apoptosis of the cancer cells. An analysis of structure-activity relationship showed that following structures are required for their inhibitory potencies on human liver cancer cells: (1) of the six sub-classes of the polyphenols tested, the unique backbone structure of chalcones with a open C-ring; (2) within the chalcone group, hydroxyl substitution at 2'-carbon of B-ring; (3) hydroxyl substitution at 3'-carbon in B-ring of flavones. However, some other structures were found to decrease their potencies: e.g. substitutions by sugar moieties in flavones. These data are valuable for design and modification of new polyphenols, which could be potential antiproliferative agents of cancer cells.

Synthesis and structure elucidation of a series of pyranochromene chalcones and flavanones using 1D and 2D NMR spectroscopy and X-ray crystallography.

PubMed

Pawar, Sunayna S; Koorbanally, Neil A

2014-06-01

A series of novel pyranochromene chalcones and corresponding flavanones were synthesized. This is the first report on the confirmation of the absolute configuration of chromene-based flavanones using X-ray crystallography. These compounds were characterized by 2D NMR spectroscopy, and their assignments are reported herein. The 3D structure of the chalcone 3b and flavanone 4g was determined by X-ray crystallography, and the structure of the flavanone was confirmed to be in the S configuration at C-2. Copyright © 2014 John Wiley & Sons, Ltd.

Replacement of the double bond of antitubulin chalcones with triazoles and tetrazoles: Synthesis and biological evaluation.

PubMed

Mesenzani, Ornella; Massarotti, Alberto; Giustiniano, Mariateresa; Pirali, Tracey; Bevilacqua, Valentina; Caldarelli, Antonio; Canonico, Pierluigi; Sorba, Giovanni; Novellino, Ettore; Genazzani, Armando A; Tron, Gian Cesare

2011-01-15

In the chalcone scaffold, it is thought that the double bond is an important structural linker but it is likely not essential for the interaction with tubulin. Yet, it may be a potential site of metabolic degradation and interaction with biological nucleophiles. In this letter, we have replaced this olefinic portion of chalcones with two metabolically stable and chemically inert heterocyclic rings, namely triazole or tetrazole. Yet, our biologic data suggest that, unlike in other antitubulinic structures, the olephinic ring might not be merely a structural linker. Copyright © 2010 Elsevier Ltd. All rights reserved.

Synthesis and biological activities of fluorinated chalcone derivatives.

PubMed

Nakamura, Chika; Kawasaki, Nobuhide; Miyataka, Hideki; Jayachandran, Ezhuthachan; Kim, In Ho; Kirk, Kenneth L; Taguchi, Takeo; Takeuchi, Yoshio; Hori, Hitoshi; Satoh, Toshio

2002-03-01

We have designed and synthesized new 5-lipoxygenase inhibitors, fluorinated 3,4-dihydroxychalcones, and evaluated their biological activities with respect to antiperoxidation activity and in vitro antitumor activities. All fluorinated chalcones tested showed 5-lipoxygenase inhibition on rat basophilic leukemia-1 (RBL-1) cells and inhibitory action on Fe(3+)-ADP induced NADPH-dependent lipid peroxidation in rat liver microsomes. The potencies were comparable or better to that of the lead 3,4-dihydroxychalcone. 6-Fluoro-3,4-dihydroxy-2',4'-dimethoxy chalcone (7) was the most effective compound in the in vitro assay using a human cancer cell line panel (HCC panel) consisting of 39 systems.

Employing NMR Spectroscopy To Evaluate Transmission of Electronic Effects in 4-Substituted Chalcones

NASA Astrophysics Data System (ADS)

Wachter-Jurcsak, Nanette; Zamani, Hossein

1999-05-01

Described is an organic synthesis experiment that demonstrates the electronic transmission by substituents. The effect of substitution at the para-position of the styryl ring of 1,3-diphenyl-2-propenones (chalcones) by typical electron-donating or -accepting groups can be observed by proton and carbon-13 NMR spectroscopy. A linear correlation is observed when the differences in chemical shift measurements for H are plotted against the corresponding Hammett substituent constant values. Good correlation between carbon-13 chemical shifts of the alpha carbon are also observed. The syntheses of the 4-substituted chalcones is presented as well as a brief discussion of the theory.

Chemistry of isoflavone heteroanalogs. 11. Benzodioxane analogs of chalcone, flavone, and isoflavone

DOE Office of Scientific and Technical Information (OSTI.GOV)

Khilya, V.P.; Aitmambetov, A.; Turov, A.V.

1986-08-01

Benzodioxane analogs of chalcones and their epoxides have been prepared. Different types of analogs of natural flavonolignan - silibin - have been synthesized from these compounds. The PMR spectra of the new compounds and the results of the preliminary biological testings are reported and discussed.

Role of nuclear factor-κB and heme oxygenase-1 in the mechanism of action of an anti-inflammatory chalcone derivative in RAW 264.7 cells

PubMed Central

Alcaraz, María José; Vicente, Ana María; Araico, Amparo; Dominguez, José N; Terencio, María Carmen; Ferrándiz, María Luisa

2004-01-01

The synthetic chalcone 3′,4′,5′,3,4,5-hexamethoxy-chalcone (CH) is an anti-inflammatory compound able to reduce nitric oxide (NO) production by inhibition of inducible NO synthase protein synthesis. In this work, we have studied the mechanisms of action of this compound. CH (10–30 μM) prevents the overproduction of NO in RAW 264.7 macrophages stimulated with lipopolysaccharide (1 μg ml−1) due to the inhibition of nuclear factor κB (NF-κB) activation. We have shown that treatment of cells with CH results in diminished degradation of the NF-κB–IκB complex leading to inhibition of NF-κB translocation into the nucleus, DNA binding and transcriptional activity. We also demonstrate the ability of this compound to activate NfE2-related factor (Nrf2) and induce heme oxygenase-1 (HO-1). Our results indicate that CH determines a rapid but nontoxic increase of intracellular oxidative species, which could be responsible for Nrf2 activation and HO-1 induction by this chalcone derivative.  This novel anti-inflammatory agent simultaneously induces a cytoprotective response (HO-1) and downregulates an inflammatory pathway (NF-κB) with a mechanism of action different from antioxidant chalcones. PMID:15249426

Design and synthesis of novel chalcones as potent selective monoamine oxidase-B inhibitors.

PubMed

Hammuda, Arwa; Shalaby, Raed; Rovida, Stefano; Edmondson, Dale E; Binda, Claudia; Khalil, Ashraf

2016-05-23

A novel series of substituted chalcones were designed and synthesized to be evaluated as selective human MAO-B inhibitors. A combination of either methylsulfonyl or trifluoromethyl substituents on the aromatic ketone moiety with a benzodioxol ring on the other end of the chalcone scaffold was investigated. The compounds were tested for their inhibitory activities on both human MAO-A and B. All compounds appeared to be selective MAO-B inhibitors with Ki values in the micromolar to submicromolar range. Molecular modeling studies have been performed to get insight into the binding mode of the synthesized compounds to human MAO-B active site. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

HIGHLY DISATEREOSELECTIVE MICHAEL ADDITION OF FLAVANONE TO ITS CHALCONE PRECURSOR UNDER SOLVENT-FREE CONDITIONS USING MICROWAVES [POSTER

EPA Science Inventory

Substituted 2'-hydroxychalcones were found to give an equilibrium mixture of the starting chalcone and the corresponding flavanone inf 4.6-1:3 ratio in the presence of DBU gave two hitherto unknown diasteromeric dimers in a highly diastereoselective Michael addition of the carban...

HIGHLY DIASTEREOSELECTIVE MICHAEL ADDITION OF FLAVANONE TO ITS CHALCONE PRECURSOR UNDER SOLVENT-FREE CONDITIONS USING MICROWAVES

EPA Science Inventory

Substituted 2'-hydroxychalcones were found to give an equilibrium mixture of the starting chalcone and the corresponding flavanone in 4:6 - 1:3 ratio in the presence of various supports and MW irradiation. MW irradiation of 2'-hydroxychalcones in the presence of DBU gave two hit...

Cloning and Functional Analysis of Three Chalcone Synthases from the Flowers of Safflowers Carthamus tinctorius.

PubMed

Shinozaki, Junichi; Kenmoku, Hiromichi; Nihei, Kenichi; Masuda, Kazuo; Noji, Masaaki; Konno, Katsuhiro; Asakawa, Yoshinori; Kazuma, Kohei

2016-06-01

The flowers of safflowers (Carthamus tinctorius L.) are very important as they are the sole source of their distinct pigments, i.e. carthamus-red and -yellows, and have historically had strong connections to the cultural side of human activities such as natural dyes, rouge, and traditional medicines. The distinct pigments are quinochalcone C-glucosides, which are found specifically in the flowers of C. tinctorius. To investigate the biosynthetic pathways of quinochalcone C-glucosides, de novo assembly of the transcriptome was performed on the flowers using an Illumina sequencing platform to obtain 69,312 annotated coding DNA sequences. Three chalcone synthase like genes, CtCHS1, 2 and 3 were focused on and cloned, which might be involved in quinochalcone C-glucosides biosynthesis by establishing the C6-C3-C6 chalcone skeleton. It was demonstrated that all the recombinant CtCHSs could recognize p-coumaroyl-CoA, caffeoyl-CoA, feruloyl-CoA, and sinapoyl-CoA as starter substrates. This is the first report on the cloning and functional analysis of the three chalcone synthase genes from the flowers of C. tinctorius.

Qualitative and Quantitative Analysis of Flower Pigments in Chocolate Cosmos, Cosmos atrosanguineus, and its Hybrids.

PubMed

Amamiya, Kotarou; Iwashina, Tsukasa

2016-01-01

Two major anthocyanins, cyanidin 3-O-glucoside and 3-O-rutinoside, were isolated from the black flowers of Cosmos atrosanguineus cultivar 'Choco Mocha', together with three minor anthocyanins, cyanidin 3-O-malonylglucoside, pelargonidin 3-O-glucoside and 3-O-rutinoside. A chalcone, butein 4'-O-glucoside and three minor flavanones were isolated from the red flowers of C. atrosanguineis x C. sulphureus cultivar 'Rouge Rouge'. The anthocyanins and chalcone accumulation of cultivar 'Choco Mocha' and its hybrid cultivars 'Brown Rouge', 'Forte Rouge', 'Rouge Rouge' and 'Noel Rouge' was surveyed by quantitative HPLC. Total anthocyanins of black flower cultivars 'Choco Mocha' and 'Brown Rouge' were 3-4-folds higher than that of the red flower cultivar 'Noel Rouge'. On the other hand, total chalcone of 'Noel Rouge' was 10-77-folds higher compared with those of other cultivars, 'Brown Rouge', 'Forte Rouge' and 'Rouge Rouge'. It was shown that the flower color variations from red to black of Chocolate Cosmos and its hybrids are due to the difference in the relative amounts of anthocyanins and chalcone.

Toxicological assessment of Ashitaba Chalcone.

PubMed

Maronpot, Robert R

2015-03-01

The plant Angelica keiskei contains two main physiologically active flavonoid chalcones, 4-hydroxyderricin and xanthoangelol. Known as ashitaba in Japan, powder from the sap is widely consumed for its medicinal properties in Asia as a dietary supplement. Limited previously reported mammalian studies were without evidence of toxicity. GLP studies reported here, including a bacterial reverse mutation assay, a chromosome aberration assay, and an in vivo micronucleus assay are negative for genotoxicity. A GLP- compliant 90-day repeated oral gavage study of ashitaba yellow sap powder containing 8.45% chalcones in Sprague Dawley rats resulted in expected known physiological effects on coagulation parameters and plasma lipids at 300 and 1000 mg/kg/day. Ashitaba-related pathology included a dose-related male rat-specific alpha 2-urinary globulin nephropathy at 100, 300, and 1000 mg/kg/day and jejunal lymphangiectasia in both sexes at 1000 mg/kg/day. All other study parameters and histopathological changes were incidental or not of toxicological concern. Based on these studies ashitaba chalcone powder is not genotoxic with a NOAEL of 300 mg/kg in male and female rats. Copyright © 2014 Elsevier Ltd. All rights reserved.

Synthesis and anti-parasitic activity of a novel quinolinone-chalcone series.

PubMed

Roussaki, Marina; Hall, Belinda; Lima, Sofia Costa; da Silva, Anabela Cordeiro; Wilkinson, Shane; Detsi, Anastasia

2013-12-01

A series of novel quinolinone-chalcone hybrids and analogues were designed, synthesized and their biological activity against the mammalian stages of Trypanosoma brucei and Leishmania infantum evaluated. Promising molecular scaffolds with significant microbicidal activity and low cytotoxicity were identified. Quinolinone-chalcone 10 exhibited anti-parasitic properties against both organisms, being the most potent anti-L. infantum agent of the entire series (IC50 value of 1.3±0.1 μM). Compounds 4 and 11 showed potency toward the intracellular, amastigote stage of L. infantum (IC50 values of 2.1±0.6 and 3.1±1.05 μM, respectively). Promising trypanocidal compounds include 5 and 10 (IC50 values of 2.6±0.1 and 3.3±0.1 μM, respectively) as well as 6 and 9 (both having IC50 values of <5 μM). Chemical modifications on the quinolinone-chalcone scaffold were performed on selected compounds in order to investigate the influence of these structural features on antiparasitic activity. Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemoprotective potentials of homoisoflavonoids and chalcones of Dracaena cinnabari: modulations of drug-metabolizing enzymes and antioxidant activity.

PubMed

Machala, M; Kubínová, R; Horavová, P; Suchý, V

2001-03-01

A series of homoisoflavonoids and chalcones, isolated from the endemic tropical plant Dracaena cinnabari Balf. (Agavaceae), were tested for their potential to inhibit cytochrome P4501A (CYP1A) enzymes and Fe-enhanced in vitro peroxidation of microsomal lipids in C57B1/6 mouse liver. The effects of the polyphenolic compounds were compared with those of prototypal flavonoid modulators of CYP1A and the well-known antioxidant, butylated hydroxytoluene. 2-Hydroxychalcone and partly 4,6-dihydroxychalcone were found to be strong inhibitors of CYP1A-dependent 7-ethoxyresorufin O-deethylase (EROD) activity in vitro comparable to the effects of quercetin and chrysin. The first screening of flavonoids and chalcones of Dracaena cinnabari for antioxidant activity was done in an in vitro microsomal peroxidation assay. While chalcones were shown to be poor antioxidants, 7,8-methylenedioxy-3(4-hydroxybenzyl) chromane, as one of the tested homoisoflavonoids, exhibited a strong antioxidant activity comparable to that of the strongest flavonol antioxidant, quercetin. Copyright 2001 John Wiley & Sons, Ltd.

Positive selection sites in tertiary structure of Leguminosae chalcone isomerase 1.

PubMed

Wang, R K; Zhan, S F; Zhao, T J; Zhou, X L; Wang, C E

2015-03-20

Isoflavonoids and the related synthesis enzyme, chalcone isomerase 1 (CHI1), are unique in the Leguminosae, with diverse biological functions. Among the Leguminosae, the soybean is an important oil, protein crop, and model plant. In this study, we aimed to detect the generation pattern of Leguminosae CHI1. Genome-wide sequence analysis of CHI in 3 Leguminosae and 3 other closely related model plants was performed; the expression levels of soybean chalcone isomerases were also analyzed. By comparing positively selected sites and their protein structures, we retrieved the evolution patterns for Leguminosae CHI1. A total of 28 CHI and 7 FAP3 (CHI4) genes were identified and separated into 4 clades: CHI1, CHI2, CHI3, and FAP3. Soybean genes belonging to the same chalcone isomerase subfamily had similar expression patterns. CHI1, the unique chalcone isomerase subfamily in Leguminosae, showed signs of significant positive selection as well as special expression characteristics, indicating an accelerated evolution throughout its divergence. Eight sites were identified as undergoing positive selection with high confidence. When mapped onto the tertiary structure of CHI1, these 8 sites were observed surrounding the enzyme substrate only; some of them connected to the catalytic core of CHI. Thus, we inferred that the generation of Leguminosae CHI1 is dependent on the positively selected amino acids surrounding its catalytic substrate. In other words, the evolution of CHI1 was driven by specific selection or processing conditions within the substrate.

Green Synthesis, Spectrofluorometric Characterization and Antibacterial Activity of Heterocyclic Compound from Chalcone on the Basis of in Vitro and Quantum Chemistry Calculation.

PubMed

Khan, Salman A

2017-05-01

2-amino-4-(4-bromophenyl)-8-methoxy-5,6-dihydrobenzo[h]quinoline-3-carbonitrile (ABDC) was synthesized by the reaction of (2E)-2-(4 bromobenzylidene) - 6 -methoxy-3,4-dihydronaphthalen-1(2H)-one (Chalcone) with malononitrile and ammonium acetate under microwave irradiation. Chalcone was synthesised by the reaction 4-bromobenzaldehyd, 6-methoxy-1,2,3,4-tetrahydro-naphthalin-1-one under the same condition. Structure of ABDC was conformed by 1 H and 13 C NMR, FT-IR, EI-MS spectral studies and elemental analysis. The electronic absorption and fluorescence spectra of ABDC have been studied in solvents of different polarities, and the data were used to study the solvatochromic properties such as excitation coefficient, stokes shift, oscillator strength, transition dipole moment and fluorescence quantum yield. The absorption maximum and fluorescence emission maximum was observed red shift when increase solvent polarity n-Hexane to DMSO. ABDC undergoes solubilization in different micelles and may be used as a probe and quencher to determine the critical micelle concentration (CMC) of CTAB and SDS. The anti-bacterial activity of chalcone and its cyclized product ABDC was tested in vitro by the disk diffusion assay against two Gram-positive and two Gram-negative bacteria was determined with the reference of standard drug Tetracycline. Results showed that the ABDC is better anti-bacterial agent as compared to chalcone. The anti-bacterial activity was further supported by the quantum chemistry calculation.

Newly-synthesized chalcones-inhibition of adherence and biofilm formation of methicillin-resistant Staphylococcus aureus

PubMed Central

Bozic, Dragana D.; Milenkovic, Marina; Ivkovic, Branka; Cirkovic, Ivana

2014-01-01

Biofilm formation and adherence of bacteria to host tissue are one of the most important virulence factors of methicillin-resistant strains of Staphylococcus aureus (MRSA). The number of resistant strains is seriously increasing during the past years and bacteria have become resistant, not only to methicillin, but also to other commonly used antistaphylococcal antibiotics. There is a great need for discovering a novel antimicrobial agent for the treatment of staphylococcal infections. One of the most promising groups of compounds appears to be chalcones. In present study we evaluated the in vitro effect of three newly synthesized chalcones: 1,3- Bis-(2-hydroxy-phenyl)-propenone, 3-(3-Hydroxy-phenyl)-1-(2-hydroxy-phenyl)-propenone and 3-(4-Hydroxy-phenyl)-1-(2-hydroxy-phenyl)-propenone on glycocalyx production, biofilm formation and adherence to human fibronectin of clinical isolates and laboratory control strain of MRSA (ATCC 43300). Subinhibitory concentrations of the tested compounds reduced the production of glycocalyx, biofilm formation and adherence to human fibronectin of all MRSA strains. Inhibition of biofilm formation was dose dependent and the most effective was 1,3- Bis-(2-hydroxy-phenyl)-propenone. In our study we demonstrated that three newly-synthesized chalcones exhibited significant effect on adherence and biofilm formation of MRSA strains. Chalcones may be considered as promising new antimicrobial agents that can be used for prevention of staphylococcal infections or as adjunct to antibiotics in conventional therapy. PMID:24948943

Synthesis and characterization of a symmetric bis(7-hydroxyflavylium) containing a methyl viologen bridge.

PubMed

Diniz, Ana M; Pinheiro, Carlos; Petrov, Vesselin; Parola, A Jorge; Pina, Fernando

2011-05-27

A symmetric bis(flavylium) constituted by two 7-hydroxyflavylium moieties linked by a methylviologen bridge was synthesized. The thermodynamic and kinetics of the network of chemical reactions involving bis(flavylium) and the model compound 7-hydroxy-4'-methylflavylium was completely characterized by means of direct and reverse pH jumps (stopped flow) and flash photolysis. Both compounds follow the usual pH-dependent network of chemical reactions of flavylium derivatives. The equilibrium species of the model compound are the flavylium cation (acidic species) and the trans-chalcone (basic species) with an apparent pK'(a)=2.85. In the case of the bis(flavylium) it was possible to characterize by (1)H NMR spectroscopy three species with different degrees of isomerization: all flavylium, flavylium-trans-chalcone, and all trans-chalcone. Representation of the time-dependent mole fraction distribution of these three forms after a pH jump from equilibrated solutions of all-flavylium cation (lower pH values) to higher pH values, shows that formation of trans-chalcone is not completely stochastic (two independent isomerizations), the isomerization of one flavylium showing a small influence on the isomerization of the other. The radical of the methyl viologen bridge is formed upon reduction of the bis(trans-chalcone) with dithionite. The system is reversible after addition of an oxidant in spite of the occurrence of some decomposition. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Conversion of iodine to fluorine-18 based on iodinated chalcone and evaluation for β-amyloid PET imaging.

PubMed

Kaide, Sho; Ono, Masahiro; Watanabe, Hiroyuki; Shimizu, Yoichi; Nakamoto, Yuji; Togashi, Kaori; Yamaguchi, Aiko; Hanaoka, Hirofumi; Saji, Hideo

2018-07-23

In the amyloid cascade hypothesis, β-amyloid (Aβ) plaques is one of the major pathological biomarkers in the Alzheimer's disease (AD) brain. We report the synthesis and evaluation of novel radiofluorinated chalcones, [ 18 F]4-dimethylamino-4'-fluoro-chalcone ([ 18 F]DMFC) and [ 18 F]4'-fluoro-4-methylamino-chalcone ([ 18 F]FMC), as Aβ imaging probes. The conversion of iodine directly introduced to the chalcone backbone into fluorine was successfully carried out by 18 F-labeling via the corresponding boronate precursors, achieving the direct introduction of fluorine-18 into the chalcone backbone to prepare [ 18 F]DMFC and [ 18 F]FMC. In a biodistribution study using normal mice, [ 18 F]DMFC and [ 18 F]FMC showed a higher initial uptake (4.43 and 5.47% ID/g at 2 min postinjection, respectively) into and more rapid clearance (0.52 and 0.66% ID/g at 30 min postinjection, respectively) from the brain than a Food and Drug Administration (FDA)-approved Aβ imaging agent ([ 18 F]Florbetapir), meaning the improvement of the probability of detecting Aβ plaques and the reduction of non-specific binding in the brain. In the in vitro binding studies using aggregates of recombinant Aβ peptides, [ 18 F]DMFC and [ 18 F]FMC showed high binding affinity to recombinant Aβ aggregates at the K d values of 4.47 and 6.50 nM, respectively. In the in vitro autoradiography (ARG) experiment with AD brain sections, [ 18 F]DMFC and [ 18 F]FMC markedly accumulated only in a region with abundant Aβ plaques, indicating that they clearly recognized human Aβ plaques in vitro. These encouraging results suggest that [ 18 F]DMFC and [ 18 F]FMC may be promising PET probes for the detection of an amyloid pathology and the early diagnosis of AD with marked accuracy. Copyright © 2018 Elsevier Ltd. All rights reserved.

Synthesis and Hydrogenation of Disubstituted Chalcones: A Guided-Inquiry Organic Chemistry Project

ERIC Educational Resources Information Center

Mohrig, Jerry R.; Hammond, Christina Noring; Schatz, Paul F.; Davidson, Tammy A.

2009-01-01

Guided-inquiry experiments offer the same opportunities to participate in the process of science as classical organic qualitative analysis used to do. This three-week guided-inquiry project involves an aldol-dehydration synthesis of a chalcone chosen from a set of nine, followed by a catalytic transfer hydrogenation reaction using ammonium formate…

Structure elucidation and DFT-study on substrate-selective formation of chalcones containing ferrocene and phenothiazine units. Study on ferrocenes, Part 17

NASA Astrophysics Data System (ADS)

Lovász, Tamás; Túrós, György; Găină, Luiza; Csámpai, Antal; Frigyes, Dávid; Fábián, Balázs; Silberg, Ioan A.; Sohár, Pál

2005-09-01

By means of base-catalysed condensation of 1-acyl-/1,1'-diacylferrocenes (acyl dbnd6 formyl or acetyl) with 3-formyl- and 3,7-diacetylphenothiazines a series of novel mono- and bis-chalcones were prepared. The enhanced reactivity of the enolate anions of the mono-chalcone intermediates relative to that of the enolates of the corresponding diacetyl-substituted precursor was interpreted by the electron-releasing effect of the ferrocenyl- or phenothiazinyl group present in the β position of the enone subunit. The structures of the novel products were evidenced by IR, 1H and 13C NMR spectroscopy including 2D-COSY, 2D-HSQC and 2D-HMBC measurements.

The antioxidant activity of some curcuminoids and chalcones.

PubMed

Sökmen, Münevver; Akram Khan, M

2016-06-01

The antioxidant properties of the synthetic compound (C1)-(C8), which comprised 7 curcuminoids and a chalcone, were evaluated by two complementary assays, DPPH and β-carotene/linoleic acid. It was found that, in general, the free radical scavenging ability of (C1)-(C8) was concentration-dependent. Compounds (C1) and (C4), which contained (4-OH) phenolic groups, were found to be highly potent antioxidants with higher antioxidant values than BHT suggesting that synthetic curcuminoids are more potent antioxidants than standard antioxidants like BHT. Using β-carotene-linoleic acid assay, only the water-soluble 2, 4,6-trihydroxyphenolic chalcone (C5) showed 85.2 % inhibition of the formation of conjugated dienes reflecting on its potent antioxidant activity.

Inhibition of fumarate reductase in Leishmania major and L. donovani by chalcones.

PubMed

Chen, M; Zhai, L; Christensen, S B; Theander, T G; Kharazmi, A

2001-07-01

Our previous studies have shown that chalcones exhibit potent antileishmanial and antimalarial activities in vitro and in vivo. Preliminary studies showed that these compounds destroyed the ultrastructure of Leishmania parasite mitochondria and inhibited the respiration and the activity of mitochondrial dehydrogenases of Leishmania parasites. The present study was designed to further investigate the mechanism of action of chalcones, focusing on the parasite respiratory chain. The data show that licochalcone A inhibited the activity of fumarate reductase (FRD) in the permeabilized Leishmania major promastigote and in the parasite mitochondria, and it also inhibited solubilized FRD and a purified FRD from L. donovani. Two other chalcones, 2,4-dimethoxy-4'-allyloxychalcone (24m4ac) and 2,4-dimethoxy-4'-butoxychalcone (24mbc), also exhibited inhibitory effects on the activity of solubilized FRD in L. major promastigotes. Although licochalcone A inhibited the activities of succinate dehydrogenase (SDH), NADH dehydrogenase (NDH), and succinate- and NADH-cytochrome c reductases in the parasite mitochondria, the 50% inhibitory concentrations (IC(50)) of licochalcone A for these enzymes were at least 20 times higher than that for FRD. The IC(50) of licochalcone A for SDH and NDH in human peripheral blood mononuclear cells were at least 70 times higher than that for FRD. These findings indicate that FRD, one of the enzymes of the parasite respiratory chain, might be the specific target for the chalcones tested. Since FRD exists in the Leishmania parasite and does not exist in mammalian cells, it could be an excellent target for antiprotozoal drugs.

Acarbose versus trans-chalcone: comparing the effect of two glycosidase inhibitors on obese mice.

PubMed

Jalalvand, Fatemeh; Amoli, Mahsa M; Yaghmaei, Parichehreh; Kimiagar, Masoud; Ebrahim-Habibi, Azadeh

2015-06-01

Acarbose and trans-chalcone are glucosidase inhibitors whose beneficial effects have been demonstrated in diabetes. The present study aimed at investigating their potential effects in obesity. NMRI male mice (n = 48) were subjected to a high fat diet for four weeks, which induced an initial state of obesity. One control group was given normal rodent diet. Obese animals were then switched to normal rodent diet, and divided to four groups (n = 12 in each): untreated, sham (receiving grape seed oil), and experimental groups receiving acarbose and trans-chalcone (12 mg/kg) during eight weeks. Body weight, blood glucose and other biochemical parameters including triglycerides (TG), cholesterol, HDL, AST, and ALT were measured, as well as leptin, adiponectin, TNF-α, and total antioxidant capacity (TAC). Histological studies were performed on adipose cells and liver tissue samples. All factors were affected in a positive manner by acarbose, save for body weight, blood sugar and leptin levels, on which acarbose effects, although observable, were not statistically significant. Grape seed oil, used as a solvent for trans-chalcone was found to possess significant effect on TG and TAC, and had beneficial effects on other factors including liver enzymes and cholesterol. Trans-chalcone effects were significant on HDL, leptin and ALT. All compounds seemed to be able to affect fat deposition in liver tissue, and decrease the size of adipose tissue cells to some extent. In conclusion, the tested compounds were able to affect lipid accumulation in tissues and influence adipokines, which may result in an enhanced state with regard to inflammation and oxidative stress.

The influence of the push-pull effect and a π-conjugated system in conversion efficiency of bis-chalcone compounds in a dye sensitized solar cell

NASA Astrophysics Data System (ADS)

Teo, Kien Yung; Tiong, Mee Hing; Wee, Hung Yee; Jasin, Nornadia; Liu, Zhi-Qiang; Shiu, Ming Yang; Tang, Jyun Yang; Tsai, Jenn-Kai; Rahamathullah, Rafizah; Khairul, Wan M.; Tay, Meng Guan

2017-09-01

Chalcone and its related compounds are known to be π-conjugated compounds, which can be potentially used in different electronic areas include dye sensitized solar cell (DSSC). A total of six bis-chalcone compounds (1-6) have been synthesized using a Claisen-Schmidt condensation method under basic conditions. The compounds were used as the dye in DSSC to test their solar conversion efficiency. In the process of solar cell fabrication, titanium(II) oxide (TiO2) coated glass was used as the working electrode, whereas the mixture of iodine (I2), lithium iodide (LiI), 4-tertbutylpyridine (4-TBP) and 1,2-dimethyl-3-propylimidazolium (DMPII) in 3-methoxypropionitrile were used as the electrolyte. The DSSC was fabricated by immersing the TiO2 glass into the respective bis-chalcone compound solution and dried into the oven at 45 °C for 120 min. Lastly, the working electrode and counter electrode were sealed using surlyn of 60 μm thickness. The efficiency test was conducted under AM 1.5G illumination with the incident light intensity of 100 mW/cm2. Among the six bis-chalcone derivatives, compound 2, namely 1,4-bis-2-hydroxychalcone, was recorded with the highest efficiency (0.054%) compared to the others (0.022-0.035%). The presence of a π-conjugated system and the push-pull effect in the molecule were found to enhance the conversion efficiency of DSSC. Details of the results are discussed in the present paper.

New eco-friendly animal bone meal catalysts for preparation of chalcones and aza-Michael adducts

PubMed Central

2012-01-01

Abstract Two efficient reactions were successfully carried out using Animal Bone Meal (ABM) and potassium fluoride or sodium nitrate doped ABMs as new heterogeneous catalysts under very mild conditions. After preparation and characterization of the catalysts, we first report their use in a simple and convenient synthesis of various chalcones by Claisen–Schmidt condensation and then in an aza-Michael addition involving several synthesized chalcones with aromatic amines. All the reactions were carried out at room temperature in methanol; the chalcone synthesis was also achieved in water environment under microwave irradiation. Doping ABM enhances the rate and yield at each reaction. Catalytic activities are discussed and the ability to re-use the ABM is demonstrated. Results For Claisen–Schmidt the use of ABM alone, yields never exceeded 17%. In each entry, KF/ABM and NaNO3/ABM (79-97%) gave higher yields than using ABM alone under thermic condition. Also the reaction proceeded under microwave irradiation in good yields (72-94% for KF/ABM and 81-97% for NaNO3/ABM) and high purity. For aza-Michael addition the use of ABM doped with KF or NaNO3 increased the catalytic activity remarkably. The very high yields could be noted (84-95% for KF/ABM and 81-94% for NaNO3/ABM). Conclusion The present method is an efficient and selective procedure for the synthesis of chalcones an aza-Michael adducts. The ABM and doped ABMs are a new, inexpensive and attractive solid supports which can contribute to the development of catalytic processes and reduced environmental problems. PMID:22721409

Partial Reconstruction of Flavonoid and Isoflavonoid Biosynthesis in Yeast Using Soybean Type I and Type II Chalcone Isomerases1[w

PubMed Central

Ralston, Lyle; Subramanian, Senthil; Matsuno, Michiyo; Yu, Oliver

2005-01-01

Flavonoids and isoflavonoids are major plant secondary metabolites that mediate diverse biological functions and exert significant ecological impacts. These compounds play important roles in many essential physiological processes. In addition, flavonoids and isoflavonoids have direct but complex effects on human health, ranging from reducing cholesterol levels and preventing certain cancers to improving women's health. In this study, we cloned and functionally characterized five soybean (Glycine max) chalcone isomerases (CHIs), key enzymes in the phenylpropanoid pathway that produces flavonoids and isoflavonoids. Gene expression and kinetics analysis suggest that the soybean type I CHI, which uses naringenin chalcone as substrate, is coordinately regulated with other flavonoid-specific genes, while the type II CHIs, which use a variety of chalcone substrates, are coordinately regulated with an isoflavonoid-specific gene and specifically activated by nodulation signals. Furthermore, we found that some of the newly identified soybean CHIs do not require the 4′-hydroxy moiety on the substrate for high enzyme activity. We then engineered yeast (Saccharomyces cerevisiae) to produce flavonoid and isoflavonoid compounds. When one of the type II CHIs was coexpressed with an isoflavone synthase, the enzyme catalyzing the first committed step of isoflavonoid biosynthesis, various chalcone substrates added to the culture media were converted to an assortment of isoflavanones and isoflavones. We also reconstructed the flavonoid pathway by coexpressing CHI with either flavanone 3β-hydroxylase or flavone synthase II. The in vivo reconstruction of the flavonoid and isoflavonoid pathways in yeast provides a unique platform to study enzyme interactions and metabolic flux. PMID:15778463

Inhibition of Fumarate Reductase in Leishmania major and L. donovani by Chalcones

PubMed Central

Chen, Ming; Zhai, Lin; Christensen, Søren Brøgger; Theander, Thor G.; Kharazmi, Arsalan

2001-01-01

Our previous studies have shown that chalcones exhibit potent antileishmanial and antimalarial activities in vitro and in vivo. Preliminary studies showed that these compounds destroyed the ultrastructure of Leishmania parasite mitochondria and inhibited the respiration and the activity of mitochondrial dehydrogenases of Leishmania parasites. The present study was designed to further investigate the mechanism of action of chalcones, focusing on the parasite respiratory chain. The data show that licochalcone A inhibited the activity of fumarate reductase (FRD) in the permeabilized Leishmania major promastigote and in the parasite mitochondria, and it also inhibited solubilized FRD and a purified FRD from L. donovani. Two other chalcones, 2,4-dimethoxy-4′-allyloxychalcone (24m4ac) and 2,4-dimethoxy-4′-butoxychalcone (24mbc), also exhibited inhibitory effects on the activity of solubilized FRD in L. major promastigotes. Although licochalcone A inhibited the activities of succinate dehydrogenase (SDH), NADH dehydrogenase (NDH), and succinate- and NADH-cytochrome c reductases in the parasite mitochondria, the 50% inhibitory concentrations (IC50) of licochalcone A for these enzymes were at least 20 times higher than that for FRD. The IC50 of licochalcone A for SDH and NDH in human peripheral blood mononuclear cells were at least 70 times higher than that for FRD. These findings indicate that FRD, one of the enzymes of the parasite respiratory chain, might be the specific target for the chalcones tested. Since FRD exists in the Leishmania parasite and does not exist in mammalian cells, it could be an excellent target for antiprotozoal drugs. PMID:11408218

Enhanced pest resistance and increased phenolic production in maize callus transgenically expressing a maize chalcone isomerase -3 like gene

USDA-ARS?s Scientific Manuscript database

Significant losses in maize production are due to damage by insects and ear rot fungi. A gene designated as chalcone-isomerase-like, located in a quantitative trait locus for resistance to Fusarium ear rot fungi, was cloned from a Fusarium ear rot resistant inbred and transgenically expressed in mai...

Antiplasmodial chalcones inhibit sorbitol-induced hemolysis of Plasmodium falciparum-infected erythrocytes.

PubMed

Go, Mei-Lin; Liu, Mei; Wilairat, Prapon; Rosenthal, Philip J; Saliba, Kevin J; Kirk, Kiaran

2004-09-01

A series of alkoxylated and hydroxylated chalcones previously reported to have antiplasmodial activities in vitro were investigated for their effects on the new permeation pathways induced by the malaria parasite in the host erythrocyte membrane. Of 21 compounds with good antiplasmodial activities (50% inhibitory concentrations [IC(50)s], < or = 20 microM), 8 members were found to inhibit sorbitol-induced lysis of parasitized erythrocytes to a significant extent (< or = 40% of control values) at a concentration (10 microM) that was close to their antiplasmodial IC(50)s. Qualitative structure-activity analysis suggested that activity was governed to a greater extent by a substitution on ring B than on ring A of the chalcone template. Most of the active compounds had methoxy or dimethoxy groups on ring B. Considerable variety was permitted on ring A in terms of the electron-donating or -withdrawing property. Lipophilicity did not appear to be an important determinant for activity. Although they are not exceptionally potent as inhibitors (lowest IC(50), 1.9 microM), the chalcones compare favorably with other more potent inhibitors in terms of their selective toxicities against plasmodia and their neutral character.

Synergistic effect of iodide ions on the corrosion inhibition of steel in 0.5 M H 2SO 4 by new chalcone derivatives

NASA Astrophysics Data System (ADS)

Bouklah, M.; Hammouti, B.; Aouniti, A.; Benkaddour, M.; Bouyanzer, A.

2006-07-01

The effect of addition of 4',4-dihydroxychalcone (P 1), 4-aminochalcone (P 2) and 4-bromo, 4'-methoxychalcone (P 3) on the corrosion of steel in 0.5 M sulphuric acid has been studied by weight loss measurements, potentiodynamic and EIS measurements. We investigate the synergistic effect of iodide ions on the corrosion inhibition of steel in the presence of chalcone derivatives. The corrosion rates of the steel decrease with the increase of the chalcones concentration, while the inhibition efficiencies increase. The addition of iodide ions enhances the inhibition efficiency considerably. The presence of iodide ions increases the degree of surface coverage. The synergism parameters SΘ and SI, calculated from surface coverage and the values of inhibition efficiency, in the case of chalcone derivatives are found to be larger than unity. The enhanced inhibition efficiency in the presence of iodide ions is only due to synergism and there is a definite contribution from the inhibitors molecules. E (%) obtained from the various methods is in good agreement. Polarisation measurements show also that the compounds act as cathodic inhibitors.

Impacts of hydroxylation on the photophysics of chalcones: insights into the relation between the chemical composition and the electronic structure.

PubMed

Kalchevski, Dobromir A; Petrov, Vesselin; Tadjer, Alia; Nenov, Artur

2018-03-28

A combined theoretical/experimental study of the photoreactivity of two flavylium-derived chalcones, 2,4,4'-trihydroxychalcone and 2,4'-dihydroxychalcone, at the multiconfigurational wavefunction level of theory (CASSCF//CASPT2) in vacuo and in an implicit solvent (water, treated as a polarisable continuum) and by means of linear absorption spectroscopy is presented. The photosensitivity of flavium salts is expressed in the ability of their chalcone form to undergo a cis-trans isomerisation which has found application in logical networks. Despite a considerable amount of experimental data documenting the dependence of the isomerisation on solvent, pH and temperature, the knowledge of how chalcones process energy under various conditions at the molecular level is still scarce. On the example of 2,4,4'-trihydroxychalcone we unravel the complex excited state deactivation mechanism in vacuo involving ultrafast decay through conical intersections, formation of twisted intramolecular charge transfer species, intramolecular proton transfer and inter system crossings. Furthermore, we rationalise the observed discrepancies in the linear absorption spectra of 2,4,4'-trihydroxychalcone and 2,4'-dihydroxychalcone, thereby establishing a link between the functionalisation pattern and the observed spectral properties.

Multi-targetable chalcone analogs to treat deadly Alzheimer's disease: Current view and upcoming advice.

PubMed

Zhang, Xu; Rakesh, K P; Bukhari, S N A; Balakrishna, Moku; Manukumar, H M; Qin, Hua-Li

2018-06-05

The complications of Alzheimer's disease AD were deadly dangerous cause of neurodegenerative disorders connected with the decline of the cognitive functions and loss of memory. The common form of dementia is accounted as the sixth leading cause of the death affecting any stage of people in a lifetime. Synthetic natural chalcone analogs were currently a hot research topic for the treatment of (AD) which has affected millions of peoples throughout the world. The present aim was set to understand the important problems of the AD and its treatment based on natural derivatives of novel chalcones. One interesting strategy currently of searching for the treatment of AD is to find inhibitors for acetylcholinesterase (AChE) and using metal chelators to target amyloid-β (Aβ) peptides, and then metal-Aβ complexes for the AD pathogenesis. The present compressed review focuses and highlights the design and synthesis of new approaches for the construction of important chalcones playing multiple beneficiary roles in the AD treatments. These hallmarks of concurred research represent the immediate needs of development of novel therapeutic drugs for effective treatment of ADs by understanding the specific pharmacology targets. Copyright © 2018 Elsevier Inc. All rights reserved.

Cytoprotective effects of chalcones from Zuccagnia punctata and melatonin on the gastroduodenal tract in rats.

PubMed

de la Rocha, N; María, A O M; Gianello, J C; Pelzer, L

2003-07-01

The effects of 2',4'-dihydroxychalcone and 2',4'-dihydroxy-3'-methoxychalcone from Zuccagnia punctata Cav. (Fabaceae) and melatonin administration on ethanol-induced gastroduodenal injury were investigated in rats. Both chalcones showed significant preventive effects in treatment with melatonin previous to the necrotising agent. These effects could be due, in part, to the radical scavenging activity of the melatonin.

Design, synthesis, molecular docking and biological evaluation of new dithiocarbamates substituted benzimidazole and chalcones as possible chemotherapeutic agents.

PubMed

Bacharaju, Keerthana; Jambula, Swathi Reddy; Sivan, Sreekanth; Jyostnatangeda, Saritha; Manga, Vijjulatha

2012-05-01

A series of novel dithiocarbamates with benzimidazole and chalcone scaffold have been designed synthesised and evaluated for their antimitotic activity. Compounds 4c and 9d display the most promising antimitotic activity with IC(50) of 1.66 μM and 1.52 μM respectively. Copyright © 2012 Elsevier Ltd. All rights reserved.

Domain analysis of 3 Keto Acyl-CoA synthase for structural variations in Vitis vinifera and Oryza brachyantha using comparative modelling.

PubMed

Sagar, Mamta; Pandey, Neetesh; Qamar, Naseha; Singh, Brijendra; Shukla, Akanksha

2015-03-01

The long chain fatty acids incorporated into plant lipids are derived from the iterative addition of C2 units which is provided by malonyl-CoA to an acyl-CoA after interactions with 3-ketoacyl-CoA synthase (KCS), found in several plants. This study provides functional characterization of three 3 ketoacyl CoA synthase like proteins in Vitis vinifera (one) and Oryza brachyantha (two proteins). Sequence analysis reveals that protein of Oryza brachyantha shows 96% similarity to a hypothetical protein in Sorghum bicolor; total 11 homologs were predicted in Sorghum bicolor. Conserved domain prediction confirm the presence of FAE1/Type III polyketide synthase-like protein, Thiolase-like, subgroup; Thiolase-like and 3-Oxoacyl-ACP synthase III, C-terminal and chalcone synthase like domain but very long chain 3-keto acyl CoA domain is absent. All three proteins were found to have Chalcone and stilbene synthases C terminal domain which is similar to domain of thiolase and β keto acyl synthase. Its N terminal domain is absent in J3M9Z7 protein of Oryza brachyantha and F6HH63 protein of Vitis vinifera. Differences in N-terminal domain is responsible for distinguish activity. The J3MF16 protein of Oryza brachyantha contains N terminal domain and C terminal domain and characterized using annotation of these domains. Domains Gcs (streptomyces coelicolor) and Chalcone-stilbene synthases (KAS) in 2-pyrone synthase (Gerbera hybrid) and chalcone synthase 2 (Medicago sativa) were found to be present in three proteins. This similarity points toward anthocyanin biosynthetic process. Similarity to chalcone synthase 2 reveals its possible role in Naringenine and Chalcone synthase like activity. In 3 keto acyl CoA synthase of Oryza brachyantha. Active site residues C-240, H-407, N-447 are present in J3MF16 protein that are common in these three protein at different positions. Structural variations among dimer interface, product binding site, malonyl-CoA binding sites, were predicted in localized combination of conserved residues.

Optical nonlinearity of D-A-π-D and D-A-π-A type of new chalcones for potential applications in optical limiting and density functional theory studies

NASA Astrophysics Data System (ADS)

Chandra Shekhara Shetty, T.; Chidan Kumar, C. S.; Gagan Patel, K. N.; Chia, Tze Shyang; Dharmaprakash, S. M.; Ramasami, Ponnadurai; Umar, Yunusa; Chandraju, Siddegowda; Quah, Ching Kheng

2017-09-01

Two new chalcones namely, (2E)-1-(3-fluoro-4-methoxyphenyl)-3-(4-methoxyphenyl) prop-2-en-1-one and (2E)-3-(4-chlorophenyl)-1-(3-fluoro-4-methoxyphenyl)prop-2-en-1-one were synthesized and grown as single crystals by slow evaporation technique in methanol. The FTIR spectrum recorded confirms the presence of functional groups in these materials. The molecular conformation of the compounds was achieved by single crystal X-ray diffraction studies. The thermal stability of the crystals was determined from TGA/DSC curve. The third order optical nonlinearity of the chalcone compounds in DMF solution has been carried out using an Nd:YAG laser at 532 nm as the source of excitation. The nonlinear optical response was characterized by measuring the intensity dependent refractive index n2 of the medium using Z-scan technique. It is seen that the molecules exhibit a negative (defocusing) nonlinearity and large nonlinear refractive index of the order of -1.8 × 10-11 esu. The third-order nonlinearity of the studied chalcones is dominated by nonlinear refraction, which leads to strong optical limiting of laser. The result reveals that these two new chalcone molecules would be a promising material for optical limiting applications. In addition, the optimized molecular geometry, vibrational frequencies in gas, and the Molecular Electrostatic Potential (MEP) surface parameters of the two molecules were calculated using DFT/B3LYP method with 6-311++G(d,p) basis set in ground state. All the theoretical calculations were found in good agreement with experimental data.

Transgenic apple plants overexpressing the chalcone 3-hydroxylase gene of Cosmos sulphureus show increased levels of 3-hydroxyphloridzin and reduced susceptibility to apple scab and fire blight.

PubMed

Hutabarat, Olly Sanny; Flachowsky, Henryk; Regos, Ionela; Miosic, Silvija; Kaufmann, Christine; Faramarzi, Shadab; Alam, Mohammed Zobayer; Gosch, Christian; Peil, Andreas; Richter, Klaus; Hanke, Magda-Viola; Treutter, Dieter; Stich, Karl; Halbwirth, Heidi

2016-05-01

Overexpression of chalcone-3-hydroxylase provokes increased accumulation of 3-hydroxyphloridzin in Malus . Decreased flavonoid concentrations but unchanged flavonoid class composition were observed. The increased 3-hydroxyphlorizin contents correlate well with reduced susceptibility to fire blight and scab. The involvement of dihydrochalcones in the apple defence mechanism against pathogens is discussed but unknown biosynthetic steps in their formation hamper studies on their physiological relevance. The formation of 3-hydroxyphloretin is one of the gaps in the pathway. Polyphenol oxidases and cytochrome P450 dependent enzymes could be involved. Hydroxylation of phloretin in position 3 has high similarity to the B-ring hydroxylation of flavonoids catalysed by the well-known flavonoid 3'-hydroxylase (F3'H). Using recombinant F3'H and chalcone 3-hydroxylase (CH3H) from Cosmos sulphureus we show that F3'H and CH3H accept phloretin to some extent but higher conversion rates are obtained with CH3H. To test whether CH3H catalyzes the hydroxylation of dihydrochalcones in planta and if this could be of physiological relevance, we created transgenic apple trees harbouring CH3H from C. sulphureus. The three transgenic lines obtained showed lower polyphenol concentrations but no shift between the main polyphenol classes dihydrochalcones, flavonols, hydroxycinnamic acids and flavan 3-ols. Increase of 3-hydroxyphloridzin within the dihydrochalcones and of epicatechin/catechin within soluble flavan 3-ols were observed. Decreased activity of dihydroflavonol 4-reductase and chalcone synthase/chalcone isomerase could partially explain the lower polyphenol concentrations. In comparison to the parent line, the transgenic CH3H-lines showed a lower disease susceptibility to fire blight and apple scab that correlated with the increased 3-hydroxyphlorizin contents.

Reaction mechanism of chalcone isomerase. pH dependence, diffusion control, and product binding differences.

PubMed

Jez, Joseph M; Noel, Joseph P

2002-01-11

Chalcone isomerase (CHI) catalyzes the intramolecular cyclization of bicyclic chalcones into tricyclic (S)-flavanones. The activity of CHI is essential for the biosynthesis of flavanone precursors of floral pigments and phenylpropanoid plant defense compounds. We have examined the spontaneous and CHI-catalyzed cyclization reactions of 4,2',4',6'-tetrahydroxychalcone, 4,2',4'-trihydroxychalcone, 2',4'-dihydroxychalcone, and 4,2'-dihydroxychalcone into the corresponding flavanones. The pH dependence of flavanone formation indicates that both the non-enzymatic and enzymatic reactions first require the bulk phase ionization of the substrate 2'-hydroxyl group and subsequently on the reactivity of the newly formed 2'-oxyanion during C-ring formation. Solvent viscosity experiments demonstrate that at pH 7.5 the CHI-catalyzed cyclization reactions of 4,2',4',6'-tetrahydroxychalcone, 4,2',4'-trihydroxychalcone, and 2',4'-dihydroxychalcone are approximately 90% diffusion-controlled, whereas cyclization of 4,2'-dihydroxychalcone is limited by a chemical step that likely reflects the higher pK(a) of the 2'-hydroxyl group. At pH 6.0, the reactions with 4,2',4',6'-tetrahydroxychalcone and 4,2',4'-trihydroxychalcone are approximately 50% diffusion-limited, whereas the reactions of both dihydroxychalcones are limited by chemical steps. Comparisons of the 2.1-2.3 A resolution crystal structures of CHI complexed with the products 7,4'-dihydroxyflavanone, 7-hydroxyflavanone, and 4'-hydroxyflavanone show that the 7-hydroxyflavanones all share a common binding mode, whereas 4'-hydroxyflavanone binds in an altered orientation at the active site. Our functional and structural studies support the proposal that CHI accelerates the stereochemically defined intramolecular cyclization of chalcones into biologically active (2S)-flavanones by selectively binding an ionized chalcone in a conformation conducive to ring closure in a diffusion-controlled reaction.

Chalcone-based small-molecule inhibitors attenuate malignant phenotype via targeting deubiquitinating enzymes

PubMed Central

Issaenko, Olga A.; Amerik, Alexander Yu

2012-01-01

The ubiquitin-proteasome system (UPS) is usurped by many if not all cancers to regulate their survival, proliferation, invasion, angiogenesis and metastasis. Bioflavonoids curcumin and chalcones exhibit anti-neoplastic selectivity through inhibition of the 26S proteasome-activity within the UPS. Here, we provide evidence for a novel mechanism of action of chalcone-based derivatives AM146, RA-9 and RA-14, which exert anticancer activity by targeting deubiquitinating enzymes (DUB) without affecting 20S proteasome catalytic-core activity. The presence of the α,β-unsaturated carbonyl group susceptible to nucleophilic attack from the sulfhydryl of cysteines in the active sites of DUB determines the capacity of novel small-molecules to act as cell-permeable, partly selective DUB inhibitors and induce rapid accumulation of polyubiquitinated proteins and deplete the pool of free ubiquitin. These chalcone-derivatives directly suppress activity of DUB UCH-L1, UCH-L3, USP2, USP5 and USP8, which are known to regulate the turnover and stability of key regulators of cell survival and proliferation. Inhibition of DUB-activity mediated by these compounds downregulates cell-cycle promoters, e.g., cyclin D1 and upregulates tumor suppressors p53, p27Kip1 and p16Ink4A. These changes are associated with arrest in S-G2/M, abrogated anchorage-dependent growth and onset of apoptosis in breast, ovarian and cervical cancer cells without noticeable alterations in primary human cells. Altogether, this work provides evidence of antitumor activity of novel chalcone-based derivatives mediated by their DUB-targeting capacity; supports the development of pharmaceuticals to directly target DUB as a most efficient strategy compared with proteasome inhibition and also provides a clear rationale for the clinical evaluation of these novel small-molecule DUB inhibitors. PMID:22510564

Monoamine oxidase inhibitory activity of methoxy-substituted chalcones.

PubMed

Mathew, Bijo; Mathew, Githa Elizabeth; Ucar, Gulberk; Joy, Monu; Nafna, E K; Lohidakshan, Krishnakumar K; Suresh, Jerad

2017-11-01

The MAO-B inhibitory activity of chalcone (1, 3- diphenyl-2-propen-1-one) based compounds arise from its structural similarity with 1, 4-diphenyl-2-butene, a known MAO-B inhibitor. Based on our previous report, the methoxy-substituted with fluorine containing chalcones are promising reversible MAO-B inhibitors, while in the present study, a series of methoxylated chalcones (C1-C9) bearing substitution on the para position of ring B was synthesized and evaluated for their human monoamine oxidase inhibitory activity. With the exception of (2E)-1-(4-methoxyphenyl)-3-(4-nitrophenyl) prop-2-en-1-one (C7), which is a nonselective inhibitor, the chalcones exhibited competitive, selective, and reversible inhibition of hMAO-B. The most potent compound, (2E)-3-[4-(dimethylamino) phenyl]-1-(4-methoxyphenyl) prop-2-en-1-one (C5), showed the best inhibitory activity towards hMAO-B (IC 50 =0.29±0.011μM;K i =0.14±0.001μM). The reversibility of MAO-B inhibition by compound C5 was demonstrated by the recovery of enzyme activity after dialysis of mixtures containing enzyme and inhibitor. The reversiblity of C5 was 25.38±1.40 and 92.00±3.87% before and after dialysis, respectively. PAMPA was carried out to evaluate the blood-brain barrier effects of the designated compounds. Moreover, the most potent MAO-B inhibitor, C5, was found to be nontoxic towards cultured hepatic cells at 5 and 25μM, with 97 and 90% viability. Molecular docking study was performed against hMAO-B to observe the binding site interactions of the lead compound. Copyright © 2017 Elsevier B.V. All rights reserved.

Cholinesterases inhibition and molecular modeling studies of piperidyl-thienyl and 2-pyrazoline derivatives of chalcones.

PubMed

Shah, Muhammad Shakil; Khan, Shafi Ullah; Ejaz, Syeda Abida; Afridi, Saifullah; Rizvi, Syed Umar Farooq; Najam-Ul-Haq, Muhammad; Iqbal, Jamshed

2017-01-22

Super-activation of cholinesterases (acetylcholinesterase and butyrylcholinesterase) are linked to various neurological problems most precisely Alzheimer's disease (AD), which leads to senile dementia. Therefore, cholinesterases (AChE & BChE) inhibition are considered as a promising strategy for the treatment of Alzheimer's disease. FDA approved drugs for the treatment of AD, belong to a group of cholinesterase inhibitors. However, none of them is able to combat or completely abrogate the disease progression. Herein, we report a series of newly synthesized chalcone derivatives with anti-AD potential. For this purpose, a series of piperidyl-thienyl and 2-pyrazoline derivatives of chalcones were tested for their cholinesterases (AChE & BChE) inhibitory activity. All compounds were found as selective inhibitor of AChE. In piperidyl chalcones derivatives compound 1e having IC 50 of 0.16 ± 0.008 μM and 2m in 2-pyrazoline chalcones with IC 50 of 0.13 ± 0.006 μM, were found to be the most potent inhibitors of AChE, exhibiting ≈142 and ≈ 173-fold greater inhibitory potential compared to the reference inhibitor i.e., Neostigmine (IC 50  ± SEM = 22.2 ± 3.2 μM). Molecular docking studies of most potent inhibitors were carried out to investigate the binding interactions inside the active site. Molecular docking study revealed that potent compounds and co-crystalized ligand had same binding orientation within the active site of target enzyme. Most of these compounds are selective inhibitors of AChE with a potential use against progressive neurodegenerative disorder and age related problems. Copyright © 2016 Elsevier Inc. All rights reserved.

SNP in Chalcone Synthase gene is associated with variation of 6-gingerol content in contrasting landraces of Zingiber officinale.Roscoe.

PubMed

Ghosh, Subhabrata; Mandi, Swati Sen

2015-07-25

Zingiber officinale, medicinally the most important species within Zingiber genus, contains 6-gingerol as the active principle. This compound obtained from rhizomes of Z.officinale, has immense medicinal importance and is used in various herbal drug formulations. Our record of variation in content of this active principle, viz. 6-gingerol, in land races of this drug plant collected from different locations correlated with our Gene expression studies exhibiting high Chalcone Synthase gene (Chalcone Synthase is the rate limiting enzyme of 6-gingerol biosynthesis pathway) expression in high 6-gingerol containing landraces than in the low 6-gingerol containing landraces. Sequencing of Chalcone Synthase cDNA and subsequent multiple sequence alignment revealed seven SNPs between these contrasting genotypes. Converting this nucleotide sequence to amino acid sequence, alteration of two amino acids becomes evident; one amino acid change (asparagine to serine at position 336) is associated with base change (A→G) and another change (serine to leucine at position 142) is associated with the base change (C→T). Since asparagine at position 336 is one of the critical amino acids of the catalytic triad of Chalcone Synthase enzyme, responsible for substrate binding, our study suggests that landraces with a specific amino acid change viz. Asparagine (found in high 6-gingerol containing landraces) to serine causes low 6-gingerol content. This is probably due to a weak enzyme substrate association caused by the absence of asparagine in the catalytic triad. Detailed study of this finding could also help to understand molecular mechanism associated with variation in 6-gingerol content in Z.officinale genotypes and thereby strategies for developing elite genotypes containing high 6-gingerol content. Copyright © 2015 Elsevier B.V. All rights reserved.

Effects of structural modifications on the metal binding, anti-amyloid activity, and cholinesterase inhibitory activity of chalcones.

PubMed

Fosso, Marina Y; LeVine, Harry; Green, Keith D; Tsodikov, Oleg V; Garneau-Tsodikova, Sylvie

2015-09-28

As the number of individuals affected with Alzheimer's disease (AD) increases and the availability of drugs for AD treatment remains limited, the need to develop effective therapeutics for AD becomes more and more pressing. Strategies currently pursued include inhibiting acetylcholinesterase (AChE) and targeting amyloid-β (Aβ) peptides and metal-Aβ complexes. This work presents the design, synthesis, and biochemical evaluation of a series of chalcones, and assesses the relationship between their structures and their ability to bind metal ions and/or Aβ species, and inhibit AChE/BChE activity. Several chalcones were found to exhibit potent disaggregation of pre-formed N-biotinyl Aβ1-42 (bioAβ42) aggregates in vitro in the absence and presence of Cu(2+)/Zn(2+), while others were effective at inhibiting the action of AChE.

Nonlinear optical studies and structure-activity relationship of chalcone derivatives with in silico insights

NASA Astrophysics Data System (ADS)

Kar, Swayamsiddha; Adithya, K. S.; Shankar, Pruthvik; Jagadeesh Babu, N.; Srivastava, Sailesh; Nageswara Rao, G.

2017-07-01

Nine chalcones were prepared via Claisen-Schmidt condensation, and characterized by UV-vis, IR, 1H NMR, 13C NMR and mass spectrometry. One of the representative member 4-NDM-TC has been studied via single crystal XRD and the TGA/DTA technique. SHG efficiency and NLO susceptibilities of the chalcones have been evaluated by the Kurtz and Perry method and Degenerate Four Wave Mixing techniques respectively. 3-Cl-4‧-HC was noted to possess SHG efficiency 1.37 times that of urea while 4-NDM-TC returned the highest third order NLO susceptibilities with respect to CS2. In silico studies help evaluate various physical parameters, in correlating the observed activities. In conclusion, the structure-activity relationship was derived based on the in silico and experimental results for the third order NLO susceptibilities.

"N"-Heterocyclic Carbene-Catalyzed Reaction of Chalcone and Cinnamaldehyde to Give 1,3,4-Triphenylcyclopentene Using Organocatalysis to Form a Homoenolate Equivalent

ERIC Educational Resources Information Center

Snider, Barry B.

2015-01-01

In this experiment, students carry out a modern organocatalytic reaction using IMes·HCl and NaOH to catalyze the formation of 1,3,4-triphenylcyclopentene from cinnamaldehyde and chalcone in water. Deprotonation of IMes·HCl with NaOH forms the "N"-heterocyclic carbene IMes that reacts with cinnamaldehyde to form a homoenolate equivalent…

Dual emission of chalcone-analogue dyes emitting in the red region

NASA Astrophysics Data System (ADS)

Fayed, Tarek A.; Awad, Mohamed K.

2004-08-01

The photophysical properties of new synthesized chalcones namely; 1-(4 '-R-phenyl)-5-(4 '-dimethylaminophenyl)-2,4- pentadien-1-one, [R=H ( 1), Cl ( 2) and OCH 3 ( 3)] were studied in different solvents by using steady-state absorption and emission spectroscopy. The fluorescence spectra of these chalcones exhibit dual emission in medium and polar solvents. The dual emission was attributed to population of a polar locally excited (LE) state and a highly dipolar intramolecular charge transfer (ICT) state. The changes in dipole moments upon excitation were calculated from the solvatochromic plots. The total fluorescence quantum yields ( φf) were also determined, and their values are strongly dependent on the nature of substitutent and the solvent polarity. Semiempirical molecular orbital calculations using the atom superposition and electron delocalization molecular orbital (ASED-MO) method were also performed to investigate the molecular and electronic structures of these chalcones in both the ground and excited state. The change of the dipole moment upon excitation was explained on the basis of changes in the charge redistribution over the whole skeleton of the molecules, which agree well with the experimental results. Also, the nature and energy of the electronic transitions were elucidated and discussed in relation to the experimental data.

Polyanthumin, a novel cyclobutane chalcone trimmer from Memecylon polyanthum.

PubMed

Chen, Guan; Cui, Cheng-Bin; Qi, Ai-Di; Li, Chang-Wei; Tao, Zun-Wei; Ren, Rong

2015-01-01

A novel unusual trimmer chalcone, polyanthumin (1), together with five known compounds myricetin 3-O-(3″-O-galloyl)-α-l-rhamnopyranoside (2), sulfuretin (3), fustin (4), gallic acid (5), and ethyl gallate (6), was isolated from the dry stems of Memecylon polyanthum H.L. Li. Among them, compound 1 is a new chalcone trimmer with a novel cyclobutane skeleton in nature. Compounds 3 and 4 are flavonoids carrying a single 7-OH in A ring, which provided the first example of these class flavonoids from the family Melastomataceae. In addition, the antitumor activities for 2-4 were reported for the first time in this study. The antitumor effects of the isolated compounds 1-6 in vitro were assayed by the SRB method using human cancer K562 cells, with the inhibition rates ranging from 39.4% to 54.5% at 100 μg/ml. The IC50 values of compounds 1 and 3 for the inhibition of K562 cell proliferation were determined to be 45.4 and 30.5 μg/ml, respectively. To the best of our knowledge, compound 1 was the second sample as chalcone trimer. In addition, the antitumor activities for 2-4 were reported for the first time in this study.

Antivascular and antitumor properties of the tubulin-binding chalcone TUB091.

PubMed

Canela, María-Dolores; Noppen, Sam; Bueno, Oskía; Prota, Andrea E; Bargsten, Katja; Sáez-Calvo, Gonzalo; Jimeno, María-Luisa; Benkheil, Mohammed; Ribatti, Domenico; Velázquez, Sonsoles; Camarasa, María-José; Díaz, J Fernando; Steinmetz, Michel O; Priego, Eva-María; Pérez-Pérez, María-Jesús; Liekens, Sandra

2017-02-28

We investigated the microtubule-destabilizing, vascular-targeting, anti-tumor and anti-metastatic activities of a new series of chalcones, whose prototype compound is (E)-3-(3''-amino-4''-methoxyphenyl)-1-(5'-methoxy-3',4'-methylendioxyphenyl)-2-methylprop-2-en-1-one (TUB091). X-ray crystallography showed that these chalcones bind to the colchicine site of tubulin and therefore prevent the curved-to-straight structural transition of tubulin, which is required for microtubule formation. Accordingly, TUB091 inhibited cancer and endothelial cell growth, induced G2/M phase arrest and apoptosis at 1-10 nM. In addition, TUB091 displayed vascular disrupting effects in vitro and in the chicken chorioallantoic membrane (CAM) assay at low nanomolar concentrations. A water-soluble L-Lys-L-Pro derivative of TUB091 (i.e. TUB099) showed potent antitumor activity in melanoma and breast cancer xenograft models by causing rapid intratumoral vascular shutdown and massive tumor necrosis. TUB099 also displayed anti-metastatic activity similar to that of combretastatin A4-phosphate. Our data indicate that this novel class of chalcones represents interesting lead molecules for the design of vascular disrupting agents (VDAs). Moreover, we provide evidence that our prodrug approach may be valuable for the development of anti-cancer drugs.

Antivascular and antitumor properties of the tubulin-binding chalcone TUB091

PubMed Central

Canela, María-Dolores; Noppen, Sam; Bueno, Oskía; Prota, Andrea E.; Bargsten, Katja; Sáez-Calvo, Gonzalo; Jimeno, María-Luisa; Benkheil, Mohammed; Ribatti, Domenico; Velázquez, Sonsoles; Camarasa, María-José; Fernando Díaz, J.; Steinmetz, Michel O.; Priego, Eva-María; Pérez-Pérez, María-Jesús; Liekens, Sandra

2017-01-01

We investigated the microtubule-destabilizing, vascular-targeting, anti-tumor and anti-metastatic activities of a new series of chalcones, whose prototype compound is (E)-3-(3’’-amino-4’’-methoxyphenyl)-1-(5’-methoxy-3’,4’-methylendioxyphenyl)-2-methylprop-2-en-1-one (TUB091). X-ray crystallography showed that these chalcones bind to the colchicine site of tubulin and therefore prevent the curved-to-straight structural transition of tubulin, which is required for microtubule formation. Accordingly, TUB091 inhibited cancer and endothelial cell growth, induced G2/M phase arrest and apoptosis at 1-10 nM. In addition, TUB091 displayed vascular disrupting effects in vitro and in the chicken chorioallantoic membrane (CAM) assay at low nanomolar concentrations. A water-soluble L-Lys-L-Pro derivative of TUB091 (i.e. TUB099) showed potent antitumor activity in melanoma and breast cancer xenograft models by causing rapid intratumoral vascular shutdown and massive tumor necrosis. TUB099 also displayed anti-metastatic activity similar to that of combretastatin A4-phosphate. Our data indicate that this novel class of chalcones represents interesting lead molecules for the design of vascular disrupting agents (VDAs). Moreover, we provide evidence that our prodrug approach may be valuable for the development of anti-cancer drugs. PMID:27224920

2',5'-Dihydroxychalcone as a potent chemical mediator and cyclooxygenase inhibitor.

PubMed

Lin, C N; Lee, T H; Hsu, M F; Wang, J P; Ko, F N; Teng, C M

1997-05-01

Eleven chalcone derivatives have been tested for their inhibitory effects on platelet aggregation in rabbit platelet suspension and the activation of mast cells and neutrophils. Arachidonic acid-induced platelet aggregation was potently inhibited by almost all the compounds and some also had a potent inhibitory effect on collagen-induced platelet aggregation and cyclooxygenase. Some hydroxychalcone derivatives showed strong inhibitory effects on the release of beta-glucuronidase and lysozyme, and on superoxide formation by rat neutrophils stimulated with the peptide fMet-Leu-Phe (fMLP). We found that the anti-inflammatory effect of 2',5'-dihydroxychalcone was greater than that of trifluoperazine. 2'5'-Dihydroxy and 2',3,4,5'-tetrahydroxyl chalcones, even at low concentration (50 microM), tested in platelet-rich plasma from man almost completely inhibited secondary aggregation induced by adrenaline. These results suggest that the anti-platelet effects of the chalcones are mainly a result of inhibition of thromboxane formation.

Cytotoxic effect of butein on human colon adenocarcinoma cell proliferation.

PubMed

Yit, C C; Das, N P

1994-07-15

Several classes of plant polyphenols namely, flavonoids, chalcones and coumarins exhibited varying degrees of inhibition on the cell proliferation of human colon adenocarcinoma cell line 220.1. At the highest concentration tested (100 microM), many of the chalcones showed > 100% growth inhibition and their order of potency was butein > 2'-hydroxychalcone > 2-hydroxychalcone > 2',6'-dihydroxy-4'-methoxychalcone > 2',4-dihydroxychalcone with IC50 values of 1.75, 6.2, 7.5, 17, 23 microM, respectively. Butein (the most potent chalcone) at 2 microM concentration inhibited the incorporation of 14C-labelled thymidine, uridine and leucine into the colon cancer cells whilst 5-fluorouracil (5-FU, a chemotherapeutic drug) at 50 microM concentration could significantly inhibit only the uridine incorporation. The mode of cytotoxic action of butein was different from 5-FU but may be similar to colchicine, a known HeLa cell inhibitor.

Substitution effect on a hydroxylated chalcone: Conformational, topological and theoretical studies

NASA Astrophysics Data System (ADS)

Custodio, Jean M. F.; Vaz, Wesley F.; de Andrade, Fabiano M.; Camargo, Ademir J.; Oliveira, Guilherme R.; Napolitano, Hamilton B.

2017-05-01

The effect of substituents on two hydroxylated chalcones was studied in this work. The first chalcone, with a dimethylamine group (HY-DAC) and the second, with three methoxy groups (HY-TRI) were synthesized and crystallized from ethanol on centrosymmetric space group P21/c. The geometric parameters and supramolecular arrangement for both structures obtained from single crystal X-ray diffraction data were analyzed. The intermolecular interactions were investigated by Hirshfeld surfaces with their respective 2D plot for quantification of each type of contact. Additionally, the observed interactions were characterized by QTAIM analysis, and DFT calculations were applied for theoretical vibrational spectra, localization and quantification of frontier orbitals and potential electrostatic map. The flatness of both structures was affected by the substituents, which led to different monoclinic crystalline packing. The calculated harmonic vibrational frequencies and homo-lumo gap confirmed the stability of the structures, while intermolecular interactions were confirmed by potential electrostatic map and QTAIM analysis.

Synthesis, in Vivo Anti-inflammatory, and in Vitro Antimicrobial Activity of New 5-Benzofuranyl Fused Pyrimidines.

PubMed

Nassar, Ekhlass; El-Badry, Yaser Abdel-Moemen; El Kazaz, Hagar

2016-01-01

Chalcone (3) has been synthesized as a new chalcone derivative bearing benzofuran moiety at 1 position. Such chalcone was used as a model dielectrophile applied to react with some nucleophiles such as 5-amino pyrazoles, 5-amino-1,2,4-triazole, 2-aminobenzimidazole, and 6-uraciles under Michael reaction conditions and resulted in a new series of fused pyrimidines such as pyrazolo[1,5-a]pyrimidines 7a-e, [1,2,4]-triazolo[1,5-a]pyrimidine 9, pyrimido[1,2-a]benzimidazole 11, and synthesis of pyrido[2,3-d]pyrimidinones 13a and b. The structures of the synthesized target heterocyclic compounds were confirmed by microanalytical and spectral data such as Fourier transform (FT)-IR, (1)H-NMR, and MS spectra. The newly synthesized compounds were evaluated for their anti-inflammatory and antimicrobial activities; most showed significant activities.

A new chalcone from Pongamia pinnata and its antioxidant properties.

PubMed

Ghosh, Anindita; Mandal, Suvra; Banerji, Avijit; Kar, Manoj; Banerji, Julie

2009-02-01

The root bark of Pongamia pinnata Pierre [syn P. glabra (family: Fabaceae)] afforded a new chalcone (karanjapin) and two known flavonoids, a pyranoflavonoid (karanjachromene) and a furanoflavonoid (karanjin) The structure of karanjapin has been established from extensive 2D NMR spectral studies as beta,2'-dihydroxy-a,4'-dimethoxy-3,4-methylenedioxychalcone. Karanjapin and karanjachromene were found to possess significant antioxidant activity. This may play an important role in the pathogenesis of several diseases.

Selective photoinactivation of Histoplasma capsulatum by water-soluble derivatives chalcones.

PubMed

Melo, Wanessa C M A; Santos, Mariana Bastos Dos; Marques, Beatriz de Carvalho; Regasini, Luis Octávio; Giannini, Maria José Soares Mendes; Almeida, Ana Marisa Fusco

2017-06-01

Histoplasmosis is a respiratory and systemic disease caused by the dimorphic fungus Histoplasma capsulatum. The clinical features may vary from asymptomatic infections to disseminated severe form depending of patient immunity. The treatment of histoplasmosis can be performed with itraconazole, fluconazole, and in the disseminated forms is used amphotericin B. However, the critical side effects of amphotericin B, the cases of itraconazole therapy failure and the appearance of fluconozole-resistant strains makes necessary the search of new strategies to treat this disease. Antimicrobial photodynamic therapy (aPDT) seems to be a potential candidate once have been show efficacy to inhibit others dimorphic fungi. Although the photosensitizer (PS) chalcone aggregates in biological medium, it has antifungal activity and show a high quantum yield of ROS formation. So, the aim of this study was to obtain the experimental parameters to achieve an acceptable selective chalcone water-soluble derivatives photoinactivation of H. capsulatum comparing with fibroblastic and keratinocytes cells which are the constituents of some potential host tissues. Yeast and cells were incubated with the same chalchones concentrations and short incubation time followed by irradiation with equal dose of light. The best conditions to kill H. capsulatum selectively were very low photosensitizers concentration (1.95μgmL -1 ) incubated by 15min and irradiated with LED 450nm with 24Jcm -2 . Key words: chalcone, Histoplasma capsulatum, aPDT, selectivity. Copyright © 2017 Elsevier B.V. All rights reserved.

Chalcone isomerase cDNA cloning and mRNA induction by fungal elicitor, wounding and infection

PubMed Central

Mehdy, Mona C.; Lamb, Christopher J.

1987-01-01

The environmentally regulated synthesis of phenylpropanoid natural products was studied by examining the expression of the gene encoding chalcone isomerase (CHI). This enzyme catalyzes a step common to the synthesis of flavonoid pigments and isoflavonoid phytoalexins. A λgt11 library was constructed using mRNA from cell cultures of bean (Phaseolus vulgaris L.) treated with fungal elicitor. Two positive clones were obtained by screening 105 recombinants with an antiserum to purified bean CHI. The identity of the cloned sequences was confirmed by hybrid-select translation and the production of antigenic polypeptides from transcripts synthesized in vitro. Addition of elicitor to cell cultures resulted in the rapid accumulation of CHI mRNA, with maximum levels achieved 3–4 h after elicitation. CHI mRNA also accumulated during the natural infection of hypocotyls with the fungal pathogen Colletotrichum lindemuthianum, and in mechanically wounded hypocotyls. The kinetics of accumulation of CHI mRNA in response to these environmental signals were strikingly similar to those of mRNAs encoding two other phenylpropanoid pathway enzymes, phenylalanine ammonialyase and chalcone synthase. In contrast to the multi-gene families encoding these two enzymes, chalcone isomerase is encoded by a single gene which is regulated by several environmental stimuli. ImagesFig. 2.Fig. 3.Fig. 4.Fig. 5.Fig. 6.Fig. 9. PMID:16453768

Synthesis of novel quinoline-based 4,5-dihydro-1H-pyrazoles as potential anticancer, antifungal, antibacterial and antiprotozoal agents.

PubMed

Ramírez-Prada, Jonathan; Robledo, Sara M; Vélez, Iván D; Crespo, María Del Pilar; Quiroga, Jairo; Abonia, Rodrigo; Montoya, Alba; Svetaz, Laura; Zacchino, Susana; Insuasty, Braulio

2017-05-05

A new series of N-substituted 2-pyrazolines 9a-f, 10a-f, 11a-f, 12a-f and 13a-f were obtained from the cyclocondensation reaction of [(7-chloroquinolin-4-yl)amino]chalcones 8a-f with hydrazine hydrate and its derivatives. Fourteen of the synthesized compounds including the starting chalcones were selected by US National Cancer Institute (NCI) for testing their anticancer activity against 60 different human cancer cell lines, with the most important GI 50 values ranging from 0.28 to 11.7 μM (0.13-6.05 μg/mL) and LC 50 values ranging from 2.6 to > 100 μM (1.2 to > 51.7 μg/mL), for chalcones 8a,d and pyrazolines 10c,d. All compounds were assessed for antibacterial activity against wild type and multidrug resistant gram negative and gram positive bacteria, with MIC values ranging from 31.25 to 500 μg/mL. Additionally, the novel compounds were tested for antifungal and antiparasitic properties. Although these compounds showed mild activity against Candida albicans, chalcones 8a and 8e showed high activity against Cryptococcus neoformans with MIC 50  = 7.8 μg/mL. For anti-Plasmodium falciparum activity the 2-pyrazoline 11b was the most active with EC 50  = 5.54 μg/mL. Regarding the activity against Trypanosoma cruzi, compound 10a was highly active with EC 50  = 0.70 μg/mL. Chalcone 8a had good activity against Leishmania panamensis amastigotes with EC 50  = 0.79 μg/mL. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Attenuation of inflammatory response by a novel chalcone protects kidney and heart from hyperglycemia-induced injuries in type 1 diabetic mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fang, Qilu; Diabetes Center and Department of Endocrinology, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang; Wang, Jingying

High glucose-induced inflammatory response in diabetic complications plays an important role in disease occurrence and development. With inflammatory cytokines and signaling pathways as important mediators, targeting inflammation may be a new avenue for treating diabetic complications. Chalcones are a class of natural products with various pharmacological activities. Previously, we identified L2H17 as a chalcone with good anti-inflammatory activity, inhibiting LPS-induced inflammatory response in macrophages. In this study, we examined L2H17's effect on hyperglycemia-induced inflammation both in mouse peritoneal macrophages and a streptozotocin-induced T1D mouse model. Our results indicate that L2H17 exhibits a strong inhibitory effect on the expression of pro-inflammatorymore » cytokines, cell adhesion molecules, chemokines and macrophage adhesion via modulation of the MAPK/NF-κB pathway. Furthermore, in vivo oral administration of L2H17 resulted in a significant decrease in the expression of pro-inflammatory cytokines and cell adhesion molecules, contributing to a reduction of key markers for renal and cardiac dysfunction and improvements in fibrosis and pathological changes in both renal and cardiac tissues of diabetic mice. These findings provide the evidence supporting targeting MAPK/NF-κB pathway may be effective therapeutic strategy for diabetic complications, and suggest that L2H17 may be a promising anti-inflammatory agent with potential as a therapeutic agent in the treatment of renal and cardiac diabetic complications. - Highlights: • Chalcones are a class of natural products with various pharmacological activities. • We identified L2H17 a chalcone with good anti-inflammatory activity. • L2H17 improved histological abnormalities both in diabetic heart and kidney. • L2H17 reduced inflammatory responses in HG-stimulated mouse peritoneal macrophages. • MAPKs/NF-κB pathway may be a promising therapeutic target for diabetic complications.« less

Functional characterization and expression of GASCL1 and GASCL2, two anther-specific chalcone synthase like enzymes from Gerbera hybrida.

PubMed

Kontturi, Juha; Osama, Raisa; Deng, Xianbao; Bashandy, Hany; Albert, Victor A; Teeri, Teemu H

2017-02-01

The chalcone synthase superfamily consists of type III polyketidesynthases (PKSs), enzymes responsible for producing plant secondary metabolites with various biological and pharmacological activities. Anther-specific chalcone synthase-like enzymes (ASCLs) represent an ancient group of type III PKSs involved in the biosynthesis of sporopollenin, the main component of the exine layer of moss spores and mature pollen grains of seed plants. In the latter, ASCL proteins are localized in the tapetal cells of the anther where they participate in sporopollenin biosynthesis and exine formation within the locule. It is thought that the enzymes responsible for sporopollenin biosynthesis are highly conserved, and thus far, each angiosperm species with a genome sequenced has possessed two ASCL genes, which in Arabidopsis thaliana are PKSA and PKSB. The Gerbera hybrida (gerbera) PKS protein family consists of three chalcone synthases (GCHS1, GCHS3 and GCHS4) and three 2-pyrone synthases (G2PS1, G2PS2 and G2PS3). In previous studies we have demonstrated the functions of chalcone synthases in flavonoid biosynthesis, and the involvement of 2-pyrone synthases in the biosynthesis of antimicrobial compounds found in gerbera. In this study we expanded the gerbera PKS-family by functionally characterizing two gerbera ASCL proteins. In vitro enzymatic studies using purified recombinant proteins showed that both GASCL1 and GASCL2 were able to use medium and long-chain acyl-CoA starters and perform two to three condensation reactions of malonyl-CoA to produce tri- and tetraketide 2-pyrones, usually referred to as alpha-pyrones in sporopollenin literature. Both GASCL1 and GASCL2 genes were expressed only in floral organs, with most expression observed in anthers. In the anthers, transcripts of both genes showed strict tapetum-specific localization. Copyright © 2016 Elsevier Ltd. All rights reserved.

2',4-Dihydroxy-3',4',6'-trimethoxychalcone from Chromolaena odorata possesses anti-inflammatory effects via inhibition of NF-κB and p38 MAPK in lipopolysaccharide-activated RAW 264.7 macrophages.

PubMed

Dhar, Rana; Kimseng, Rungruedee; Chokchaisiri, Ratchanaporn; Hiransai, Poonsit; Utaipan, Tanyarath; Suksamrarn, Apichart; Chunglok, Warangkana

2018-02-01

Immune dysregulation has been implicated in the pathogenesis of many diseases. Macrophages play a crucial role contributing to the onset, progression, and resolution of inflammation. Macrophage inflammatory mediators are of considerable interest as potential targets to treat inflammatory diseases. The present study was conducted to elucidate the anti-inflammatory mechanism of 2',4-dihydroxy-3',4',6'-trimethoxychalcone (1), the major chalcone isolated from Chromolaena odorata (L.) R.M.King & H.Rob, against lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 macrophages. Cell viability, nitric oxide (NO), and proinflammatory cytokines of LPS-activated RAW 264.7 cells were measured by MTT, Griess, and ELISA assays, respectively. Cell lysates were subjected to Western blotting for investigation of protein expression. Treatment with the major chalcone 1 significantly attenuated the production of NO and proinflammatory cytokines, tumor necrosis factor-α, interleukin-1β, and interleukin-6 in a dose-dependent manner. The chalcone suppressed nuclear factor-κB (NF-κB) stimulation by preventing activation of inhibitor κB kinase (IKK) α/β, degradation of inhibitor κB (IκB) α, and translocation of p65 NF-κB into the nucleus. Additionally, the chalcone markedly repressed the phosphorylation of p38 mitogen-activated protein kinase (MAPK), but no further inhibition was detected for c-Jun N-terminal activated kinases or extracellular regulated kinases. Thus, suppression of NF-κB and p38 MAPK activation may be the core mechanism underlying the anti-inflammatory activity of 2',4-dihydroxy-3',4',6'-trimethoxychalcone (1). These findings provide evidence that 2',4-dihydroxy-3',4',6'-trimethoxychalcone (1) possesses anti-inflammatory activity via targeting proinflammatory macrophages. This anti-inflammatory chalcone is a promising compound for reducing inflammation.

Effect of stilbene and chalcone scaffolds incorporation in clofibric acid on PPARα agonistic activity.

PubMed

Giampietro, Letizia; D'Angelo, Alessandra; Giancristofaro, Antonella; Ammazzalorso, Alessandra; De Filippis, Barbara; Di Matteo, Mauro; Fantacuzzi, Marialuigia; Linciano, Pasquale; Maccallini, Cristina; Amoroso, Rosa

2014-01-01

In an effort to develop safe and efficacious compounds for the treatment of metabolic disorders, new compounds based on a combination of clofibric acid, the active metabolite of clofibrate, and trans-stilbene, chalcone, and other lipophilic groups were synthesized. They were evaluated for PPARα transactivation activity; all branched derivatives showed an increase of the transcriptional activity of receptor compared to the linear ones. Noteworthy, stilbene and benzophenone branched derivatives activated the PPARα better than clofibric acid.

QTAIM electron density study of natural chalcones

NASA Astrophysics Data System (ADS)

González Moa, María J.; Mandado, Marcos; Cordeiro, M. Natália D. S.; Mosquera, Ricardo A.

2007-09-01

QTAIM atomic and bond properties, ionization potential, and O-H bond dissociation energies calculated at the B3LYP/6-311++G(2d,2p) level indicate the natural chalcones bear a significant radical scavenging activity. However, their ionization potentials indicate they decrease the electron-transfer rate between antioxidant and oxygen that yields the pro-oxidative cations less than other natural antioxidants. Rings A and B display slight and similar positive charges, whereas ring B is involved in exocycle delocalization at a larger extension.

IR and NMR spectral studies of 4-bromo-1-naphthyl chalcones-assessment of substituent effects

NASA Astrophysics Data System (ADS)

Thirunarayanan, G.; Gopalakrishnan, M.; Vanangamudi, G.

2007-07-01

Infrared νCO (cm -1) of s-cis and s-trans frequencies and nuclear magnetic resonance chemical shifts δ1H (ppm) of H-α and H-β, δ13C (ppm) of C-α and C-β data were assigned from their respective spectra of a series of various substituted styryl 4-bromo-1-naphthyl chalcones. These values are correlated with various Hammett substituent constants. From the results of statistical analysis, the effect of substituents can be explained.

Diverse Molecular Targets for Chalcones with Varied Bioactivities

PubMed Central

Zhou, Bo; Xing, Chengguo

2015-01-01

Natural or synthetic chalcones with different substituents have revealed a variety of biological activities that may benefit human health. The underlying mechanisms of action, particularly with respect to the direct cellular targets and the modes of interaction with the targets, have not been rigorously characterized, which imposes challenges to structure-guided rational development of therapeutic agents or chemical probes with acceptable target-selectivity profile. This review summarizes literature evidence on chalcones’ direct molecular targets in the context of their biological activities. PMID:26798565

Influence of functional groups on the photophysical properties of dimethylamino chalcones as laser dyes

NASA Astrophysics Data System (ADS)

Ibnaouf, K. H.; Elzupir, A. O.; AlSalhi, M. S.; Alaamer, Abdulaziz S.

2018-02-01

In this report, a series of 3-(4-(Dimethylamino) phenyl)-1-(4,3 di-substituted phenyl)-(2E) - propen -1-one chalcones was synthesised and examined as optical materials. The influence of functional groups (FG) and solvents on their photophysical properties was investigated. These include absorption, fluorescence, Stokes shift, and amplified spontaneous emission (ASE). The absorption spectra of all compounds showed a wavelength band in the range 404-429 nm, whereas the fluorescence spectra exhibited a band at 470-535 nm. We found that the fluorescence intensity was inversely proportional to the concentration of chalcones. The FGs and solvents had an amazing effect on the photophysical properties of the synthesised materials. Unexpectedly, the electron withdrawing group showed a highly red shift, whereas the electron donating group exhibited a blue shift. Further, these compounds showed large Stokes shifts (up to 5800 cm-1). ASE was observed under pump pulse laser excitation, and the wavelengths were tuned from 509 to 566 nm.

Cytotoxic 3,4,5-trimethoxychalcones as mitotic arresters and cell migration inhibitors

PubMed Central

Salum, Lívia B.; Altei, Wanessa F.; Chiaradia, Louise D.; Cordeiro, Marlon N.S.; Canevarolo, Rafael R.; Melo, Carolina P.S.; Winter, Evelyn; Mattei, Bruno; Daghestani, Hikmat N.; Santos-Silva, Maria Cláudia; Creczynski-Pasa, Tânia B.; Yunes, Rosendo A.; Yunes, José A.; Andricopulo, Adriano D.; Day, Billy W.; Nunes, Ricardo J.; Vogt, Andreas

2013-01-01

Based on classical colchicine site ligands and a computational model of the colchicine binding site on beta tubulin, two classes of chalcone derivatives were designed, synthesized and evaluated for inhibition of tubulin assembly and toxicity in human cancer cell lines. Docking studies suggested that the chalcone scaffold could fit the colchicine site on tubulin in an orientation similar to that of the natural product. In particular, a 3,4,5-trimethoxyphenyl ring adjacent to the carbonyl group appeared to benefit the ligand-tubulin interaction, occupying the same subcavity as the corresponding moiety in colchicine. Consistent with modeling predictions, several 3,4,5-trimethoxychalcones showed improved cytotoxicity to murine acute lymphoblastic leukemia cells compared with a previously described parent compound, and inhibited tubulin assembly in vitro as potently as colchicine. The most potent chalcones inhibited the growth of human leukemia cell lines at nanomolar concentrations, caused microtubule destabilization and mitotic arrest in human cervical cancer cells, and inhibited human breast cancer cell migration in scratch wound and Boyden chamber assays. PMID:23524161

Antidyslipidemic and antioxidant effects of novel Lupeol-derived chalcones.

PubMed

Srivastava, Shishir; Sonkar, Ravi; Mishra, Sunil Kumar; Tiwari, Avinash; Balaramnavar, Vishal M; Balramnavar, Vishal; Mir, Snober; Bhatia, Gitika; Saxena, Anil K; Lakshmi, Vijai

2013-10-01

A series of Lupeol-based chalcones have been synthesized aiming to enhance the therapeutic efficacy of parent compound, the novel compounds were evaluated for their antidyslipidemic activity in triton-WR 1339 induced hyperlipidemic rats. Among the ten synthesized chalcones, the most active K4, K8, and K9 reversed the plasma levels of TC by (24, 25, 27 %), phospholipid by (25, 26, 25 %) and triacylglycerol by (27, 24, 24 %) respectively. In addition, the compounds showed significant in vitro antioxidant activity. The lipid lowering activity of these compounds were mediated through lipoprotein lipase activation (12-21 %) and enhanced post-heparin lipolytic activity (15-16 %). The compounds also displayed noteworthy inhibitory effect on 3-hydroxy-3-methyl-glutaryl reductase activity (in vitro). The in vitro effect of the most active compounds on MDI-induced adipogenesis using 3T3-L1 preadipocytes at 10 and 20 μM concentrations showed significant inhibition (20-32 %) of adipogenesis.

A quantitative analysis of weak intermolecular interactions & quantum chemical calculations (DFT) of novel chalcone derivatives

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chavda, Bhavin R., E-mail: chavdabhavin9@gmail.com; Dubey, Rahul P.; Patel, Urmila H.

The novel chalcone derivatives have widespread applications in material science and medicinal industries. The density functional theory (DFT) is used to optimized the molecular structure of the three chalcone derivatives (M-I, II, III). The observed discrepancies between the theoretical and experimental (X-ray data) results attributed to different environments of the molecules, the experimental values are of the molecule in solid state there by subjected to the intermolecular forces, like non-bonded hydrogen bond interactions, where as isolated state in gas phase for theoretical studies. The lattice energy of all the molecules have been calculated using PIXELC module in Coulomb –London –Paulimore » (CLP) package and is partitioned into corresponding coulombic, polarization, dispersion and repulsion contributions. Lattice energy data confirm and strengthen the finding of the X-ray results that the weak but significant intermolecular interactions like C-H…O, Π- Π and C-H… Π plays an important role in the stabilization of crystal packing.« less

A synthetic chalcone as a potent inducer of glutathione biosynthesis.

PubMed

Kachadourian, Remy; Day, Brian J; Pugazhenti, Subbiah; Franklin, Christopher C; Genoux-Bastide, Estelle; Mahaffey, Gregory; Gauthier, Charlotte; Di Pietro, Attilio; Boumendjel, Ahcène

2012-02-09

Chalcones continue to attract considerable interest due to their anti-inflammatory and antiangiogenic properties. We recently reported the ability of 2',5'-dihydroxychalcone (2',5'-DHC) to induce both breast cancer resistance protein-mediated export of glutathione (GSH) and c-Jun N-terminal kinase-mediated increased intracellular GSH levels. Herein, we report a structure-activity relationship study of a series of 30 synthetic chalcone derivatives with hydroxyl, methoxyl, and halogen (F and Cl) substituents and their ability to increase intracellular GSH levels. This effect was drastically improved with one or two electrowithdrawing groups on phenyl ring B and up to three methoxyl and/or hydroxyl groups on phenyl ring A. The optimal structure, 2-chloro-4',6'-dimethoxy-2'-hydroxychalcone, induced both a potent NF-E2-related factor 2-mediated transcriptional response and an increased formation of glutamate cysteine ligase holoenzyme, as shown using a human breast cancer cell line stably expressing a luciferase reporter gene driven by antioxidant response elements.

[Cochinchinenin--a new chalcone dimer from the Chinese dragon blood].

PubMed

Zhou, Z H; Wang, J L; Yang, C R

2001-03-01

To study the active constituents of Dracaena cochinchinensis (Lour.) S.C. Chen. in the commercial dragon blood. Various column chromatographies with Sephadex L-20 gel, MCI gel and silica gel were employed for the isolation and purification. The structures of compounds were elucidated by spectral analysis. Nine chalcones were isolated from the commercial dragon's blood which was made of D. cochinchinensis (Lour.) S.C. Chen.. By means of spectral data, they were identified as 1-[5-(2,4,4'-trihydroxydihydrochalconyl)]-1- (p-hydroxyphenyl)-3-(2-methoxy-4-hydroxy-phenyl)-propane (1), 2'-methoxysocotrin-5'-ol (2), socotrin-4'-ol (3), 2-methoxy-4, 4'-dihydroxydihydrochalcone (4), 2, 4, 4'-trihydroxy-dihydrochalcone (5), 2, 4, 4'-trihydroxy-6-methoxydihydrochalcone (6), 2', 4', 4-trihydroxychalcone (7), 2-methoxy-4, 4'-dihydroxychalcone (8) and 2'-methoxy-4', 4-dihydroxychalcone (9). Compound 1 is a new chalcone dimer and named as cochinchinenin. Compounds 2-9 were isolated from D. cochinchinensis (Lour.) S.C. Chen. for the first time.

A Synthetic Chalcone as a Potent Inducer of Glutathione Biosynthesis

PubMed Central

Kachadourian, Remy; Day, Brian J.; Pugazhenti, Subbiah; Franklin, Christopher C.; Genoux-Bastide, Estelle; Mahaffey, Gregory; Gauthier, Charlotte; Di Pietro, Attilio; Boumendjel, Ahcène

2014-01-01

Chalcones continue to attract considerable interest due to their anti-inflammatory and antiangiogenic properties. We recently reported the ability of 2′,5′-dihydroxychalcone (2′,5′-DHC) to induce both breast cancer resistance protein-mediated export of glutathione (GSH) and c-Jun N-terminal kinase-mediated increased intracellular GSH levels. Herein, we report a structure–activity relationship study of a series of 30 synthetic chalcone derivatives with hydroxyl, methoxyl, and halogen (F and Cl) substituents and their ability to increase intracellular GSH levels. This effect was drastically improved with one or two electrowithdrawing groups on phenyl ring B and up to three methoxyl and/or hydroxyl groups on phenyl ring A. The optimal structure, 2-chloro-4′,6′-dimethoxy-2′-hydroxychalcone, induced both a potent NF-E2-related factor 2-mediated transcriptional response and an increased formation of glutamate cysteine ligase holoenzyme, as shown using a human breast cancer cell line stably expressing a luciferase reporter gene driven by antioxidant response elements. PMID:22239485

Theoretical and Experimental Study of Inclusion Complexes of β-Cyclodextrins with Chalcone and 2',4'-Dihydroxychalcone.

PubMed

Sancho, Matias I; Andujar, Sebastian; Porasso, Rodolfo D; Enriz, Ricardo D

2016-03-31

The inclusion complexes formed by chalcone and 2',4'-dihydroxychalcone with β-cyclodextrin have been studied combining experimental (phase solubility diagrams, Fourier transform infrared spectroscopy) and molecular modeling (molecular dynamics, quantum mechanics/molecular mechanics calculations) techniques. The formation constants of the complexes were determined at different temperatures, and the thermodynamic parameters of the process were obtained. The inclusion of chalcone in β-cyclodextrin is an exothermic process, while the inclusion of 2',4'-dihydroxychalcone is endothermic. Free energy profiles, derived from umbrella sampling using molecular dynamics simulations, were constructed to analyze the binding affinity and the complexation reaction at a molecular level. Hybrid QM/MM calculations were also employed to obtain a better description of the energetic and structural aspects of the complexes. The intermolecular interactions that stabilize both inclusion complexes were characterized by means of quantum atoms in molecules theory and reduce density gradient method. The calculated interactions were experimentally observed using FTIR.

Synthesis and antiangiogenic activity study of new hop chalcone Xanthohumol analogues.

PubMed

Nuti, Elisa; Bassani, Barbara; Camodeca, Caterina; Rosalia, Lea; Cantelmo, AnnaRita; Gallo, Cristina; Baci, Denisa; Bruno, Antonino; Orlandini, Elisabetta; Nencetti, Susanna; Noonan, Douglas M; Albini, Adriana; Rossello, Armando

2017-09-29

Angiogenesis induction is a hallmark of cancer. Antiangiogenic properties of Xanthohumol (XN), a naturally occurring prenylated chalcone from hops, have been widely reported. Here we describe the synthesis and study the antiangiogenic activity in vitro of a series of XN derivatives, where different substituents on the B-ring of the chalcone scaffold were inserted. The new XN derivatives inhibited human umbilical-vein endothelial cell (HUVEC) proliferation, adhesion, migration, invasion and their ability to form capillary-like structures in vitro at 10 μM concentration. The preliminary results indicate that the phenolic OH group in R, present in natural XN, is not necessary for having antiangiogenic activity. In fact, the most effective compound from this series, 13, was characterized by a para-methoxy group in R and a fluorine atom in R 2 on B-ring. This study paves the way for future development of synthetic analogues of XN to be used as cancer angiopreventive and chemopreventive agents. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Design, synthesis and preliminary structure-activity relationship investigation of nitrogen-containing chalcone derivatives as acetylcholinesterase and butyrylcholinesterase inhibitors: a further study based on Flavokawain B Mannich base derivatives.

PubMed

Liu, Haoran; Fan, Haoqun; Gao, Xiaohui; Huang, Xueqing; Liu, Xianjun; Liu, Linbo; Zhou, Chao; Tang, Jingjing; Wang, Qiuan; Liu, Wukun

2016-08-01

In order to study the structure-activity relationship of Flavokawain B Mannich-based derivatives as acetylcholinesterase (AChE) inhibitors in our recent investigation, 20 new nitrogen-containing chalcone derivatives (4 a-8d) were designed, synthesized, and evaluated for AChE inhibitory activity in vitro. The results suggested that amino alkyl side chain of chalcone dramatically influenced the inhibitory activity against AChE. Among them, compound 6c revealed the strongest AChE inhibitory activity (IC50 value: 0.85 μmol/L) and the highest selectivity against AChE over BuChE (ratio: 35.79). Enzyme kinetic study showed that the inhibition mechanism of compound 6c against AChE was a mixed-type inhibition. The molecular docking assay showed that this compound can both bind with the catalytic site and the peripheral site of AChE.

Chalcone derivatives from the fern Cyclosorus parasiticus and their anti-proliferative activity.

PubMed

Wei, Han; Zhang, Xuenong; Wu, Guanghua; Yang, Xian; Pan, Songwei; Wang, Yanyan; Ruan, Jinlan

2013-10-01

Three new chalcone derivatives, named parasiticins A-C (1-3), were isolated from the leaves of Cyclosorus parasiticus, together with four known chalcones, 5,7-dihydroxy-4-phenyl-8-(3-phenyl-trans-acryloyl)-3,4-dihydro-1-benzopyran-2-one (4), 2'-hydroxy-4',6'-dimethoxychalcone (5), 2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone (6), 2',4'-dihydroxy-6'-methoxy-3'-methylchalcone (7). The chemical structures of the new isolated compounds were elucidated unambiguously by spectroscopic data analysis. The cytotoxic activities of compounds 1-7 were evaluated against six human cancer cell lines in vitro. Compounds 3 and 6 exhibited substantial cytotoxicity against all six cell lines, especially toward HepG2 with the IC₅₀ values of 1.60 and 2.82 μM, respectively. Furthermore, we demonstrated that compounds 3 and 6 could induce apoptosis in the HepG2 cell line, which may contribute significantly to their cytotoxicity. Copyright © 2013 Elsevier Ltd. All rights reserved.

Exploration of chlorinated thienyl chalcones: A new class of monoamine oxidase-B inhibitors.

PubMed

Mathew, Bijo; Haridas, Abitha; Uçar, Gülberk; Baysal, Ipek; Adeniyi, Adebayo A; Soliman, Mahmoud E S; Joy, Monu; Mathew, Githa Elizabeth; Lakshmanan, Baskar; Jayaprakash, Venkatesan

2016-10-01

Chalcone has been reported to be a valid scaffold for the design of monoamine oxidase (MAO) inhibitors. This scenario has amplified the momentum for the discovery of heteroaryl based chalcone MAO inhibitors. In the present study, we have synthesized a series of eleven chlorinated thienyl chalcone derivatives substituted with a different functional groups at the para- position on the ring B and investigated for their ability to inhibit human MAO-A and -B. With the exception of compound (2E)-1-(4-chlorocyclopenta-1,3-dien-1-yl)-3-(4-nitrophenyl)prop-2-en-1-one (TC7), which was a selective MAO-A inhibitor, all the other derivatives inhibited hMAO-B potently and selectively with competitive mode of inhibition. The most potent compound (2E)-1-(4-chlorocyclopenta-1,3-dien-1-yl)-3-(4-ethylphenyl)prop-2-en-1-one (TC6) was found to be the best activity and higher selectivity towards hMAO-B with Ki and SI values of 0.31±0.02μM and 16.84, respectively. All the compounds presented in the current study are completely non-toxic with 74-88% viable cells to hepatic cells at 100μM concentration. Molecular docking and molecular dynamics simulation studies were carried out using Autodock-4.2 and Amber 14 to understand the molecular level interaction and energy relation of MAO isoforms with selective MAO-B inhibitor TC6. Copyright © 2016 Elsevier B.V. All rights reserved.

In-Silico molecular docking and simulation studies on novel chalcone and flavone hybrid derivatives with 1, 2, 3-triazole linkage as vital inhibitors of Plasmodium falciparum dihydroorotate dehydrogenase.

PubMed

Thillainayagam, Mahalakshmi; Malathi, Kullappan; Ramaiah, Sudha

2017-11-27

The structural motifs of chalcones, flavones, and triazoles with varied substitutions have been studied for the antimalarial activity. In this study, 25 novel derivatives of chalcone and flavone hybrid derivatives with 1, 2, 3-triazole linkage are docked with Plasmodium falciparum dihydroorotate dehydrogenase to establish their inhibitory activity against Plasmodium falciparum. The best binding conformation of the ligands at the catalytic site of dihydroorotate dehydrogenase are selected to characterize the best bound ligand using the best consensus score and the number of hydrogen bond interactions. The ligand namely (2E)-3-(4-{[1-(3-chloro-4-fluorophenyl)-1H-1, 2, 3-triazol-4-yl]methoxy}-3-methoxyphenyl-1-(2-hydroxy-4,6-dimethoxyphenyl)prop-2-en-1-one, is one the among the five best docked ligands, which interacts with the protein through nine hydrogen bonds and with a consensus score of five. To refine and confirm the docking study results, the stability of complexes is verified using Molecular Dynamics Simulations, Molecular Mechanics /Poisson-Boltzmann Surface Area free binding energy analysis, and per residue contribution for the binding energy. The study implies that the best docked Plasmodium falciparum dihydroorotate dehydrogenase-ligand complex is having high negative binding energy, most stable, compact, and rigid with nine hydrogen bonds. The study provides insight for the optimization of chalcone and flavone hybrids with 1, 2, 3-triazole linkage as potent inhibitors.

Antioxidant properties of di-tert-butylhydroxylated flavonoids.

PubMed

Lebeau, J; Furman, C; Bernier, J L; Duriez, P; Teissier, E; Cotelle, N

2000-11-01

Epidemiological evidence suggests an inverse relationship between dietary intake of flavonoids and cardiovascular risk. The biological activities of flavonoids are related to their antioxidative effects, but they also can be mutagenic, due to the prooxidant activity of the catechol pattern. To prevent these problems, we synthesized new flavonoids where one or two di-tert-butylhydroxyphenyl (DBHP) groups replaced catechol moiety at position 2 of the benzopyrane heterocycle. Two DBHP moieties can also be arranged in an arylidene structure or one DBHP fixed on a chalcone structure. Position 7 on the flavone and arylidene or position 4 on the chalcone was substituted by H, OCH(3), or OH. New structures were compared with quercetin and BHT in an LDL oxidation system induced by Cu(II) ions. Arylidenes and chalcones had the best activities (ED(50) = 0.86 and 0.21) compared with vitamin E, BHT, and quercetin (ED(50) = 10.0, 7. 4, and 2.3 microM). Activity towards stable free radical 1, 1-diphenyl-2-picryl-hydrazyl (DPPH) was measured by log Z and ECR(50) parameters. Synthesized flavones proved to be poor DPPH radical scavengers, the activity increasing with the number of DBHP units. In contrast, arylidenes and chalcones were stronger DPPH radical scavengers (log Z > 3, 0.3 < ECR(50) < 2.12) than BHT (log Z = 0.75, ECR(50) = 12.56) or quercetin (log Z = 2.76, ECR(50) = 0.43). Unlike quercetin, synthesized compounds neither chelated nor reduced copper, proving that these new flavonoids had no prooxidant activity in vitro.

Regiospecificity of Human UDP-glucuronosyltransferase Isoforms in Chalcone and Flavanone Glucuronidation Determined by Metal Complexation and Tandem Mass Spectrometry

PubMed Central

Niemeyer, Emily D.; Brodbelt, Jennifer S.

2013-01-01

The glucuronidation of a series of chalcones (2'-hydroxychalcone, 2',4'-dihydroxychalcone, 3,2'-dihydroxychalcone, 4,2'-dihydroxychalcone, and cardamonin) and their corresponding cyclized flavanones (7-hydroxyflavanone, 3'-hydroxyflavanone, 4'-hydroxyflavanone, and alpinetin) by nine human UDP-glucuronosyltransferase (UGT) 1A enzymes was evaluated. A post-column metal complexation LC-MS/MS strategy was used successfully to produce characteristic mass spectrometric product ions that were utilized in combination with elution order trends to identify chalcone and flavanone monoglucuronides unambiguously, thus allowing determination of the regioselectivities of the UGT1A isoforms. The presence of hydroxy groups on the A or B-ring had a significant effect on the glucuronide product yield and the site where glucuronidation occurred. For example, for reaction with UGT1A9, formation of the 2'-O-glucuronide was increased for dihydroxychalcones with A-ring hydroxy substituents. In contrast, although UGT1A8 reacted with 3,2'-dihydroxychalcone and 4,2'-dihydroxychalcone to yield 2'-O-glucuronide products, the presence of a B-ring hydroxy group at the 4' position on cardamonin and 2',4'-dihydroxychalcone quenched the reaction at the OH-2' position. Moreover, the A-ring OH-4 group promoted glucuronidation at the 2' position for the reaction of 4,2'-dihydroxychalcone with UGT1A1 and 1A3. For UGT1A7, hydroxy group substituents on the chalcone A-ring also promoted cyclization and formation of the corresponding flavanone glucuronide. PMID:23713759

Regiospecificity of human UDP-glucuronosyltransferase isoforms in chalcone and flavanone glucuronidation determined by metal complexation and tandem mass spectrometry.

PubMed

Niemeyer, Emily D; Brodbelt, Jennifer S

2013-06-28

The glucuronidation of a series of chalcones (2'-hydroxychalcone, 2',4'-dihydroxychalcone, 3,2'-dihydroxychalcone, 4,2'-dihydroxychalcone, and cardamonin) and their corresponding cyclized flavanones (7-hydroxyflavanone, 3'-hydroxyflavanone, 4'-hydroxyflavanone, and alpinetin) by eight human UDP-glucuronosyltransferase (UGT) 1A enzymes was evaluated. A postcolumn metal complexation LC-MS/MS strategy was used successfully to produce characteristic mass spectrometric product ions that were utilized in combination with elution order trends to identify chalcone and flavanone monoglucuronides unambiguously, thus allowing determination of the regioselectivities of the UGT1A isoforms. The presence of hydroxy groups on the A- or B-ring had a significant effect on the glucuronide product yield and the site where glucuronidation occurred. For example, for reaction with UGT1A9, formation of the 2'-O-glucuronide was increased for dihydroxychalcones with A-ring hydroxy substituents. In contrast, although UGT1A8 reacted with 3,2'-dihydroxychalcone and 4,2'-dihydroxychalcone to yield 2'-O-glucuronide products, the presence of a B-ring hydroxy group at the 4' position on cardamonin and 2',4'-dihydroxychalcone quenched the reaction at the OH-2' position. Moreover, the A-ring OH-4 group promoted glucuronidation at the 2' position for the reaction of 4,2'-dihydroxychalcone with UGT1A1 and 1A3. For UGT1A7, hydroxy group substituents on the chalcone A-ring also promoted cyclization and formation of the corresponding flavanone glucuronide.

Aromatic Polyketide Synthases (Purification, Characterization, and Antibody Development to Benzalacetone Synthase from Raspberry Fruits).

PubMed Central

Borejsza-Wysocki, W.; Hrazdina, G.

1996-01-01

p-Hydroxyphenylbutan-2-one, the characteristic aroma compound of raspberries (Rubus idaeus L.), is synthesized from p-coumaryl-coenzyme A and malonyl-coenzyme A in a two-step reaction sequence that is catalyzed by benzalacetone synthase and benzalacetone reductase (W. Borejsza-Wysocki and G. Hrazdina [1994] Phytochemistry 35: 623-628). Benzalacetone synthase condenses one malonate with p-coumarate to form the pathway intermediate p-hydroxyphenylbut-3-ene-2-one (p-hydroxybenzalacetone) in a reaction that is similar to those catalyzed by chalcone and stilbene synthases. We have obtained an enzyme preparation from ripe raspberries that was preferentially enriched in benzalacetone synthase (approximately 170-fold) over chalcone synthase (approximately 14-fold) activity. This preparation was used to characterize benzalacetone synthase and to develop polyclonal antibodies in rabbits. Benzalacetone synthase showed similarity in its molecular properties to chalcone synthase but differed distinctly in its substrate specificity, response to 2-mercaptoethanol and ethylene glycol, and induction in cell-suspension cultures. The product of the enzyme, p-hydroxybenzalacetone, inhibited mycelial growth of the raspberry pathogen Phytophthora fragariae var rubi at 250 [mu]M. We do not know whether the dual activity in the benzalacetone synthase preparation is the result of a bifunctional enzyme or is caused by contamination with chalcone synthase that was also present. The rapid induction of the enzyme in cell-suspension cultures upon addition of yeast extract and the toxicity of its product, p-hydroxybenzalacetone, to phytopathogenic fungi also suggest that the pathway may be part of a plant defense response. PMID:12226219

Introduction of unnatural amino acids into chalcone isomerase.

PubMed

Bednar, R A; McCaffrey, C; Shan, K

1991-01-01

The active site cysteine residue of chalcone isomerase was rapidly and selectively modified under denaturing conditions with a variety of electrophilic reagents. These denatured and modified enzyme were renatured to produce enzyme derivatives containing a series of unnatural amino acids in the active site. Addition of methyl, ethyl, butyl, heptyl, and benzyl groups to the cysteine sulfur does not abolish catalytic activity, although the activity decreases as the steric bulk of the amino acid side-chain increases. Modification of the cysteine to introduce a charged homoglutamate or a neutral homoglutamine analogue results in retention of 22% of the catalytic activity. Addition of a methylthio group (SMe) to the cysteine residue of native chalcone isomerase preserves 85% of the catalytic activity measured with 2',4',4-trihydroxychalcone, 2',4',6',4-tetrahydroxychalcone, or 2'-hydroxy-4-methoxychalcone as substrates. The competitive inhibition constant for 4',4-dihydroxychalcone, the substrate inhibition constant for 2',4',4-trihydroxychalcone, and other steady-state kinetic parameters for the methanethiolated enzyme are very similar to those of the native enzyme. The strong binding of 4',4-dihydroxychalcone to the methanethiolated enzyme shows that there is no steric repulsion between this modified amino acid residue and the substrate analogue. This structure-activity study clearly demonstrates that the active site cysteine residue does not function as an acid-base or nucleophilic group in producing the catalysis or substrate inhibition observed with chalcone isomerase. The method presented in this paper allows for the rapid introduction of a series of unnatural amino acids into the active site as a means of probing the structure-function relationship.

E-2-Benzylidenebenzocycloalkanones. IV. Studies on transmission of substituent effects on 13C NMR chemical shifts of E-2-(X-benzylidene)-1-tetralones, and -benzosuberones. Comparison with the 13C NMR data of chalcones and E-2-(X-benzylidene)-1-indanones

NASA Astrophysics Data System (ADS)

Perjési, Pál; Linnanto, Juha; Kolehmainen, Erkki; Ősz, Erzsébet; Virtanen, Elina

2005-04-01

Single substituent parameter (SSP) and dual substituent parameter (DSP) analyses were applied to study the transmission of substituent effects on selected 13C NMR chemical shifts of the cyclic chalcone analogues, E-2-(4'-X-benzylidene)-1-tetralones ( 2) and E-2-(4'-X-benzylidene)-1-benzosuberones ( 3). In order to study how the geometry of the cyclic chalcone analogues affects the transmission of substituent effects similar investigations with the respective chalcones ( 4) were also performed. The results obtained earlier with the five-membered analogue E-2-(4'-X-benzylidene)-1-indanones ( 1) were also involved in the comparisons. Geometry optimization of the unsubstituted 1a, 2a, 3a and 4a as well as the substituted 2 and 3 was performed by ab initio quantum chemical calculations. Both SSP and DSP analyses reflected that resonance effects contribute more to the chemical shift of C-α (C2), while inductive effects primarily affect that of C-β (C10) of the enone moiety of all the four series. This latter effect, however, is far not as pronounced as that of the former one. It was found that DSP analysis data ( ρF and ρR values) of transmission of substituent effects on the δC2 data can serve as a measure of choice to study the conformation (planarity) of the investigated enones in the four series.

Chalcones and their therapeutic targets for the management of diabetes: structural and pharmacological perspectives.

PubMed

Mahapatra, Debarshi Kar; Asati, Vivek; Bharti, Sanjay Kumar

2015-03-06

Diabetes Mellitus (DM) is the fastest growing metabolic disorder affecting about 387 million people across the globe and is estimated to affect 592 million people by year 2030. The search for newer anti-diabetic agents is the foremost need to control the accelerating diabetic population. Several natural and (semi) synthetic chalcones deserve the credit of being potential candidates that act by modulating the therapeutic targets PPAR-γ, DPP-4, α-glucosidase, PTP1B, aldose reductase, and stimulate insulin secretion and tissue sensitivity. In this review, a comprehensive study (from January 1977 to October 2014) of anti-diabetic chalcones, their molecular targets, structure activity relationships (SARs), mechanism of actions (MOAs) and patents have been described. The compounds which showed promising activity and have a well-defined MOAs, SARs must be considered as prototype for the design and development of potential anti-diabetic agents. They should be evaluated critically at all clinical stages to ensure their therapeutic and toxicological profile to meet the demand of diabetics. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Chalcone dendrimer stabilized core-shell nanoparticles—a comparative study on Co@TiO2, Ag@TiO2 and Co@AgCl nanoparticles for antibacterial and antifungal activity

NASA Astrophysics Data System (ADS)

Vanathi Vijayalakshmi, R.; Praveen Kumar, P.; Selvarani, S.; Rajakumar, P.; Ravichandran, K.

2017-10-01

A series of core@shell nanoparticles (Co@TiO2, Ag@TiO2 and Co@AgCl) stabilized with zeroth generation triazolylchalcone dendrimer was synthesized using reduction transmetalation method. The coordination of chalcone dendrimer with silver ions was confirmed by UV-vis spectroscopy. The NMR spectrum ensures the number of protons and carbon signals in the chalcone dendrimer. The prepared samples were structurally characterized by XRD, FESEM and HRTEM analysis. The SAED and XRD analyses exhibited the cubic structure with d hkl   =  2.2 Å, 1.9 Å and 1.38 Å. The antibacterial and antifungal activities of the dendrimer stabilized core@shell nanoparticles (DSCSNPs) were tested against the pathogens Bacillus subtilis, Proteus mirabilis, Candida albicans and Aspergillus nigir from which it is identified that the dendrimer stabilized core shell nanoparticles with silver ions at the shell (Co@AgCl) shows effectively high activity against the tested pathogen following the other core@shell nanoparticles viz Ag@TiO2 and Co@TiO2.

Analysis of the relationship between Chalcone Isomerase gene expression level and rutin production in Ficus deltoidea var. deltoidea and F. deltoidea var. angustifolia

NASA Astrophysics Data System (ADS)

Najid, Najihah Mohd; Zain, Che Radziah Che Mohd; Zainal, Zamri

2016-11-01

Ficus deltoidea (moraceae) is a herbal plant with medicinal values. Previous studies reported that the F. deltoidea contains a high level of bioactive compounds such as flavonoids. A cDNA encodes for chalcone isomerase was identified from F. deltoidea, designated as FdCHI, which involved in the isomerization of naringenin chalcone to naringenin. Naringenin is a key branch point for the synthesis of rutin, which is believed involved in defense mechanism in the plant. Therefore, we hypothesized that there might be a direct relationship between FdCHI expression level and rutin production in leaves of F. deltoidea var. deltoidea (FDD) and F. deltoidea var. angustifolia (FDA). Our result showed that expression level of FdCHI in leaves FDD was greater than FDA. Analysis of High Performance Liquid Chromatography (HPLC) revealed that rutin was only detected in FDA leaves. Based on the results between FdCHI expression and rutin production, this study concluded that there is no relationship between FdCHI expression and rutin production in leaves of FDA and FDD.

Altered sterol profile induced in Leishmania amazonensis by a natural dihydroxymethoxylated chalcone

PubMed Central

Torres-Santos, Eduardo Caio; Sampaio-Santos, Maria Isabel; Buckner, Frederick S.; Yokoyama, Kohei; Gelb, Michael; Urbina, Julio A.; Rossi-Bergmann, Bartira

2009-01-01

Objectives The effects of the antileishmanial chalcone 2′,6′-dihydroxy-4′-methoxychalcone (DMC) on Leishmania amazonensis sterol composition and biosynthesis were investigated to obtain information about the mechanism of growth inhibition by DMC on this parasite. Methods The interference of sterol biosynthesis by DMC was studied in drug-treated promastigotes by two different methods. (i) Newly synthesized sterols from parasites grown in the presence of [3H]mevalonate were analysed by thin layer chromatography (TLC)/fluorography. (ii) Total sterols extracted from the parasites grown with or without DMC were characterized by gas chromatography coupled to mass spectroscopy (GC/MS). Results TLC and GC/MS analyses of sterols extracted from DMC-treated promastigotes revealed the accumulation of early precursors and a reduction in the levels of C-14 demethylated and C-24 alkylated sterols, as well as a reduction in exogenous cholesterol uptake. Conclusions This study demonstrates that the natural chalcone DMC alters the sterol composition of L. amazonensis and suggests that the parasite target is different from other known sterol inhibitors. PMID:19176591

Antibacterial Efficacy of Dihydroxylated Chalcones in Binary and Ternary Combinations with Nalidixic Acid and Nalidix Acid-Rutin Against Escherichia coli ATCC 25 922.

PubMed

Talia, Juan Manuel; Tonn, Carlos Eugenio; Debattista, Nora Beatriz; Pappano, Nora Beatriz

2012-12-01

In order to determine the existence of synergism, the bacteriostatic action of flavonoids against Escherichia coli ATCC 25 922 between dihydroxylated chalcones and a clinically interesting conventional antibiotic, binary combinations of 2',3-dihydroxychalcone, 2',4-dihydroxychalcone and 2',4'-dihydroxychalcone with nalidixic acid and its ternary combinations with rutin (inactive flavonoid) were assayed against this Gram negative bacterium. Using a kinetic-turbidimetric method, growth kinetics were monitored in broths containing variable amounts of dihydroxychalcone alone, combinations of dihydroxychalcone variable concentration-nalidixic acid constant concentration and dihydroxychalcone variable concentration-nalidixic acid constant concentration-rutin constant concentration, respectively. The minimum inhibitory concentrations of dihydroxychalcones alone and its binary and ternary combinations were evaluated. All chalcones, and their binary and ternary combinations showed antibacterial activity, being rutin an excellent synergizing for the dihydroxychalcone-nalidixic acid binary combination against E. coli ATCC 25 922. Thus, this synergistic effect is an important way that could lead to the development of new combination antibiotics against infections caused by E. coli.

Nonlinear optical studies on 1,3-disubstituent chalcones doped polymer films

NASA Astrophysics Data System (ADS)

Poornesh, P.; Shettigar, Seetharam; Umesh, G.; Manjunatha, K. B.; Prakash Kamath, K.; Sarojini, B. K.; Narayana, B.

2009-04-01

We report the measurements of the third-order nonlinear optical properties of recently synthesized and characterized two different 1,3-disubstituent chalcones doped PMMA films, with the prospective of reaching a good compromise between processability and high nonlinear optical properties. The measurements were done using nanosecond Z-scan at 532 nm. The Z-scan spectra reveal a large negative nonlinear refraction coefficient n2 of the order 10 -11 esu and the molecular two photon absorption cross section is 10 -46 cm 4 s/photon. The doped films exhibit good optical power limiting property under nanosecond regime and the two photon absorption (TPA) is the dominating process leading to the nonlinear behavior. The improvement in the nonlinear properties has been observed when methylenedioxy group is replaced by dimethoxy group due to increase in conjugation length. The observed nonlinear parameters of chalcone derivatives doped PMMA film is comparable with stilbazolieum derivatives, a well-known class of optical materials for photonics and biophotonics applications, which suggests that, these moieties have potential for the application of all-optical limiting and switching devices.

Derricin and Derricidin Inhibit Wnt/β-Catenin Signaling and Suppress Colon Cancer Cell Growth In Vitro

PubMed Central

Fonseca, Barbara F.; Predes, Danilo; Cerqueira, Debora M.; Reis, Alice H.; Amado, Nathalia G.; Cayres, Marina C. L.; Kuster, Ricardo M.; Oliveira, Felipe L.; Mendes, Fabio A.; Abreu, Jose G.

2015-01-01

Overactivation of the Wnt/β-catenin pathway in adult tissues has been implicated in many diseases, such as colorectal cancer. Finding chemical substances that can prevent this phenomenon is an emerging problem. Recently, several natural compounds have been described as Wnt/β-catenin inhibitors and might be promising agents for the control of carcinogenesis. Here, we describe two natural substances, derricin and derricidin, belonging to the chalcone subclass, that show potent transcriptional inhibition of the Wnt/β-catenin pathway. Both chalcones are able to affect the cell distribution of β-catenin, and inhibit Wnt-specific reporter activity in HCT116 cells and in Xenopus embryos. Derricin and derricidin also strongly inhibited canonical Wnt activity in vitro, and rescued the Wnt-induced double axis phenotype in Xenopus embryos. As a consequence of Wnt/β-catenin inhibition, derricin and derricidin treatments reduce cell viability and lead to cell cycle arrest in colorectal cancer cell lines. Taken together, our results strongly support these chalcones as novel negative modulators of the Wnt/β-catenin pathway and colon cancer cell growth in vitro. PMID:25775405

Ultrasound accelerated Claisen Schmidt condensation: A green route to chalcones

NASA Astrophysics Data System (ADS)

Calvino, V.; Picallo, M.; López-Peinado, A. J.; Martín-Aranda, R. M.; Durán-Valle, C. J.

2006-06-01

Chalcones have been synthesized under sonochemical irradiation by Claisen-Schmidt condensation between benzaldehyde and acetophenone. Two basic activated carbons (Na and Cs-Norit) have been used as catalysts. The effect of the ultrasound activation has been studied. A substantial enhancing effect in the yield was observed when the carbon catalyst was activated under ultrasonic waves. This "green" method (combination of alkaline-doped carbon catalyst and ultrasound waves) has been applied to the synthesis of several chalcones with antibacterial properties achieving, in all cases, excellent activities and selectivities. A comparative study under non-sonic activation has showed that the yields are lower in silent conditions, indicating that the sonication exerts a positive effect on the activity of the catalyst. Cs-doped carbon is presented as the optimum catalyst, giving excellent activity for this type of condensation. Cs-Norit carbon catalyst can compete with the traditional NaOH/EtOH when the reaction is carried out under ultrasounds. The role of solvent in this reaction was studied with ethanol. High conversion was obtained in absence of solvent. The carbons were characterized by thermal analysis, nitrogen adsorption and X-ray photoelectron spectroscopy.

The chalcone 2'-hydroxy-4',5'-dimethoxychalcone activates death receptor 5 pathway and leads to apoptosis in human nonsmall cell lung cancer cells.

PubMed

Yang, Lina; Su, Ling; Cao, Congmei; Xu, Linyan; Zhong, Diansheng; Xu, Lijia; Liu, Xiangguo

2013-06-01

Natural chalcones have been proved to inhibit cancer cells with therapeutic potential, but the underlying molecular mechanism is still largely unexplored. Here, we identified a novel chalcone, 2'-hydroxy-4',5'-dimethoxychalcone (HDMC) and demonstrated that HDMC induced apoptosis in various nonsmall cell lung cancer cells. Further study showed that HDMC elevated cellular reactive oxygen species (ROS) levels, thus inducing expressions of ATF4 and C/EBP homologous protein (CHOP). Then, death receptor 5 (DR5) was upregulated through ATF4-CHOP axis and eventually resulted in apoptosis. We also found that downregulation of c-FLIPL contributed to HDMC-induced apoptosis. In conclusion, HDMC induces apoptosis in human nonsmall cell lung cancer cells via activation of DR5 signaling pathway, and ROS-mediated ATF4-CHOP axis is involved in the process. Our results further supported the potential for HDMC to be developed as a new antitumor agent for cancer therapy or chemoprevention. Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.

Biotransformation of Flavokawains A, B, and C, Chalcones from Kava (Piper methysticum), by Human Liver Microsomes.

PubMed

Zenger, Katharina; Agnolet, Sara; Schneider, Bernd; Kraus, Birgit

2015-07-22

The in vitro metabolism of flavokawains A, B, and C (FKA, FKB, FKC), methoxylated chalcones from Piper methysticum, was examined using human liver microsomes. Phase I metabolism and phase II metabolism (glucuronidation) as well as combined phase I+II metabolism were studied. For identification and structure elucidation of microsomal metabolites, LC-HRESIMS and NMR techniques were applied. Major phase I metabolites were generated by demethylation in position C-4 or C-4' and hydroxylation predominantly in position C-4, yielding FKC as phase I metabolite of FKA and FKB, helichrysetin as metabolite of FKA and FKC, and cardamonin as metabolite of FKC. To an even greater extent, flavokawains were metabolized in the presence of uridine diphosphate (UDP) glucuronic acid by microsomal UDP-glucuronosyl transferases. For all flavokawains, monoglucuronides (FKA-2'-O-glucuronide, FKB-2'-O-glucuronide, FKC-2'-O-glucuronide, FKC-4-O-glucuronide) were found as major phase II metabolites. The dominance of generated glucuronides suggests a role of conjugated chalcones as potential active compounds in vivo.

Synthesis of mono Mannich bases of 2-(4-hydroxybenzylidene)-2,3-dihydroinden-1-one and evaluation of their cytotoxicities.

PubMed

Tugrak, Mehtap; Yamali, Cem; Sakagami, Hiroshi; Gul, Halise Inci

2016-10-01

Chalcones and Mannich bases are a group of compounds known for their cytotoxicities. In this study restricted chalcone analogue, compound 2-(4-hydroxybenzylidene)-2,3-dihydroinden-1-one MT1, was used as a starting compound to synthesize new mono Mannich bases since Mannich bases may induce more cytotoxicity than chalcone analogue that they are derived from by producing additional alkylating center for cellular thiols. In this study, cyclic and acyclic amines were used to synthesize Mannich bases. All compounds were tested against Ca9-22 (gingival carcinoma), HSC-2, HSC-3 and HSC-4 (oral squamous cell carcinoma) as tumour cell lines and HGF (gingival fibroblasts), HPC (pulp cells) and HPLF (periodontal ligament fibroblasts) human normal oral cells as non tumour cell lines. Cytotoxicity, selectivity index (SI) values and potency selectivity expression (PSE) values expressed as a percentage were determined for the compounds. According to data obtained, the compound MT8 with the highest PSE value bearing N-methylpiperazine moiety seems to be a good candidate to develop new cytotoxic compounds and is suited for further investigation.

The synthesis of 2-(5-(3-methoxyphenyl)-4,5-dihydro-1H-pyrazol-3-yl)phenol using sodium impregnated on activated chicken eggshells catalyst

NASA Astrophysics Data System (ADS)

Mardiana, L.; Bakri, R.; Septiarti, A.; Ardiansah, B.

2017-04-01

The novel compound of 2-(5-(3-methoxyphenyl)-4,5-dihydro-1H-pyrazol-3-yl)phenol as a pyrazoline derivative has been synthesized by two-steps reaction using sodium impregnated on activated chicken eggshells (Na-ACE) catalyst. Na-ACE was primarily prepared by a simple wet impregnation of NaOH solution on activated chicken eggshells solid support. The Na-ACE catalyst produced was characterized using FTIR spectrophotometer, XRD and SEM then applied in pyrazoline synthesis. First, chalcone was prepared from the reaction of 2-hydroxyacetophenone and 3-methoxybenzaldehyde by base-catalyzed aldol condensation. This product was subsequently reacted with hydrazine hydrate to give corresponding pyrazoline. The structure elucidation of the compound using FTIR, UV-Vis, LC-ESI-MS and 1H-NMR indicated the desired product has been successfully synthesized. Furthermore, the potential antioxidant activities of chalcone and pyrazoline have also been studied in-vitro using DPPH radical scavenging method. The results revealed that pyrazoline has a greater antioxidant activity than chalcone.

Identification and characterisation of DfCHS, a chalcone synthase gene regulated by temperature and ultraviolet in Dryopteris fragrans.

PubMed

Sun, L L; Li, Y; Li, S S; Wu, X J; Hu, B Z; Chang, Y

2014-12-30

Chalcone synthase (CHS) is an enzyme that catalyzes the first committed step in flavonoid biosynthesis, and its transcription level is regulated by light conditions. By using homology cloning and rapid amplification of cDNA ends, we cloned a chalcone synthase gene (DfCHS) from Dryopteris fragrans (L.) Schott. The full-length cDNA of DfCHS is 1,737 bp, with an open reading frame (ORF) of 1,122 bp (deposited in GenBank under Accession Number KF530802) encoding a predicted protein of 373 amino acids. The calculated molecular mass of DfCHS is 41.3 kDa. We studied the expression of DfCHS and total flavonoid contents in tissue culture seedlings cultured under the low temperature at 4ºC, high temperature at 35ºC and UV conditions, respectively. The results show that the expression of DfCHS are not the same, but all present rising trends, then flavonoid contents were increased. Overall, our results imply that the expression of DfCHS gene provide a certain theory basis in the status of evolution among ferns.

Synthesis and structure-activity relationship studies of furan-ring fused chalcones as antiproliferative agents.

PubMed

Saito, Yusuke; Kishimoto, Maho; Yoshizawa, Yuko; Kawaii, Satoru

2015-02-01

As part of our continuing investigation of flavonoid derivatives as potential anticancer substances, the synthesis of 25 cinnamoyl derivatives of benzofuran as furan-fused chalcones was carried-out and these compounds were further evaluated for their antiproliferative activity towards HL60 promyelocytic leukemia cells. In comparison with 2',4'-dihydroxychalcone, attachment of a furan moiety on the A-ring enhanced activity by more than twofold. Benzofurans may be useful in the design of biologically active flavonoids. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

[Chalcones from Bauhinia glauca subsp. pernervosa].

PubMed

Wu, Zengbao; Wang, Bin; Zhao, Yuying; Yang, Xiuwei; Liang, Hong

2009-07-01

To study the chemical constituents of Bauhinia glauca subsp. pernervosa. The coulis of B. glauca subsp. pernervosa were extracted with 95% EtOH at room temperature. The compounds were isolated and separated by chromatographic techniques, and structures were identified by spectroscopic methods. Seven chalcones were isolated and identified: butein-4-methyl ether (1), isoliquiritigenin (2), butein (3), isoliquiritigenin-2'-methyl ether (4), 2',4'-dihydroxychalcone (5), isoliquiritigenin-4-methyl ether (6), 4-hydroxy-2',4'-dimethoxychalcone (7). Compounds 1, 3, and 7 were isolated from the genus Bauhinia for the first time, the other compounds were obtained from this plant for the first time.

Chalcones and other constituents of Dorstenia prorepens and Dorstenia zenkeri.

PubMed

Abegaz, Berhanu M; Ngadjui, Bonaventure T; Dongo, Etienne; Ngameni, Bathelemy; Nindi, Mathew N; Bezabih, Merhatibeb

2002-04-01

The twigs of Dorstenia prorepens furnished the digeranylated chalcone, 5,3'-(3,7-dimethyl-2,6-octadienyl)-3,4, 2',4'-tetrahydroxychalcone while Dorstenia zenkeri yielded the 3',4'-(3-hydroxy-2,2-dimethyldihydropyrano)-4,2'-dihydroxychalcone and a bichalcone. 4-Hydroxylonchocarpin was found in both plants. D. prorepens also yielded the known compounds: psoralen, bergapten, beta-sitosterol and its D-glucopyranosyl derivative. D. zenkeri yielded p-hydroxybenzaldehyde, dorsmanin A, 4,2',4'-trihydroxychalcone and 4,2',4'-trihydroxy-3'-prenylchalcone. Structures of the new compounds were established by UV, IR, MS and 2-D NMR analysis.

Derivatives of Δ 2-pyrazoline-products of 1,5-diaminotetrazole interaction with chalcone: Molecular structure and spectral properties

NASA Astrophysics Data System (ADS)

Kolos, N. N.; Paponov, B. V.; Orlov, V. D.; Lvovskaya, M. I.; Doroshenko, A. O.; Shishkin, O. V.

2006-03-01

1,5-diaminotetrazole at conditions of its interaction with chalcones (1,3-diphenylpropenones) in hot DMF undergoes Dimroth rearrangement to 5-tetrazolylhydrazine, which results in formation of 1-(5-tetrazolyl)-3,5-diaryl-Δ 2-pyrazolines ( I). Structure of the obtained products was confirmed by their parallel synthesis and X-ray structural analysis. Unusual fluorescence behavior of the tetrazolopyrazolynes in polar solvents was attributed to the dissociation of their highly acidic tetrazole N-H group. The last hypothesis was confirmed at the investigation of the protolytic interactions of I with tertiary amine.

Supramolecular architectures constructed through self-assembly of a chalcone and substituted diazo-β-diketones

NASA Astrophysics Data System (ADS)

Prajapati, R.; Mishra, L.; Grabowski, S. J.; Govil, G.; Dubey, S. K.

2008-05-01

Organic compounds namely pyridyl chalcone viz. 3-[4-(3-oxo-3-pyridin-2-yl-propenyl)-phenyl]-1-pyridin-2-yl-propenone (L 1), p-cholorophenyldiazopentane-2,4-dione (L 2) and p-methyl phenyldiazopentane-2,4-dione (L 3) have been characterized by their single-crystal X-ray crystallographic studies. Several structural motifs resulting upon their self-association through probable non-covalent interactions have been discussed. The studies of related motifs found in Cambridge Structural Database are performed and the results are related to the structural data obtained for crystal structures reported here in.

Nanoemulsions containing a synthetic chalcone as an alternative for treating cutaneous leshmaniasis: optimization using a full factorial design

PubMed Central

de Mattos, Cristiane Bastos; Argenta, Débora Fretes; Melchiades, Gabriela de Lima; Sechini Cordeiro, Marlon Norberto; Tonini, Maiko Luis; Moraes, Milene Hoehr; Weber, Tanara Beatriz; Roman, Silvane Souza; Nunes, Ricardo José; Teixeira, Helder Ferreira; Steindel, Mário; Koester, Letícia Scherer

2015-01-01

Nanoemulsions are drug delivery systems that may increase the penetration of lipophilic compounds through the skin, enhancing their topical effect. Chalcones are compounds of low water solubility that have been described as promising molecules for the treatment of cutaneous leishmaniasis (CL). In this context, the aim of this work was to optimize the development of a nanoemulsion containing a synthetic chalcone for CL treatment using a 22 full factorial design. The formulations were prepared by spontaneous emulsification and the experimental design studied the influence of two independent variables (type of surfactant – soybean lecithin or sorbitan monooleate and type of co-surfactants – polysorbate 20 or polysorbate 80) on the physicochemical characteristics of the nanoemulsions, as well as on the skin permeation/retention of the synthetic chalcone in porcine skin. In order to evaluate the stability of the systems, the antileishmanial assay was performed against Leishmania amazonensis 24 hours and 60 days after the preparation of the nanoemulsions. The formulation composed of soybean lecithin and polysorbate 20 presented suitable physicochemical characteristics (droplet size 171.9 nm; polydispersity index 0.14; zeta potential −39.43 mV; pH 5.16; and viscosity 2.00 cP), drug content (91.09%) and the highest retention in dermis (3.03 µg·g−1) – the main response of interest – confirmed by confocal microscopy. This formulation also presented better stability of leishmanicidal activity in vitro against L. amazonensis amastigote forms (half maximal inhibitory concentration value 0.32±0.05 µM), which confirmed the potential of the nanoemulsion soybean lecithin and polysorbate 20 for CL treatment. PMID:26366075

A new brominated chalcone derivative suppresses the growth of gastric cancer cells in vitro and in vivo involving ROS mediated up-regulation of DR5 and 4 expression and apoptosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Saiyang; Li, Tingyu; Zhang, Yanbing

A new series of 20 brominated chalcone derivatives were designed, synthesized, and investigated for their effects against the growth of four cancer cell lines (EC109, SKNSH, HepG2, MGC803). Among them, compound 19 which given chemical name of H72, was the most potent one on gastric cancer cell lines (i.e. MGC803, HGC27, SGC7901) with IC{sub 50s} ranged from 3.57 to 5.61 μM. H72 exhibited less cytotoxicity to non-malignant gastric epithelial cells GES-1. H72 treatment of MGC803 and HGC27 induced generation of reactive oxygen species (ROS) leading to activation of caspase 9/3 cascade and mitochondria mediated apoptosis. H72 also up-regulated the expressionmore » of DR5, DR4 and Bim{sub EL}, and down-regulated the expression of Bid, Bcl-xL, and XIAP. N-acetyl cysteine (NAC), a ROS scavenger completely blocked these effects of H72 in MGC803 cells. Intraperitoneal administration of H72 significantly inhibited the growth of MGC803 cells in vivo in a xenograft mouse model without observed toxicity. These results indicated that H72 is a lead brominated chalcone derivate and deserves further investigation for prevention and treatment of gastric cancer. - Highlights: • 20 brominated chalcone derivatives were designed and synthesized. • H72 caused potent cytotoxic activity against MGC803 and less against GES1. • H72 led to activation of caspase 9/3 cascade and mitochondria mediated apoptosis. • H72 induced generation of reactive oxygen species (ROS). • H72 significantly inhibited the growth of MGC803 cells in vivo.« less

4'-Acetoamido-4-hydroxychalcone, a chalcone derivative, inhibits glioma growth and invasion through regulation of the tropomyosin 1 gene

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ku, Bo Mi; Ryu, Hyung Won; Lee, Yeon Kyung

2010-11-19

Research highlights: {yields} 4'-Acetoamido-4-hydroxychalcone (AHC) has anti-cancer property for glioma. {yields} 4'-Acetoamido-4-hydroxychalcone (AHC) increased tropomyosin expreesion through activattion of PKA signaling. {yields} 4'-Acetoamido-4-hydroxychalcone (AHC) inhibits glioma cell migration and invasion. {yields} In vivo administration of 4'-acetoamido-4-hydroxychalcone (AHC) reduced tumor growth. -- Abstract: Chalcones are precursors of flavonoids and have been shown to have anti-cancer activity. Here, we identify the synthetic chalcone derivative 4'-acetoamido-4-hydroxychalcone (AHC) as a potential therapeutic agent for the treatment of glioma. Treatment with AHC reduced glioma cell invasion, migration, and colony formation in a concentration-dependent manner. In addition, AHC inhibited vascular endothelial growth factor-induced migration, invasion, andmore » tube formation in HUVECs. To determine the mechanism underlying the inhibitory effect of AHC on glioma cell invasion and migration, we investigated the effect of AHC on the gene expression change and found that AHC affects actin dynamics in U87MG glioma cells. In actin cytoskeleton regulating system, AHC increased tropomyosin expression and stress fiber formation, probably through activation of PKA. Suppression of tropomyosin expression by siRNA or treatment with the PKA inhibitor H89 reduced the inhibitory effects of AHC on glioma cell invasion and migration. In vivo experiments also showed that AHC inhibited tumor growth in a xenograft mouse tumor model. Together, these data suggest that the synthetic chalcone derivative AHC has potent anti-cancer activity through inhibition of glioma proliferation, invasion, and angiogenesis and is therefore a potential chemotherapeutic candidate for the treatment of glioma.« less

Synthetic Chalcones with Potent Antioxidant Ability on H2O2-Induced Apoptosis in PC12 Cells

PubMed Central

Wu, Jian-Zhang; Cheng, Chan-Chan; Shen, Lai-Lai; Wang, Zhan-Kun; Wu, Shou-Biao; Li, Wu-Lan; Chen, Su-Hua; Zhou, Rong-Ping; Qiu, Pei-Hong

2014-01-01

Chalcone derivatives (E)-3-(4-hydroxy-3-methoxyphenyl)-1-(4-methoxyphenyl) prop-2-en-1-one and (E)-3-(4-hydroxyphenyl)-1-(4-methoxyphenyl) prop-2-en-1-one (Compounds 1 and 2) have been demonstrated to be potent anti-inflammatory agents in our previous study. In light of the relationship of intracellular mechanisms between anti-inflammatories and antioxidants, we further designed and synthesized a series of chalcone derivatives based on 1 and 2, to explore their antioxidant efficacy. The majority of the derivatives exhibited strong protective effects on PC12 (PC12 rat pheochromocytoma) cells exposed to H2O2, and all compounds were nontoxic. A preliminary structure-activity relationship was proposed. Compounds 1 and 1d ((E)-2-methoxy-4-(3-(4-methoxyphenyl)-3-oxoprop-1-en-1-yl) phenyl acrylate) exerted the action in a good dose-dependent manner. Quantitative RT-PCR (qRT-PCR) and western blot analysis showed that 1 and 1d significantly improve the expression of nuclear factor erythroid 2 p45-related factor 2 (Nrf2)-dependent antioxidant genes g-Glutamylcysteine Ligase Catalytic Subunit (GCLC) and heme oxygenase-1 (HO-1) and their corresponding proteins (γ-glutamyl cysteine synthase (γ-GCS) and HO-1) in PC12 cells. Inhibition of GCLC and HO-1 by specific inhibitors, l-buthionine-S-sulfoximine (BSO) and zinc protoporphyrin (ZnPP), respectively, partially reduce the protective effect of 1 and 1d. These data present a series of novel chalcone analogs, especially compounds 1 and 1d, as candidates for treating oxidative stress-related disease by activating the Nrf2-antioxidant responsive element (ARE) pathway. PMID:25318055

Nanoemulsions containing a synthetic chalcone as an alternative for treating cutaneous leshmaniasis: optimization using a full factorial design.

PubMed

de Mattos, Cristiane Bastos; Argenta, Débora Fretes; Melchiades, Gabriela de Lima; Cordeiro, Marlon Norberto Sechini; Tonini, Maiko Luis; Moraes, Milene Hoehr; Weber, Tanara Beatriz; Roman, Silvane Souza; Nunes, Ricardo José; Teixeira, Helder Ferreira; Steindel, Mário; Koester, Letícia Scherer

2015-01-01

Nanoemulsions are drug delivery systems that may increase the penetration of lipophilic compounds through the skin, enhancing their topical effect. Chalcones are compounds of low water solubility that have been described as promising molecules for the treatment of cutaneous leishmaniasis (CL). In this context, the aim of this work was to optimize the development of a nanoemulsion containing a synthetic chalcone for CL treatment using a 2(2) full factorial design. The formulations were prepared by spontaneous emulsification and the experimental design studied the influence of two independent variables (type of surfactant - soybean lecithin or sorbitan monooleate and type of co-surfactants - polysorbate 20 or polysorbate 80) on the physicochemical characteristics of the nanoemulsions, as well as on the skin permeation/retention of the synthetic chalcone in porcine skin. In order to evaluate the stability of the systems, the antileishmanial assay was performed against Leishmania amazonensis 24 hours and 60 days after the preparation of the nanoemulsions. The formulation composed of soybean lecithin and polysorbate 20 presented suitable physicochemical characteristics (droplet size 171.9 nm; polydispersity index 0.14; zeta potential -39.43 mV; pH 5.16; and viscosity 2.00 cP), drug content (91.09%) and the highest retention in dermis (3.03 µg·g(-1)) - the main response of interest - confirmed by confocal microscopy. This formulation also presented better stability of leishmanicidal activity in vitro against L. amazonensis amastigote forms (half maximal inhibitory concentration value 0.32±0.05 µM), which confirmed the potential of the nanoemulsion soybean lecithin and polysorbate 20 for CL treatment.

In vitro and in vivo anti-glioma activity of a chalcone-quinoxaline hybrid.

PubMed

Loch-Neckel, Gecioni; Bicca, Maíra Assunção; Leal, Paulo César; Mascarello, Alessandra; Siqueira, Jarbas Mota; Calixto, João B

2015-01-27

Chalcones are important compounds that exhibit multiple biological activities, including anti-inflammatory, antimitotic and antibacterial properties. In the present study, we have analyzed the potential anti-cancer activity of a chalcone named N9 (a hybrid chalcone-quinoxaline compound) using in vitro and in vivo experimental glioma models. Here, we report N9-induced inhibition of cell proliferation and also N9-induced cell death in a concentration-dependent manner in U87-MG glioma cells. These effects of N9 appear to be associated with its ability to inhibit the expression of cell cycle-associated proteins, and also the augmentation in the expression of the p21 (p21/Cip1) protein, a cyclin-dependent kinase inhibitor. Additionally, N9 also potentiates the production of the pro-apoptotic markers Bax and p53 via inhibition of MDM2. Moreover, our results show that N9 also significantly enhanced apoptosis of U87-MG cells with disruption of mitochondrial membrane potential, generation of ROS and caspase-9 activation. In vivo experiments carried out in a murine xenograft model of U87-MG revealed that N9 produced a significant reduction of tumors volume when compared to vehicle treated mice. Collectively, data demonstrate that N9 possess in vitro and in vivo anti-cancer activity, an effect that seems to involve the induction of p53 and p21 proteins, as well as, the activation of mitochondrial apoptosis pathway associated with the inhibition of protein MDM2. Overall, this study suggests N9 is affecting a variety of intracellular pathways related to tumor apoptosis. Perhaps N9 or derivate molecules could represent new potential drugs for cancer therapeutics. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Genotoxic, Cytotoxic, Antigenotoxic, and Anticytotoxic Effects of Sulfonamide Chalcone Using the Ames Test and the Mouse Bone Marrow Micronucleus Test

PubMed Central

Borges, Flávio Fernandes Veloso; Bernardes, Aline; Perez, Caridad Noda; Silva, Daniela de Melo e

2015-01-01

Chalcones present several biological activities and sulfonamide chalcone derivatives have shown important biological applications, including antitumor activity. In this study, genotoxic, cytotoxic, antigenotoxic, and anticytotoxic activities of the sulfonamide chalcone N-{4-[3-(4-nitrophenyl)prop-2-enoyl]phenyl} benzenesulfonamide (CPN) were assessed using the Salmonella typhimurium reverse mutation test (Ames test) and the mouse bone marrow micronucleus test. The results showed that CPN caused a small increase in the number of histidine revertant colonies in S. typhimurium strains TA98 and TA100, but not statistically significant (p > 0.05). The antimutagenicity test showed that CPN significantly decreased the number of His+ revertants in strain TA98 at all doses tested (p < 0.05), whereas in strain TA100 this occurred only at doses higher than 50 μg/plate (p < 0.05). The results of the micronucleus test indicated that CPN significantly increased the frequency of micronucleated polychromatic erythrocytes (MNPCE) at 24 h and 48 h, revealing a genotoxic effect of this compound. Also, a significant decrease in polychromatic/normochromatic erythrocyte ratio (PCE/NCE) was observed at the higher doses of CPN at 24 h and 48 h (p < 0.05), indicating its cytotoxic action. CPN co-administered with mitomycin C (MMC) significantly decreased the frequency of MNPCE at almost all doses tested at 24 h (p < 0.05), showing its antigenotoxic activity, and also presented a small decrease in MNPCE at 48 h (p > 0.05). Additionally, CPN co-administered with MMC significantly increased PCE/NCE ratio at all doses tested, demonstrating its anticytotoxic effect. In summary, CPN presented genotoxic, cytotoxic, antigenotoxic, and anticytotoxic properties. PMID:26335560

Synthesis and Cytotoxic Activities of Difluoro-Dimethoxy Chalcones.

PubMed

Yamali, Cem; Gul, Halise Inci; Ozgun, Dilan Ozmen; Sakagam, Hiroshi; Umemura, Naoki; Kazaz, Cavit; Gul, Mustafa

2017-01-01

Although anticancer chemotherapeutics are available in markets, side effects related to the drugs in clinical use lead to researchers to investigate new drug candidates which are more safe, potent and selective than others. Chalcones are popular with their anticancer activities with the several reported mechanisms including inhibition of angiogenesis, inhibition of tubulin polymerization, and induction of apoptosis etc. This study was focused on to synthesize of 1-(2,4/2,6-difluorophenyl)-3-(2,3/2,4/2,5/3,4- dimethoxyphenyl)-2-propen-1-ones (1-8) and investigate their cytotoxic properties with possible mechanism of action. The compounds were synthesized by Claisen-Schmidt condensation. The chemical structures were confirmed by 1H NMR, 13C NMR, DEPT, COSY, HMQC, HMBC, 19F NMR and HRMS. In vitro cytotoxic effects of the compounds against human tumour cell lines [gingival carcinoma (Ca9-22), oral squamous cell carcinoma (HSC-2)] and human normal oral cells [gingival fibroblasts (HGF), periodontal ligament fibroblasts (HPLF)] were evaluated via MTT test. All compounds had higher cytotoxicity than reference compound 5-Fluorouracil (5-FU). The compounds 3-7 had higher potency selectivity expression values (PSE) than 5-FU and PSE values of the compounds were over 100. All chalcone derivatives seem good candidates for further studies according to very remarkable and high PSE values. It was clearly demonstrated that compound 7 can induce early apoptosis at a concentration of 10 µM and dose-dependent late apoptosis starting at 10 µM. Compound 7 induced cleavage of the apoptosis marker PARP. The results indicate that new chalcones reported here can promote apoptosis in human tumour cell lines. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Meroterpenoids and Chalcone-Lignoids from the Roots of Mimosa diplotricha.

PubMed

Chiou, Chun-Tang; Shen, Chien-Chang; Tsai, Tung-Hu; Chen, Yu-Jen; Lin, Lie-Chwen

2016-10-28

Six new meroterpenoids, diplomeroterpenoids A-F (1-6), two new chalcone-lignoids, diplochalcolins A and B (7, 8), and 13 known compounds were isolated from the root extract of Mimosa diplotricha. Diplomeroterpenoids A-F consist of a 4H-chromen-4-one and a diterpenoid unit, and their absolute configurations were determined by X-ray crystallographic analysis. Compounds 1-3 and 5 showed potent inhibitory activity on protein farnesyl transferase, with IC 50 values from 5.0 to 8.5 μM. Compound 1 showed antiproliferative activity against human hepatoblastoma HepG2 cells with a GI 50 value of approximately 8.6 μM.

Anticarcinogenic compounds in the Uzbek medicinal plant, Helichrysum maracandicum.

PubMed

Yagura, Toru; Motomiya, Tomoko; Ito, Michiho; Honda, Gisho; Iida, Akira; Kiuchi, Fumiyuki; Tokuda, Harukuni; Nishino, Hoyoku

2008-04-01

An ethanol extract of Helichrysum maracandicum showed antiproliferative activity against cultured cells of SENCAR mouse in an in vitro assay, and activity-guided fractionation of the extract resulted in the isolation of isosalipurposide as an active substance. Naringenin chalcone, the aglycone of isosalipurposide, also showed strong antiproliferative activity. An in vivo assay of two-stage carcinogenesis on mouse skin revealed that epidermal application of isosalipurposide resulted in delayed formation of papillomas. Western blot analysis showed that the expression of p38 mitogen-activated protein kinase was suppressed by the administration of naringenin chalcone or isosalipurposide, which might be related to the anticarcinogenic activity.

Chalcone dimethylallyltransferase from Morus nigra cell cultures. Substrate specificity studies.

PubMed

Vitali, Alberto; Giardina, Bruno; Delle Monache, Giuliano; Rocca, Filippo; Silvestrini, Andrea; Tafi, Andrea; Botta, Bruno

2004-01-16

A new prenyltransferase (PT) enzyme derived from the microsomal fractions of cell cultures of Morus nigra was shown to be able to prenylate exclusively chalcones with a 2',4'-dihydroxy substitution and the isoflavone genistein. Computational studies were performed to shed some light on the relationship between the structure of the substrate and the enzymatic activity. PT requires divalent cations, particularly Mg(2+), to be effective. The apparent K(m) values for gamma,gamma-dimethylallyldiphosphate and 2',4'-dihydroxychalcone were 63 and 142 microM, respectively. The maximum activity of the enzyme was expressed during the first 10 days of cell growth.

Organobase catalyzed 1,4-conjugate addition of 4-hydroxycoumarin on chalcones: Synthesis, NMR and single-crystal X-ray diffraction studies of novel warfarin analogues

NASA Astrophysics Data System (ADS)

Talhi, Oualid; Fernandes, José A.; Pinto, Diana C. G. A.; Almeida Paz, Filipe A.; Silva, Artur M. S.

2015-08-01

The synthesis of a new series of warfarin analogues by convenient organobase catalyzed 1,4-conjugate addition of 4-hydroxycoumarin to chalcone derivatives is described. 1H NMR spectroscopy evidenced the presence of a predominant acyclic open-form together with the cyclic hemiketal tautomers of the resulting Michael adducts. The acyclic open-form has been unequivocally proved by single-crystal X-ray diffraction analysis. The use of the B ring ortho-hydroxychalcone synthons in this reaction has led to a diastereoselective synthesis of warfarin bicyclo[3.3.1]nonane ketal derivatives.

Multiple biological activities and molecular docking studies of newly synthesized 3-(pyridin-4-yl)-1H-pyrazole-5-carboxamide chalcone hybrids.

PubMed

Sribalan, Rajendran; Banuppriya, Govindharasu; Kirubavathi, Maruthan; Jayachitra, A; Padmini, Vediappen

2016-12-01

A series of fifteen new chemical entities, 3-(pyridin-4-yl)-1H-pyrazole-5-carboxamide chalcones (6a-o), were synthesized as new hybrids with enriched biological activities compared to their parent molecules. The compounds were characterized by 1 H NMR, 13 C NMR, Mass and IR spectral studies. Their antibacterial, anti-inflammatory and antioxidant activities have been evaluated. These compounds showed moderate to good antibacterial, anti-inflammatory and antioxidant activities. The molecular docking analysis was performed with cyclooxygenase enzyme to ascertain the probable binding model. Copyright © 2016 Elsevier Ltd. All rights reserved.

Features of the reaction of heterocyclic analogs of chalcone with lanthanide shift reagents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Turov, A.V.; Khilya, V.P.

1994-10-01

The PMR spectra of heterocyclic analogs of 2-hydroxychalcone containing thiazole, benzofuran, triazole, imidazole, benzodioxane, or pyridine rings in the presence of lanthanide shift reagents are studied. It is found that the most effective reagent for modifying the spectra of these compounds is Yb(fod)3. The broadening of the spectra of 2-hydroxy chalcones in the presence of lanthanide shift reagents is explained by the dynamic effects of complex formation. An example is given of the determination of the conformation of molecules of 2-hydroxychalcone by the simultaneous use of lanthanide shift reagents and the homonuclear Overhauser effect. 9 refs., 1 fig., 1 tab.

Synthetic cyclohexenyl chalcone natural products possess cytotoxic activities against prostate cancer cells and inhibit cysteine cathepsins in vitro.

PubMed

Deb Majumdar, Ishita; Devanabanda, Arvind; Fox, Benjamin; Schwartzman, Jacob; Cong, Huan; Porco, John A; Weber, Horst C

2011-12-16

A number of cyclohexenyl chalcone Diels-Alder natural products possess promising biological properties including strong cytotoxicity in various human cancer cells. Herein, we show that natural products in this class including panduratin A and nicolaioidesin C inhibit cysteine cathepsins as indicated by protease profiling assays and cell-free cathepsin L enzyme assays. Owing to the critical roles of cathepsins in the biology of human tumor progression, invasion, and metastasis, these findings should pave the way for development of novel antitumor agents for use in clinical settings. Copyright © 2011 Elsevier Inc. All rights reserved.

Anticarcinogenic Effect of Spices Due to Phenolic and Flavonoid Compounds-In Vitro Evaluation on Prostate Cells.

PubMed

Lackova, Zuzana; Buchtelova, Hana; Buchtova, Zaneta; Klejdus, Borivoj; Heger, Zbynek; Brtnicky, Martin; Kynicky, Jindrich; Zitka, Ondrej; Adam, Vojtech

2017-09-28

This study shows the effects of spices, and their phenolic and flavonoid compounds, on prostate cell lines (PNT1A, 22RV1 and PC3). The results of an MTT assay on extracts from eight spices revealed the strongest inhibitory effects were from black pepper and caraway seed extracts. The strongest inhibitory effect on prostatic cells was observed after the application of extracts of spices in concentration of 12.5 mg·mL -1 . An LC/MS analysis identified that the most abundant phenolic and flavonoid compounds in black pepper are 3,4-dihydroxybenzaldehyde and naringenin chalcone, while the most abundant phenolic and flavonoid compounds in caraway seeds are neochlorogenic acid and apigenin. Using an MTT assay for the phenolic and flavonoid compounds from spices, we identified the IC 50 value of ~1 mmol·L -1 PNT1A. The scratch test demonstrated that the most potent inhibitory effect on PNT1A, 22RV1 and PC3 cells is from the naringenin chalcone contained in black pepper. From the spectrum of compounds assessed, the naringenin chalcone contained in black pepper was identified as the most potent inhibitor of the growth of prostate cells.

Quantitative analysis of phenolic metabolites from different parts of Angelica keiskei by HPLC-ESI MS/MS and their xanthine oxidase inhibition.

PubMed

Kim, Dae Wook; Curtis-Long, Marcus J; Yuk, Heung Joo; Wang, Yan; Song, Yeong Hun; Jeong, Seong Hun; Park, Ki Hun

2014-06-15

Angelica keiskei is used as popular functional food stuff. However, quantitative analysis of this plant's metabolites has not yet been disclosed. The principal phenolic compounds (1-16) within A. keiskei were isolated, enabling us to quantify the metabolites within different parts of the plant. The specific quantification of metabolites (1-16) was accomplished by multiple reaction monitoring (MRM) using a quadruple tandem mass spectrometer. The limit of detection and limit of quantitation were calculated as 0.4-44 μg/kg and 1.5-148 μg/kg, respectively. Abundance and composition of these metabolites varied significantly across different parts of plant. For example, the abundance of chalcones (12-16) decreased as follows: root bark (10.51 mg/g)>stems (8.52 mg/g)>leaves (2.63 mg/g)>root cores (1.44 mg/g). The chalcones were found to be responsible for the xanthine oxidase (XO) inhibition shown by this plant. The most potent inhibitor, xanthoangelol inhibited XO with an IC50 of 8.5 μM. Chalcones (12-16) exhibited mixed-type inhibition characteristics. Copyright © 2013 Elsevier Ltd. All rights reserved.

Probe Into the Influence of Crosslinking on CO2 Permeation of Membranes

PubMed Central

Li, Jinghui; Chen, Zhuo; Umar, Ahmad; Liu, Yang; Shang, Ying; Zhang, Xiaokai; Wang, Yao

2017-01-01

Crosslinking is an effective way to fabricate high-selective CO2 separation membranes because of its unique crosslinking framework. Thus, it is essentially significant to study the influence of crosslinking degree on the permeation selectivities of CO2. Herein, we report a successful and facile synthesis of a series of polyethylene oxide (PEO)-based diblock copolymers (BCP) incorporated with an unique UV-crosslinkable chalcone unit using Reversible Addition-Fragmentation Chain Transfer Polymerization (RAFT) process. The membranes of as-prepared BCPs show superior carbon dioxide (CO2) separation properties as compared to nitrogen (N2) after UV-crosslinking. Importantly, the influence of different proportions of crosslinked chalcone on CO2 selectivities was systematically investigated, which revealed that CO2 selectivities increased obviously with the enhancement of chalcone fractions within a certain limit. Further, the CO2 selectivities of block copolymer with the best block proportion was studied by varying the crosslinking time which confirmed that the high crosslinking degree exhibited a better CO2/N2 (αCO2/N2) selectivities. A possible mechanism model revealing that the crosslinking degree played a key role in the gas separation process was also proposed. PMID:28051190

Pd (II) complexes of bidentate chalcone ligands: Synthesis, spectral, thermal, antitumor, antioxidant, antimicrobial, DFT and SAR studies

NASA Astrophysics Data System (ADS)

Gaber, Mohamed; Awad, Mohamed K.; Atlam, Faten M.

2018-05-01

The ligation behavior of two chalcone ligands namely, (E)-3-(4-chlorophenyl)-1-(pyridin-2-yl)prop-2-en-1-one (L1) and (E)-3-(4-methoxyphenyl)-1-(pyridin-2-yl)prop-2-en-1-one (L2), towards the Pd(II) ion is determined. The structures of the complexes are elucidated by elemental analysis, spectral methods (IR, electronic and NMR spectra) as well as the conductance measurements and thermal analysis. The metal complexes exhibit a square planar geometrical arrangement. The kinetic and thermodynamic parameters for some selected decomposition steps have been calculated. The antimicrobial, antioxidant and anticancer activities of the chalcones and their Pd(II) complexes have been evaluated. Molecular orbital computations are performed using DFT at B3LYP level with 6-31 + G(d) and LANL2DZ basis sets to access reliable results to the experimental values. The calculations are performed to obtain the optimized molecular geometry, charge density distribution, extent of distortion from regular geometry. Thermodynamic parameters for the investigated compounds are also studied. The calculations confirm that the investigated complexes have square planner geometry, which is in a good agreement with the experimental observation.

The effect of Zuccagnia punctata, an Argentine medicinal plant, on virulence factors from candida species.

PubMed

Gabriela, Nuño; Rosa, Alberto María; Catiana, Zampini Iris; Soledad, Cuello; Mabel, Ordoñez Roxana; Esteban, Sayago Jorge; Veronica, Baroni; Daniel, Wunderlin; Ines, Isla María

2014-07-01

Zuccagnia punctata Cav. has been used as a traditional medicine in Argentina for the treatment of bacterial and fungal infections. In this study, we evaluated the ability of Z. punctata extract (ZpE) and compounds isolated from it to inhibit the growth and virulence factors of Candida species. ZpE showed inhibitory activity against planktonic cells of all assayed Candida species with MIC values of 400 microg/mL and with MFC values between 400 and 1,200 microg/mL. The principal identified compounds by HPLC-MS/MS and UV-VIS were chalcones (2',4'-dihydroxy-3'-methoxychalcone, 2',4'- dihydroxychalcone), flavones (galangin, 3,7-dihydroxyflavone and chrysin) and flavanones (naringenin, 7-hydroxyflavanone and pinocembrine). These compounds were more effective as inhibitors than the extracts upon biofilm formation as well as on preformed Candida biofilm and yeast germ tube formation. Furthermore, ZpE and chalcones are able to inhibit exoenzymes, which are responsible for the invasion mechanisms of the pathogens. All these effects could moderate colonization, thereby suppressing the pathogen invasive potential. Our results indicate that ZpE and chalcones could be used in antifungal therapy.

New antimicrobial combinations: substituted chalcones- oxacillin against methicillin resistant Staphylococcus aureus

PubMed Central

Talia, Juan Manuel; Debattista, Nora Beatriz; Pappano, Nora Beatriz

2011-01-01

Staphylococcus aureus, the most virulent Staphylococcus species, is also the prevalent pathogen isolated from hospitalized patients and the second most common from patients in outpatient settings. In general, bacteria have the genetic ability to transmit and acquire resistance to drugs, which are utilized as therapeutic agents. Related studies of antimicrobial activity indicate that crude extracts containing flavonoids, triterpenes and steroids have showed significative activity against several Staphylococcus aureus strains. Combination effects between flavonoids and antibiotics also have been reported. The aim of the present work was to investigate in vitro synergism between several chalcones substituted in combination with oxacillin, an antibiotic used conventionally against S. aureus ATCC 43 300 that is resistant to meticillin, using the kinetic turbidimetric method developed earlier. The results were satisfactory for all assayed combinations and in accordance with the mechanism of bacteriostatic inhibition previously proposed, except for 2´,4´-dihydroxy-3´-methoxychalcone – oxacillin. The best combination was 2´,3´-dihydroxychalcone -oxacillin (MIC: 11.2 µg/mL). Further investigations are needed to characterize the interaction mechanism with antibiotics. Thus, chalcones – oxacillin combination could lead to the development of new antibiotics against methicillin resistant S. aureus infection. PMID:24031657

New antimicrobial combinations: substituted chalcones- oxacillin against methicillin resistant Staphylococcus aureus.

PubMed

Talia, Juan Manuel; Debattista, Nora Beatriz; Pappano, Nora Beatriz

2011-04-01

Staphylococcus aureus, the most virulent Staphylococcus species, is also the prevalent pathogen isolated from hospitalized patients and the second most common from patients in outpatient settings. In general, bacteria have the genetic ability to transmit and acquire resistance to drugs, which are utilized as therapeutic agents. Related studies of antimicrobial activity indicate that crude extracts containing flavonoids, triterpenes and steroids have showed significative activity against several Staphylococcus aureus strains. Combination effects between flavonoids and antibiotics also have been reported. The aim of the present work was to investigate in vitro synergism between several chalcones substituted in combination with oxacillin, an antibiotic used conventionally against S. aureus ATCC 43 300 that is resistant to meticillin, using the kinetic turbidimetric method developed earlier. The results were satisfactory for all assayed combinations and in accordance with the mechanism of bacteriostatic inhibition previously proposed, except for 2´,4´-dihydroxy-3´-methoxychalcone - oxacillin. The best combination was 2´,3´-dihydroxychalcone -oxacillin (MIC: 11.2 µg/mL). Further investigations are needed to characterize the interaction mechanism with antibiotics. Thus, chalcones - oxacillin combination could lead to the development of new antibiotics against methicillin resistant S. aureus infection.

Effects of chalcone derivatives on players of the immune system

PubMed Central

Lee, Jian Sian; Bukhari, Syed Nasir Abbas; Fauzi, Norsyahida Mohd

2015-01-01

The immune system is the defense mechanism in living organisms that protects against the invasion of foreign materials, microorganisms, and pathogens. It involves multiple organs and tissues in human body, such as lymph nodes, spleen, and mucosa-associated lymphoid tissues. However, the execution of immune activities depends on a number of specific cell types, such as B cells, T cells, macrophages, and granulocytes, which provide various immune responses against pathogens. In addition to normal physiological functions, abnormal proliferation, migration, and differentiation of these cells (in response to various chemical stimuli produced by invading pathogens) have been associated with several pathological disorders. The unwanted conditions related to these cells have made them prominent targets in the development of new therapeutic interventions against various pathological implications, such as atherosclerosis and autoimmune diseases. Chalcone derivatives exhibit a broad spectrum of pharmacological activities, such as immunomodulation, as well as anti-inflammatory, anticancer, antiviral, and antimicrobial properties. Many studies have been conducted to determine their inhibitory or stimulatory activities in immune cells, and the findings are of significance to provide a new direction for subsequent research. This review highlights the effects of chalcone derivatives in different types of immune cells. PMID:26316713

Activity of chalcones derived from 2,4,5-trimethoxybenzaldehyde against Meloidogyne exigua and in silico interaction of one chalcone with a putative caffeic acid 3-O-methyltransferase from Meloidogyne incognita.

PubMed

Nunes, Alexandro Silva; Campos, Vicente Paulo; Mascarello, Alessandra; Stumpf, Taisa Regina; Chiaradia-Delatorre, Louise Domenghini; Machado, Alan Rodrigues Teixeira; Santos Júnior, Helvécio Martins; Yunes, Rosendo Augusto; Nunes, Ricardo José; Oliveira, Denilson Ferreira

2013-12-01

Meloidogyne exigua is a parasitic nematode of plants that causes great losses to coffee farmers. In an effort to develop parasitic controls, 154 chalcones were synthesized and screened for activity against this nematode. The best results were obtained with (2E)-1-(4'-nitrophenyl)-3-(2,4,5-trimethoxyphenyl)prop-2-en-1-one (6) with a 50% lethal concentration (LC50) of 171 μg/ml against M. exigua second-stage juveniles, in comparison to the commercially-available nematicide carbofuran which had an LC50 of 260 μg/ml under the same conditions. When coffee plants were used, 6 reduced the nematode population to ~50% of that observed in control plants. To investigate the mechanism of action of 6, an in silico study was carried out, which indicated that 6 may act against M. exigua through inhibition of a putative caffeic acid 3-O-methyltransferase homodimer, the amino acid sequence of which was determined by examining the genome of Meloidogyne incognita. Copyright © 2013 Elsevier Inc. All rights reserved.

3'-Geranyl-mono-substituted chalcone Xanthoangelovl induces apoptosis in human leukemia K562 cells via activation of mitochondrial pathway.

PubMed

Teng, Yuou; Wang, Lixin; Liu, Huan; Yuan, Yuan; Zhang, Qian; Wu, Meng; Wang, Luyao; Wang, Haomeng; Liu, Zhen; Yu, Peng

2017-01-05

3'-Geranyl-mono-substituted chalcone Xanthoangelol (1b), a chalcone derivative, was previously reported to show selective cytotoxicity against human chronic myelogenous leukemia K562 cells with a half-maximal inhibitory concentration (IC 50 ) of 3.98 μM. In the present study, we investigated the molecular mechanism underlying the cytotoxicity of 1b in K562 cells. Treatment with compound 1b caused K562 cells to adopt a typical apoptotic morphology. Flow cytometric analysis also confirmed the presence of an apoptotic cell population following treatment of Annexin-V-FITC and propidium iodide (PI) double-labeled K562 cells with 1b. Furthermore, we observed dissipation of the mitochondrial membrane potential, caspase-3 activation, and a reduction of the Bcl-2/Bax ratio in these cells, which suggest that the mitochondrial apoptotic pathway is induced by 1b in K562 cells. Collectively, our findings demonstrate that compound 1b notably induces mitochondrial-mediated apoptosis in K562 cells, which might have a potential anticancer activity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Probe Into the Influence of Crosslinking on CO2 Permeation of Membranes

NASA Astrophysics Data System (ADS)

Li, Jinghui; Chen, Zhuo; Umar, Ahmad; Liu, Yang; Shang, Ying; Zhang, Xiaokai; Wang, Yao

2017-01-01

Crosslinking is an effective way to fabricate high-selective CO2 separation membranes because of its unique crosslinking framework. Thus, it is essentially significant to study the influence of crosslinking degree on the permeation selectivities of CO2. Herein, we report a successful and facile synthesis of a series of polyethylene oxide (PEO)-based diblock copolymers (BCP) incorporated with an unique UV-crosslinkable chalcone unit using Reversible Addition-Fragmentation Chain Transfer Polymerization (RAFT) process. The membranes of as-prepared BCPs show superior carbon dioxide (CO2) separation properties as compared to nitrogen (N2) after UV-crosslinking. Importantly, the influence of different proportions of crosslinked chalcone on CO2 selectivities was systematically investigated, which revealed that CO2 selectivities increased obviously with the enhancement of chalcone fractions within a certain limit. Further, the CO2 selectivities of block copolymer with the best block proportion was studied by varying the crosslinking time which confirmed that the high crosslinking degree exhibited a better CO2/N2 (αCO2/N2) selectivities. A possible mechanism model revealing that the crosslinking degree played a key role in the gas separation process was also proposed.

Synthesis and anti-proliferative activity of fluoro-substituted chalcones.

PubMed

Burmaoglu, Serdar; Algul, Oztekin; Anıl, Derya Aktas; Gobek, Arzu; Duran, Gulay Gulbol; Ersan, Ronak Haj; Duran, Nizami

2016-07-01

A series of novel fluoro-substituted chalcone derivatives have been synthesized. All synthesized compounds were characterized by (1)H nuclear magnetic resonance (NMR), (13)C NMR, and elemental analysis. Their anti-proliferative activities were evaluated against five cancer cells lines, namely, A549, A498, HeLa, A375, and HepG2 using the MTT method. Most of the compounds showed moderate to high activity with IC50 values in the range of 0.029-0.729μM. Of all the synthesized compounds, 10 and 19 exhibited the most potent anti-proliferative activities against cancer cells, and 10 was identified as the most promising compound. Copyright © 2016 Elsevier Ltd. All rights reserved.

Solvent-free synthesis, spectral correlations and antimicrobial activities of some aryl E 2-propen-1-ones

NASA Astrophysics Data System (ADS)

Sathiyamoorthi, K.; Mala, V.; Sakthinathan, S. P.; Kamalakkannan, D.; Suresh, R.; Vanangamudi, G.; Thirunarayanan, G.

2013-08-01

Totally 38 aryl E 2-propen-1-ones including nine substituted styryl 4-iodophenyl ketones have been synthesised using solvent-free SiO2-H3PO4 catalyzed Aldol condensation between respective methyl ketones and substituted benzaldehydes under microwave irradiation. The yields of the ketones are more than 80%. The synthesised chalcones were characterized by their analytical, physical and spectroscopic data. The spectral frequencies of synthesised substituted styryl 4-iodophenyl ketones have been correlated with Hammett substituent constants, F and R parameters using single and multi-linear regression analysis. The antimicrobial activities of 4-iodophenyl chalcones have been studied using Bauer-Kirby method.

Synthesis, characterization and nonlinear optical properties of symmetrically substituted dibenzylideneacetone derivatives

NASA Astrophysics Data System (ADS)

Sunil Kumar Reddy, N.; Badam, Rajashekar; Sattibabu, Romala; Molli, Muralikrishna; Sai Muthukumar, V.; Siva Sankara Sai, S.; Rao, G. Nageswara

2014-11-01

We report here the nonlinear optical (NLO) properties of eight bis-chalcones of D-π-A-π-D type. These dibenzylideneacetone (DBA) derivatives are synthesized by Claisen-Schmidt reaction. The compounds are characterized by UV-vis, FTIR, 1H NMR, 13C NMR, mass spectroscopy and powder XRD. By substituting different groups (electron withdrawing and electron donating) at 'para' and 'meta' positions of the aromatic ring, we observed an enhancement in second harmonic generation with substitution at 'para' position. These compounds have also showed higher two-photon absorption compared to other chalcones reported in literature. These compounds, exhibiting both second and third order NLO effects, are plausible candidate materials in photonic devices.

Synthesis and antibacterial evaluation of novel cationic chalcone derivatives possessing broad spectrum antibacterial activity.

PubMed

Chu, Wen-Chao; Bai, Peng-Yan; Yang, Zhao-Qing; Cui, De-Yun; Hua, Yong-Gang; Yang, Yi; Yang, Qian-Qian; Zhang, En; Qin, Shangshang

2018-01-01

There is an urgent need to identify new antibiotics with novel mechanisms that combat antibiotic resistant bacteria. Herein, a series of chalcone derivatives that mimic the essential properties of cationic antimicrobial peptides were designed and synthesized. Antibacterial activities against drug-sensitive bacteria, including Staphylococcus aureus, Enterococcus faecalis, Escherichia coli and Salmonella enterica, as well as clinical multiple drug resistant isolates of methicillin-resistant S. aureus (MRSA), KPC-2-producing and NDM-1-producing Carbapenem-resistant Enterobacteriaceae were evaluated. Representative compounds 5a (MIC: 1 μg/mL against S. aureus, 0.5 μg/mL against MRSA) and 5g (MIC: 0.5 μg/mL against S. aureus, 0.25 μg/mL against MRSA) showed good bactericidal activity against both Gram-positive and Gram-negative bacteria, including the drug-resistant species MRSA, KPC and NDM. These membrane-active antibacterial compounds were demonstrated to reduce the viable cell counts in bacterial biofilms effectively and do not induce the development of resistance in bacteria. Additionally, these representative molecules exhibited negligible toxicity toward mammalian cells at a suitable concentration. The combined results indicate that this series of cationic chalcone derivatives have potential therapeutic effects against bacterial infections. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Chalcone scaffolds as anti-infective agents: structural and molecular target perspectives.

PubMed

Mahapatra, Debarshi Kar; Bharti, Sanjay Kumar; Asati, Vivek

2015-08-28

In recent years, widespread outbreak of numerous infectious diseases across the globe has created havoc among the population. Particularly, the inhabitants of tropical and sub-tropical regions are mainly affected by these pathogens. Several natural and (semi) synthetic chalcones deserve the credit of being potential anti-infective candidates that inhibit various parasitic, malarial, bacterial, viral, and fungal targets like cruzain-1/2, trypanopain-Tb, trans-sialidase, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), fumarate reductase, falcipain-1/2, β-hematin, topoisomerase-II, plasmepsin-II, lactate dehydrogenase, protein kinases (Pfmrk and PfPK5), and sorbitol-induced hemolysis, DEN-1 NS3, H1N1, HIV (Integrase/Protease), protein tyrosine phosphatase A/B (Ptp-A/B), FtsZ, FAS-II, lactate/isocitrate dehydrogenase, NorA efflux pump, DNA gyrase, fatty acid synthase, chitin synthase, and β-(1,3)-glucan synthase. In this review, a comprehensive study (from Jan. 1982 to May 2015) of the structural features of anti-infective chalcones, their mechanism of actions (MOAs) and structure activity relationships (SARs) have been highlighted. With the knowledge of molecular targets, structural insights and SARs, this review may be helpful for (medicinal) chemists to design more potent, safe, selective and cost effective anti-infective agents. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Novel Halogenated Pyrazine-Based Chalcones as Potential Antimicrobial Drugs.

PubMed

Kucerova-Chlupacova, Marta; Vyskovska-Tyllova, Veronika; Richterova-Finkova, Lenka; Kunes, Jiri; Buchta, Vladimir; Vejsova, Marcela; Paterova, Pavla; Semelkova, Lucia; Jandourek, Ondrej; Opletalova, Veronika

2016-10-27

Chalcones, i.e., compounds with the chemical pattern of 1,3-diphenylprop-2-en-1-ones, exert a wide range of bio-activities, e.g., antioxidant, anti-inflammatory, anticancer, anti-infective etc. Our research group has been focused on pyrazine analogues of chalcones; several series have been synthesized and tested in vitro on antifungal and antimycobacterial activity. The highest potency was exhibited by derivatives with electron withdrawing groups (EWG) in positions 2 and 4 of the ring B. As halogens also have electron withdrawing properties, novel halogenated derivatives were prepared by Claisen-Schmidt condensation. All compounds were submitted for evaluation of their antifungal and antibacterial activity, including their antimycobacterial effect. In the antifungal assay against eight strains of selected fungi, growth inhibition of Candida glabrata and Trichophyton interdigitale (formerly T. mentagrophytes ) was shown by non-alkylated derivatives with 2-bromo or 2-chloro substitution. In the panel of selected bacteria, 2-chloro derivatives showed the highest inhibitory effect on Staphylococcus sp. In addition, all products were also screened for their antimycobacterial activity against Mycobacterium tuberculosis H37RV My 331/88, M. kansasii My 235/80, M. avium 152/80 and M. smegmatis CCM 4622. Some of the examined compounds, inhibited growth of M. kansasii and M. smegmatis with minimum inhibitory concentrations (MICs) comparable with those of isoniazid.

New structure–activity relationships of chalcone inhibitors of breast cancer resistance protein: polyspecificity toward inhibition and critical substitutions against cytotoxicity

PubMed Central

Rangel, Luciana Pereira; Winter, Evelyn; Gauthier, Charlotte; Terreux, Raphaël; Chiaradia-Delatorre, Louise D; Mascarello, Alessandra; Nunes, Ricardo J; Yunes, Rosendo A; Creczynski-Pasa, Tania B; Macalou, Sira; Lorendeau, Doriane; Baubichon-Cortay, Hélène; Ferreira-Pereira, Antonio; Di Pietro, Attilio

2013-01-01

Adenosine triphosphate-binding cassette subfamily G member 2 (ABCG2) plays a major role in cancer cell multidrug resistance, which contributes to low eifficacy of chemotherapy. Chalcones were recently found to be potent and specific inhibitors, but unfortunately display a significant cytotoxicity. A cellular screening against ABCG2-mediated mitoxantrone efflux was performed here by flow cytometry on 54 chalcone derivatives from three different series with a wide panel of substituents. The identified leads, with submicromolar IC50 (half maximal inhibitory concentration) values, showed that the previously identified 2′-OH-4′,6′-dimethoxyphenyl, as A-ring, could be efficiently replaced by a 2′-naphthyl group, or a 3′,4′-methylenedioxyphenyl with lower affinity. Such a structural variability indicates 3polyspecificity of the multidrug transporter for inhibitors. At least two methoxyl groups were necessary on B-ring for optimal inhibition, but substitution at positions 3, 4, and 5 induced cytotoxicity. The presence of a large O-benzyl substituent at position 4 and a 2′-naphthyl as A-ring markedly decreased the cytotoxicity, giving a high therapeutic ratio, which constitutes a critical requirement for future in-vivo assays in animal models. PMID:24109177

Synthesis and evaluation of modified chalcone based p53 stabilizing agents.

PubMed

Iftikhar, Sunniya; Khan, Sardraz; Bilal, Aishah; Manzoor, Safia; Abdullah, Muhammad; Emwas, Abdel-Hamid; Sioud, Salim; Gao, Xin; Chotana, Ghayoor Abbas; Faisal, Amir; Saleem, Rahman Shah Zaib

2017-09-01

Tumor suppressor protein p53 induces cell cycle arrest and apoptotic cell death in response to various cellular stresses thereby preventing cancer development. Activation and stabilization of p53 through small organic molecules is, therefore, an attractive approach for the treatment of cancers retaining wild-type p53. In this context, a series of nineteen chalcones with various substitution patterns of functional groups including chloro, fluoro, methoxy, nitro, benzyloxy, 4-methyl benzyloxy was prepared using Claisen-Schmidt condensation. The compounds were characterized using NMR, HRMS, IR and melting points. Evaluation of synthesized compounds against human colorectal (HCT116) and breast (CAL-51) cancer cell lines revealed potent antiproliferative activities. Nine compounds displayed GI 50 values in the low micromolar to submicromolar range; for example (E)-1-phenyl-3-(3,4,5-trimethoxyphenyl)prop-2-en-1-one (SSE14108) showed GI 50 of 0.473±0.043µM against HCT116 cells. Further analysis of these compounds revealed that (E)-3-(4-chlorophenyl)-1-phenylprop-2-en-1-one (SSE14105) and (E)-3-(4-methoxyphenyl)-1-phenylprop-2-en-1-one (SSE14106) caused rapid (4 and 8-h post-treatment) accumulation of p53 in HCT116 cells similar to its induction by positive control, Nutlin-3. Such activities were absent in 3-(4-methoxyphenyl)propiophenone (SSE14106H2) demonstrating the importance of conjugated ketone for antiproliferative and p53 stabilizing activity of the chalcones. We further evaluated p53 levels in the presence of cycloheximide (CHX) and the results showed that the p53 stabilization was regulated at post-translational level through blockage of its degradation. These chalcones can, therefore, act as fragment leads for further structure optimization to obtain more potent p53 stabilizing agents with enhanced anti-proliferative activities. Copyright © 2017 Elsevier Ltd. All rights reserved.

Solid state structural investigations of the bis(chalcone) compound with single crystal X-ray crystallography, DFT, gamma-ray spectroscopy and chemical spectroscopy methods

NASA Astrophysics Data System (ADS)

Yakalı, Gül; Biçer, Abdullah; Eke, Canel; Cin, Günseli Turgut

2018-04-01

A bis(chalcone), (2E,6E)-2,6-bis((E)-3phenylallidene)cyclohexanone, was characterized by 1H NMR, 13C NMR, FTIR, UV-Vis spectroscopy, gamma-ray spectroscopy and single crystal X- ray structural analysis. The optimized molecular structure of the compound is calculated using DFT/B3LYP with 6-31G (d,p) level. The calculated geometrical parameters are in good agreement with the experimental data obtained from our reported X-ray structure. The powder and single crystal compounds were gama-irradiated using clinical electron linear accelerator and 60Co gamma-ray source, respectively. Spectral studies (1H NMR, 13C NMR, FTIR and UV-Vis) of powder chalcone compound were also investigated before and after irradiation. Depending on the irradiation notable changes were observed in spectral features powder sample. Single crystal X-ray diffraction investigation shows that both unirradiated and irradiated single crystal samples crystallizes in a orthorhombic crystal system in the centrosymmetric space group Pbcn and exhibits an C-H..O intramolecular and intermolecular hydrogen bonds. The crystal packing is stabilised by strong intermolecular bifurcate C-H..O hydrogen bonds and π…π stacking interactions. The asymmetric unit of the title compound contains one-half of a molecule. The other half of the molecule is generated with (1-x,y,-3/2-z) symmetry operator. The molecule is almost planar due to having π conjugated system of chalcones. However, irradiated single crystal compound showed significant changes lattice parameters, crystal volume and density. According to results of gamma-ray spectroscopy, radioactive elements of powder compound which are 123Sb(n,g),124Sb,57Fe(g,p),56Mn, 55Mn(g,n), and 54Mn were determined using photoactivation analysis. However, the most intensive gamma-ray energy signals are 124Sb.

Identification of potential anti-infectives against Staphylococcus aureus using a Caenorhabditis elegans infection model

NASA Astrophysics Data System (ADS)

Kong, Cin; Rahman, Noorsaadah Abd; Nathan, Sheila

2014-09-01

The alarming increase of antibiotic-resistant Staphylococcus aureus and a delay in antibiotics development point to the need for novel therapeutic approaches to combat infection. To discover novel anti-infective agents, we screened a number of synthetic compounds comprising mainly of chalcone derivatives to explore their potential in promoting the survival of the nematode Caenorhabditis elegans upon infection by S. aureus. Screening of seven chalcone derivatives using both agar- and liquid-based assays revealed three positive hits that significantly prolonged the survival of S. aureus-infected nematodes. All the hits did not interfere with bacterial growth in vitro, proposing that the three compounds identified most probably act through mechanisms distinct from conventional antibiotics that target bacterial replication.

Antiplasmodial activity of novel keto-enamine chalcone-chloroquine based hybrid pharmacophores.

PubMed

Sashidhara, Koneni V; Kumar, Manoj; Modukuri, Ram K; Srivastava, Rajeev Kumar; Soni, Awakash; Srivastava, Kumkum; Singh, Shiv Vardan; Saxena, J K; Gauniyal, Harsh M; Puri, Sunil K

2012-05-01

A series of novel keto-enamine chalcone-chloroquine based hybrids were synthesized following new methodology developed in our laboratory. The synthesized compounds were screened against chloroquine sensitive strain (3D7) of Plasmodium falciparum in an in vitro model. Some of the compounds were showing comparable antimalarial activity at par with chloroquine. Compounds with significant in vitro antimalarial activity were then evaluated for their in vivo efficacy in Swiss mice against Plasmodium yoelii (chloroquine resistant N-67 strain), wherein compounds 25 and 27 each showed an in vivo suppression of 99.9% parasitaemia on day 4. Biochemical studies reveal that inhibition of hemozoin formation is the primary mechanism of action of these analogues. Copyright © 2012 Elsevier Ltd. All rights reserved.

α-Fluoro-α-nitro(phenylsulfonyl)methane as a fluoromethyl pronucleophile: Efficient stereoselective Michael addition to chalcones

PubMed Central

Prakash, G. K. Surya; Wang, Fang; Stewart, Timothy; Mathew, Thomas; Olah, George A.

2009-01-01

Highly efficient stereoselective 1,4-addition of racemic α-fluoro-α-nitro(phenylsulfonyl)methane (FNSM) as a fluoromethyl pronucleophile to α,β-unsaturated ketones using a wide range of chiral organobifunctional catalysts under moderate conditions in the absence of an additional base has been achieved. A series of catalysts was screened for the enantioselective addition of FNSM to chalcones and the catalysts CN I, CD I, QN I-IV, and QD I were found to enable this reaction, successfully providing exclusive 1,4-addition products stereoselectively in high yields (conversion, diastereomeric ratio, and enantiomeric excess). Studies involving a model reaction and systematic analysis of the absolute configuration support the suggested mechanism. PMID:19237559

Two structurally distinct chalcone dimers from Helichrysum zivojinii and their activities in cancer cell lines.

PubMed

Aljančić, Ivana S; Vučković, Ivan; Jadranin, Milka; Pešić, Milica; Dorđević, Iris; Podolski-Renić, Ana; Stojković, Sonja; Menković, Nebojša; Vajs, Vlatka E; Milosavljević, Slobodan M

2014-02-01

Dimers tomoroside A (1) and tomoroside B (2) of the co-occuring known chalcone monomer (3), along with the seven known flavonoid glucosides (4-10), were isolated from the aerial parts of Helichrysum zivojinii Černjavski & Soška. The structures of the isolated compounds were elucidated by spectroscopic techniques. Compound 1 inhibited topo IIα and hif-1α expression and stimulated doxorubicin anticancer effect, while 2 increased the expression of hif-1α, probably acting as antioxidant and redox status modulator. Notably, 2 synergized with Tipifarnib showing potential to improve the action of this new chemotherapeutic involved in the modulation of mitogene activated protein (MAP) kinase signaling pathway. Copyright © 2013 Elsevier Ltd. All rights reserved.

Substituent Dependence of Third-Order Optical Nonlinearity in Chalcone Derivatives

NASA Astrophysics Data System (ADS)

Kiran, Anthony John; Satheesh Rai, Nooji; Chandrasekharan, Keloth; Kalluraya, Balakrishna; Rotermund, Fabian

2008-08-01

The third-order nonlinear optical properties of derivatives of dibenzylideneacetone were investigated using the single beam z-scan technique at 532 nm. A strong dependence of third-order optical nonlinearity on electron donor and acceptor type of substituents was observed. An enhancement in χ(3)-value of one order of magnitude was achieved upon the substitution of strong electron donors compared to that of the molecule substituted with an electron acceptor. The magnitude of nonlinear refractive index of these chalcones is as high as of 10-11 esu. Their nonlinear optical coefficients are larger than those of widely used thiophene oligomers and trans-1-[p-(p-dimethylaminobenzyl-azo)-benzyl]-2-(N-methyl-4-pyridinium)-ethene iodide (DABA-PEI) organic compounds.

Chalcone-based carbamates for Alzheimer's disease treatment.

PubMed

Rampa, Angela; Montanari, Serena; Pruccoli, Letizia; Bartolini, Manuela; Falchi, Federico; Feoli, Alessandra; Cavalli, Andrea; Belluti, Federica; Gobbi, Silvia; Tarozzi, Andrea; Bisi, Alessandra

2017-05-01

Alzheimer's disease is a still untreatable multifaceted pathology, and drugs able to stop or reverse its progression are urgently needed. In this picture, the recent reformulation of the cholinergic hypothesis renewed the interest for acetylcholinesterase inhibitors. In this paper, a series of naturally inspired chalcone-based carbamates was designed to target cholinesterase enzymes and possibly generate fragments endowed with neuroprotective activity in situ. Results & methodology: All compounds presented in this study showed nanomolar potency for cholinesterase inhibition. Notably, fragment 11d also displayed an interesting neuroprotective profile. These new derivatives are able to simultaneously modulate different key targets involved in Alzheimer's disease, and could be regarded as promising starting points for the development of disease-modifying drug candidates. [Formula: see text].

Anion channels and the stimulation of anthocyanin accumulation by blue light in Arabidopsis seedlings

NASA Technical Reports Server (NTRS)

Noh, B.; Spalding, E. P.; Evans, M. H. (Principal Investigator)

1998-01-01

Activation of anion channels by blue light begins within seconds of irradiation in seedlings and is related to the ensuing growth inhibition. 5-Nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB) is a potent, selective, and reversible blocker of these anion channels in Arabidopsis thaliana. Here we show that 20 microM NPPB blocked 72% of the blue-light-induced accumulation of anthocyanin pigments in seedlings. Feeding biosynthetic intermediates to wild-type and tt5 seedlings provided evidence that NPPB prevented blue light from up-regulating one or more steps between and including phenylalanine ammonia lyase and chalcone isomerase. NPPB was found to have no significant effect on the blue-light-induced increase in transcript levels of PAL1, CHS, CHI, or DFR, which are genes that encode anthocyanin-biosynthetic enzymes. Immunoblots revealed that NPPB also did not inhibit the accumulation of the chalcone synthase, chalcone isomerase, or flavanone-3-hydroxylase proteins. This is in contrast to the reduced anthocyanin accumulation displayed by a mutant lacking the HY4 blue-light receptor, as hy4 displayed reduced expression of the above enzymes. Taken together, the data indicate that blue light acting through HY4 leads to an increase in the amount of biosynthetic enzymes but blue light must also act through a separate, anion-channel-dependent system to create a fully functional biosynthetic pathway.

Metabolome analysis of biosynthetic mutants reveals a diversity of metabolic changes and allows identification of a large number of new compounds in Arabidopsis.

PubMed

Böttcher, Christoph; von Roepenack-Lahaye, Edda; Schmidt, Jürgen; Schmotz, Constanze; Neumann, Steffen; Scheel, Dierk; Clemens, Stephan

2008-08-01

Metabolomics is facing a major challenge: the lack of knowledge about metabolites present in a given biological system. Thus, large-scale discovery of metabolites is considered an essential step toward a better understanding of plant metabolism. We show here that the application of a metabolomics approach generating structural information for the analysis of Arabidopsis (Arabidopsis thaliana) mutants allows the efficient cataloging of metabolites. Fifty-six percent of the features that showed significant differences in abundance between seeds of wild-type, transparent testa4, and transparent testa5 plants could be annotated. Seventy-five compounds were structurally characterized, 21 of which could be identified. About 40 compounds had not been known from Arabidopsis before. Also, the high-resolution analysis revealed an unanticipated expansion of metabolic conversions upstream of biosynthetic blocks. Deficiency in chalcone synthase results in the increased seed-specific biosynthesis of a range of phenolic choline esters. Similarly, a lack of chalcone isomerase activity leads to the accumulation of various naringenin chalcone derivatives. Furthermore, our data provide insight into the connection between p-coumaroyl-coenzyme A-dependent pathways. Lack of flavonoid biosynthesis results in elevated synthesis not only of p-coumarate-derived choline esters but also of sinapate-derived metabolites. However, sinapoylcholine is not the only accumulating end product. Instead, we observed specific and sophisticated changes in the complex pattern of sinapate derivatives.

Genome-Wide Identification of Chalcone Reductase Gene Family in Soybean: Insight into Root-Specific GmCHRs and Phytophthora sojae Resistance

PubMed Central

Sepiol, Caroline J.; Yu, Jaeju; Dhaubhadel, Sangeeta

2017-01-01

Soybean (Glycine max [L.] Merr) is one of the main grain legumes worldwide. Soybean farmers lose billions of dollars’ worth of yield annually due to root and stem rot disease caused by the oomycete Phytophthora sojae. Many strategies have been developed to combat the disease, however, these methods have proven ineffective in the long term. A more cost effective and durable approach is to select a trait naturally found in soybean that can increase resistance. One such trait is the increased production of phytoalexin glyceollins in soybean. Glyceollins are isoflavonoids, synthesized via the legume-specific branch of general phenylpropanoid pathway. The first key enzyme exclusively involved in glyceollin synthesis is chalcone reductase (CHR) which coacts with chalcone synthase for the production of isoliquiritigenin, the precursor for glyceollin biosynthesis. Here we report the identification of 14 putative CHR genes in soybean where 11 of them are predicted to be functional. Our results show that GmCHRs display tissue-specific gene expression, and that only root-specific GmCHRs are induced upon P. sojae infection. Among 4 root-specific GmCHRs, GmCHR2A is located near a QTL that is linked to P. sojae resistance suggesting GmCHR2A as a novel locus for partial resistance that can be utilized for resistance breeding. PMID:29270182

Identification of chalcone isomerase in the basal land plants reveals an ancient evolution of enzymatic cyclization activity for synthesis of flavonoids

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cheng, Ai-Xia; Zhang, Xuebin; Han, Xiao-Juan

Flavonoids ubiquitously distribute to the terrestrial plants and chalcone isomerase (CHI)- catalyzed intramolecular and stereospecific cyclization of chalcones is a committed step in the production of flavonoids. However, so far the bona fide CHIs are found only in vascular plants, and their origin and evolution remains elusive. We conducted transcriptomic and/or genomic sequence search, subsequent phylogenetic analysis, and detailed biochemical and genetic characterization to explore the potential existence of CHI proteins in the basal bryophyte liverwort species and the lycophyte Selaginella moellendorffii. We found that both liverwort and Selaginella species possess canonical CHI-fold proteins that cluster with their corresponding highermore » plant counterparts. Among them, some members exhibited bona fide CHI activity, which catalyze stereospecific cyclization of both 60- hydroxychalcone and 60-deoxychalcone, yielding corresponding 5-hydroxy and 5- deoxyflavanones, resembling the typical type II CHIs currently known to be ‘specific’ for legume plants. Expressing those primitive bona fide CHIs in the Arabidopsis chi mutant restores the seed coat transparent testa phenotype and the accumulation of flavonoids. These findings, in contrast to our current understanding of the evolution of enzymatic CHIs, suggest that emergence of the bona fide type II CHIs is an ancient evolution event that occurred before the divergence of liverwort lineages.« less

Anti-tumour activity of a novel coumarin-chalcone hybrid is mediated through intrinsic apoptotic pathway by inducing PUMA and altering Bax/Bcl-2 ratio.

PubMed

Singh, Neetu; Sarkar, Jayanta; Sashidhara, Koneni V; Ali, Shakir; Sinha, Sudhir

2014-06-01

Coumarins and chalcones are secondary plant metabolites which have shown an array of pharmacological properties including anti-tumour activity. We have previously reported on the synthesis and anti-proliferative activity of a series of novel coumarin-chalcone hybrids. Now we report on the in vivo efficacy as well as mechanism of action of the most potent molecule of the series, S009-131. Oral administration of this molecule resulted in regression of tumours induced by HeLa cell xenografts in nod SCID mice. The molecule inhibited proliferation of cervical cancer cells (HeLa and C33A) by inducing apoptosis and arresting cell cycle at G2/M phase. Apoptosis was induced through induction of caspase-dependent intrinsic pathway and alterations in the cellular levels of Bcl-2 family proteins. The mitochondrial transmembrane potential got highly depleted in S009-131 treated cells due to an increase in Bax/Bcl-2 ratio and intracellular ROS. The molecule induced release of cytochrome c into the cytosol and activation of initiator caspase-9 and executioner caspases-3/7. Tumour suppressor protein p53 and its transcriptional target PUMA were up regulated, suggesting their role in mediating the cell death. These results suggest that S009-131 is a potent candidate for the chemotherapy of cervical carcinoma.

Identification of chalcone isomerase in the basal land plants reveals an ancient evolution of enzymatic cyclization activity for synthesis of flavonoids

DOE PAGES

Cheng, Ai-Xia; Zhang, Xuebin; Han, Xiao-Juan; ...

2017-10-30

Flavonoids ubiquitously distribute to the terrestrial plants and chalcone isomerase (CHI)- catalyzed intramolecular and stereospecific cyclization of chalcones is a committed step in the production of flavonoids. However, so far the bona fide CHIs are found only in vascular plants, and their origin and evolution remains elusive. We conducted transcriptomic and/or genomic sequence search, subsequent phylogenetic analysis, and detailed biochemical and genetic characterization to explore the potential existence of CHI proteins in the basal bryophyte liverwort species and the lycophyte Selaginella moellendorffii. We found that both liverwort and Selaginella species possess canonical CHI-fold proteins that cluster with their corresponding highermore » plant counterparts. Among them, some members exhibited bona fide CHI activity, which catalyze stereospecific cyclization of both 60- hydroxychalcone and 60-deoxychalcone, yielding corresponding 5-hydroxy and 5- deoxyflavanones, resembling the typical type II CHIs currently known to be ‘specific’ for legume plants. Expressing those primitive bona fide CHIs in the Arabidopsis chi mutant restores the seed coat transparent testa phenotype and the accumulation of flavonoids. These findings, in contrast to our current understanding of the evolution of enzymatic CHIs, suggest that emergence of the bona fide type II CHIs is an ancient evolution event that occurred before the divergence of liverwort lineages.« less

Antimicrobial effects of Piper hispidum extract, fractions and chalcones against Candida albicans and Staphylococcus aureus.

PubMed

Costa, G M; Endo, E H; Cortez, D A G; Nakamura, T U; Nakamura, C V; Dias Filho, B P

2016-09-01

Three chalcones, 2'-hydroxy-4,4',6'-trimethoxychalcone, 2'-hydroxy-4,4',6'-tetramethoxychalcone, and 3,2'-dihydroxy-4,4',6'-trimethoxychalcone, were isolated from the leaves of Piper hispidum in a bioguided fractionation of crude extract. The antimicrobial activity of crude extract of P. hispidum leaves was determined against bacteria Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, Staphylococcus aureus and yeasts Candida albicans, C. parapsilosis and C. tropicalis. Fractions and chalcones were tested against C. albicans and S. aureus. The checkerboard assay was performed to assess synergic interactions between extract and antifungal drugs, and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) reduction assay was used to evaluate anti-biofilm effects of extract. The extract was active against yeasts, S. aureus and B. subtilis with MIC values between 15.6 and 62.5μg/mL. Synergistic effects of extract associated with fluconazole and nystatin were observed against C. albicans, with fractional inhibitory concentration indices of 0.37 and 0.24, respectively. The extract was also effective against C. albicans and S. aureus biofilm cells at concentrations of 62.5 and 200μg/mL, respectively. Thus, P. hispidum may be a possible source of bioactive substances with antimicrobial properties. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Disruption of endolysosomal trafficking pathways in glioma cells by methuosis-inducing indole-based chalcones.

PubMed

Mbah, Nneka E; Overmeyer, Jean H; Maltese, William A

2017-06-01

Methuosis is a form of non-apoptotic cell death involving massive vacuolization of macropinosome-derived endocytic compartments, followed by a decline in metabolic activity and loss of membrane integrity. To explore the induction of methuosis as a potential therapeutic strategy for killing cancer cells, we have developed small molecules (indole-based chalcones) that trigger this form of cell death in glioblastoma and other cancer cell lines. Here, we report that in addition to causing fusion and expansion of macropinosome compartments, the lead compound, 3-(5-methoxy-2-methyl-1H-indol-3-yl)-1-(4-pyridinyl)-2-propen-1-one (MOMIPP), disrupts vesicular trafficking at the lysosomal nexus, manifested by impaired degradation of EGF and LDL receptors, defective processing of procathepsins, and accumulation of autophagosomes. In contrast, secretion of the ectodomain derived from a prototypical type-I membrane glycoprotein, β-amyloid precursor protein, is increased rather than diminished. A closely related MOMIPP analog, which causes substantial vacuolization without reducing cell viability, also impedes cathepsin processing and autophagic flux, but has more modest effects on receptor degradation. A third analog, which causes neither vacuolization nor loss of viability, has no effect on endolysosomal trafficking. The results suggest that differential cytotoxicity of structurally similar indole-based chalcones is related, at least in part, to the severity of their effects on endolysosomal trafficking pathways.

Crucial role of molecular planarity on the second order nonlinear optical property of pyridine based chalcone single crystals

NASA Astrophysics Data System (ADS)

Menezes, Anthoni Praveen; Jayarama, A.; Ng, Seik Weng

2015-05-01

An efficient nonlinear optical material 2E-3-(4-bromophenyl)-1-(pyridin-3-yl) prop-2-en-1-one (BPP) was synthesized and single crystals were grown using slow evaporation solution growth technique at room temperature. Grown crystal had prismatic morphology and its structure was confirmed by various spectroscopic studies, elemental analysis, and single crystal X-ray diffraction (XRD) technique. The single crystal XRD of the crystal showed that BPP crystallizes in monoclinic system with noncentrosymmetric space group P21 and the cell parameters are a = 5.6428(7) Å, b = 3.8637(6) Å, c = 26.411(2) Å, β = 97.568(11) deg and v = 575.82(12) Å3. The UV-Visible spectrum reveals that the crystal is optically transparent and has high optical energy band gap of 3.1 eV. The powder second harmonic generation efficiency (SHG) of BPP is 6.8 times that of KDP. From thermal analysis it is found that the crystal melts at 139 °C and decomposes at 264 °C. High optical transparency down to blue region, higher powder SHG efficiency and better thermal stability than that of urea makes this chalcone derivative a promising candidate for SHG applications. Furthermore, effect of molecular planarity on SHG efficiency and role of pyridine ring adjacent to carbonyl group in forming noncentrosymmetric crystal systems of chalcone family is also discussed.

Comparison of the effects of selected chalcones, dihydrochalcones and some cyclic flavonoids on mitochondrial outer membrane determined by fluorescence spectroscopy.

PubMed

Tomecková, Vladimíra; Guzy, Juraj; Kusnír, Jaroslav; Fodor, Krisztina; Mareková, Mária; Chavková, Zenóbia; Perjési, Pál

2006-11-30

The effect on mitochondrial outer membrane of 4-hydroxychalcone (1), the cyclic chalcone analogues E-2-(4'-hydroxybenzylidene)-1-indanone (2a) and E-2-(4'-hydroxybenzylidene)-1-tetralone (2b), the dihydrochalcones phloretin (3a) and phloridzin (3b), the flavanones naringenin (4a) and naringin (4b), and the flavonol quercetin (5) was investigated by fluorescence spectroscopy. Excitation and emission fluorescence spectra of each flavonoid and synthetic analogue were recorded in respiration medium containing 1 mM succinate. Initial interaction of the compounds with the outer mitochondrial membrane was investigated by recording their fluorescence polarization in the presence of rat liver mitochondria. Most of the compounds displayed an elevated fluorescence polarization on mixing with mitochondria at the zero time point. During the investigated 20 min period the initial fluorescence polarization values remained constant (1, 2a), or a gradual depression of the measured polarization values could be observed (2b, 3a, 4b, 5). In the case of naringenin (4a), however, similar to the previously investigated seven-membered cyclic chalcone analogue E-2-(4 -methoxybenzylidene)-1-benzosuberone, a slight, continuous increase of fluorescence polarization could be detected during the 20 min experiment. Phloridzin (3b) showed an increased fluorescence polarization in first 10 min, which was slightly depressed by the 20 min time point.

Discovery of new MD2 inhibitor from chalcone derivatives with anti-inflammatory effects in LPS-induced acute lung injury

PubMed Central

Zhang, Yali; Wu, Jianzhang; Ying, Shilong; Chen, Gaozhi; Wu, Beibei; Xu, Tingting; Liu, Zhiguo; Liu, Xing; Huang, Lehao; Shan, Xiaoou; Dai, Yuanrong; Liang, Guang

2016-01-01

Acute lung injury (ALI) is a life-threatening acute inflammatory disease with limited options available for therapy. Myeloid differentiation protein 2, a co-receptor of TLR4, is absolutely required for TLR4 sense LPS, and represents an attractive target for treating severe inflammatory diseases. In this study, we designed and synthesized 31 chalcone derivatives that contain the moiety of (E)-4-phenylbut-3-en-2-one, which we consider the core structure of current MD2 inhibitors. We first evaluated the anti-inflammatory activities of these compounds in MPMs. For the most active compound 20, we confirmed that it is a specific MD2 inhibitor through a series of biochemical experiments and elucidated that it binds to the hydrophobic pocket of MD2 via hydrogen bonds with Arg90 and Tyr102 residues. Compound 20 also blocked the LPS-induced activation of TLR4/MD2 -downstream pro-inflammatory MAPKs/NF-κB signaling pathways. In a rat model with ALI induced by intracheal LPS instillation, administration with compound 20 exhibited significant protective effect against ALI, accompanied by the inhibition of TLR4/MD2 complex formation in lung tissues. Taken together, the results of this study suggest the specific MD2 inhibitor from chalcone derivatives we identified is a potential candidate for treating acute inflammatory diseases. PMID:27118147

A mutation in the rice chalcone isomerase gene causes the golden hull and internode 1 phenotype.

PubMed

Hong, Lilan; Qian, Qian; Tang, Ding; Wang, Kejian; Li, Ming; Cheng, Zhukuan

2012-07-01

The biosynthesis of flavonoids, important secondary plant metabolites, has been investigated extensively, but few mutants of genes in this pathway have been identified in rice (Oryza sativa). The rice gold hull and internode (gh) mutants exhibit a reddish-brown pigmentation in the hull and internode and their phenotype has long been used as a morphological marker trait for breeding and genetic study. Here, we characterized that the gh1 mutant was a mutant of the rice chalcone isomerase gene (OsCHI). The result showed that gh1 had a Dasheng retrotransposon inserted in the 5′ UTR of the OsCHI gene, which resulted in the complete loss of OsCHI expression. gh1 exhibited golden pigmentation in hulls and internodes once the panicles were exposed to light. The total flavonoid content in gh1 hulls was increased threefold compared to wild type. Consistent with the gh1 phenotype, OsCHI transcripts were expressed in most tissues of rice and most abundantly in internodes. It was also expressed at high levels in panicles before heading, distributed mainly in lemmas and paleae, but its expression decreased substantially after the panicles emerged from the sheath. OsCHI encodes a protein functionally and structurally conserved to chalcone isomerases in other species. Our findings demonstrated that the OsCHI gene was indispensable for flux of the flavonoid pathway in rice.

Diprenylated chalcones and other constituents from the twigs of Dorstenia barteri var. subtriangularis.

PubMed

Ngameni, Barthelemy; Ngadjui, Bonaventure T; Folefoc, Gabriel N; Watchueng, Jean; Abegaz, Berhanu M

2004-02-01

The twigs of Dorstenia barteri var. subtriangularis yielded three diprenylated chalcones: (-)-3-(3,3-dimethylallyl)-5'-(2-hydroxy-3-methylbut-3-enyl)-4,2',4'-trihydroxychalcone, (+)-3-(3,3-dimethylallyl)-4',5'-[2'''-(1-hydroxy-1-methylethyl)-dihydrofurano]-4,2'-dihydroxychalcone and 3,4-(6",6"-dimethyldihydropyrano)-4',5'-[2''',-(1-hydroxy-1-methylethyl)-dihydrofurano]-2'-hydroxychalcone for which the names bartericins A, B and C, respectively, are proposed. Stipulin, beta-sitosterol and its 3-beta-D-glucopyranosyl derivative were also isolated. The structures of these secondary metabolites were determined on the basis of spectroscopic analysis, especially, NMR spectra in conjunction with 2D experiments, COSY, HMQC and HMBC. The structural relationship of bartericins B and C was further established by the chemical cyclization of one to the other.

The 2',4'-dihydroxychalcone could be explored to develop new inhibitors against the glycerol-3-phosphate dehydrogenase from Leishmania species.

PubMed

Passalacqua, Thais G; Torres, Fábio A E; Nogueira, Camila T; de Almeida, Leticia; Del Cistia, Mayara L; dos Santos, Mariana B; Dutra, Luis A; Bolzani, Vanderlan da Silva; Regasini, Luis O; Graminha, Márcia A S; Marchetto, Reinaldo; Zottis, Aderson

2015-09-01

The enzyme glycerol-3-phosphate dehydrogenase (G3PDH) from Leishmania species is considered as an attractive target to design new antileishmanial drugs and a previous in silico study reported on the importance of chalcones to achieve its inhibition. Here, we report the identification of a synthetic chalcone in our in vitro assays with promastigote cells from Leishmania amazonensis, its biological activity in animal models, and docking followed by molecular dynamics simulation to investigate the molecular interactions and structural patterns that are crucial to achieve the inhibition complex between this compound and G3PDH. A molecular fragment of this natural product derivative can provide new inhibitors with increased potency and selectivity. Copyright © 2015 Elsevier Ltd. All rights reserved.

Simple Syntheses of Two New Benzo-Fused Macrocycles Incorporating Chalcone Moiety

PubMed Central

Mondal, Rina; Samanta, Swati; Sarkar, Saheli; Mallik, Asok K.

2014-01-01

Simple syntheses of the benzo-fused 26-membered macrocyclic bischalcone (19E,43E)-2.11.27.36-tetroxaheptacyclo[44.4.0.04,9.012,17.021,26.029,34.037,42]pentaconta-1(46),4(9),5,7,12(17),13,15,19,21,23,25,29,31,33,37,39,41,43,47,49-icosaene-18,45-dione (3) and the benzo-fused 13-membered macrocyclic chalcone (19E)-2.11-dioxatetracyclo[19.4.0.04,9.012,17]pentacosa-1(25),4(9),5,7,12(17),13,15,19,21,23-decaen-18-one (5) using very common starting materials and reagents are described. The compounds are new and they have been characterized from their analytical and spectral data. PMID:27379283

Simple Syntheses of Two New Benzo-Fused Macrocycles Incorporating Chalcone Moiety.

PubMed

Mondal, Rina; Samanta, Swati; Sarkar, Saheli; Mallik, Asok K

2014-01-01

Simple syntheses of the benzo-fused 26-membered macrocyclic bischalcone (19E,43E)-2.11.27.36-tetroxaheptacyclo[44.4.0.0(4,9).0(12,17).0(21,26).0(29,34).0(37,42)]pentaconta-1(46),4(9),5,7,12(17),13,15,19,21,23,25,29,31,33,37,39,41,43,47,49-icosaene-18,45-dione (3) and the benzo-fused 13-membered macrocyclic chalcone (19E)-2.11-dioxatetracyclo[19.4.0.0(4,9).0(12,17)]pentacosa-1(25),4(9),5,7,12(17),13,15,19,21,23-decaen-18-one (5) using very common starting materials and reagents are described. The compounds are new and they have been characterized from their analytical and spectral data.

Pinostrobin Derivatives from PrenylationReaction and their Antibacterial Activity against Clinical Bacteria

NASA Astrophysics Data System (ADS)

Marliyana, S. D.; Mujahidin, D.; Syah, Y. M.

2018-04-01

Kaempferia pandurata (syn. Boesenbergia rotunda, B. pandurata (Roxb.)Schltr), locally known as "TemuKunci"in Indonesia, is one of the medicinal plants of the family Zingiberaceae. Phytochemical studies on the rhizome of K. pandurata showed the presence of flavonoid derivative, namely flavanones, which constitute as the main components of this plant. Bioactivity studies on this species exhibited various biological activities, such as antibacteria, anti-inflammatory, antitumor, antidiarrhea, antidisentri, anti-HIV, antioxidant, antipyretic, analgesic and insecticides. Among the biological activities, the antibacterial activity results are important as an attempt to answer the emergence of resistance of some bacteria against existing drugs, as well as the emergence of a number of outbreaks of disease caused by bacteria. Therefore, a search to find new compounds that are potential as an antibacterial is an urgent matter. The present study was aimed at the chemical transformation of pinostrobin (1) from K. pandurata rhizome and an antibacterial activity.The chemical transformation was performed through a prenylation reaction of pinostrobin (1) which is the main component of K. pandurata rhizome. The prenylation reaction was carried out by reacting pinostrobin (1) with prenyl bromide and potassium carbonat (K2CO3). The purification of product was done using the radial chromatography with mix solvent n-hexane and ethyl acetate (97.5:2.5; 9.5:0.5; 9.0:1.0.; 8.0:2.0). The purity test of isolated compound was analysedby TLC using different types of eluent. The identification of compounds was determined based on NMR data and mass spectra analysis. Five compounds were obtained from the prenylation reaction, i.e. monooxyprenylated pinostrobin (2), monooxyprenylated chalcone (3), diprenylated chalcone (4), triprenylated chalcone (5), and triprenylated cyclohexene chalcone (6). These compounds were tested for antibacterial activities against four clinical bacteria, namely Bacillus subtilis, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. The antibacterial test was conducted using microdilution method. The five compounds showed moderate antibacterial activity against clinical bacteria with MIC values in the range of 25 to 50 µg/mL.

Cardamonin, a schistosomicidal chalcone from Piper aduncum L. (Piperaceae) that inhibits Schistosoma mansoni ATP diphosphohydrolase.

PubMed

de Castro, Clarissa C B; Costa, Poliana S; Laktin, Gisele T; de Carvalho, Paulo H D; Geraldo, Reinaldo B; de Moraes, Josué; Pinto, Pedro L S; Couri, Mara R C; Pinto, Priscila de F; Da Silva Filho, Ademar A

2015-09-15

Schistosomiasis is one of the world's major public health problems, and praziquantel (PZQ) is the only available drug to treat this neglected disease with an urgent demand for new drugs. Recent studies indicated that extracts from Piper aduncum L. (Piperaceae) are active against adult worms of Schistosoma mansoni, the major etiological agent of human schistosomiasis. We investigated the in vitro schistosomicidal activity of cardamonin, a chalcone isolated from the crude extract of P. aduncum. Also, this present work describes, for the first time, the S. mansoni ATP diphosphohydrolase inhibitory activity of cardamonin, as well as, its molecular docking with S. mansoni ATPDase1, in order to investigate its mode of inhibition. In vitro schistosomicidal assays and confocal laser scanning microscopy were used to evaluate the effects of cardamonin on adult schistosomes. Cell viability was measured by MTT assay, and the S. mansoni ATPase activity was determined spectrophotometrically. Identification of the cardamonin binding site and its interactions on S. mansoni ATPDase1 were made by molecular docking experiments. A bioguided fractionation of the crude extract of P. aduncum was carried out, leading to identification of cardamonin as the active compound, along with pinocembrin and uvangoletin. Cardamonin (25, 50, and 100 µM) caused 100% mortality, tegumental alterations, and reduction of oviposition and motor activity of all adult worms of S. mansoni, without affecting mammalian cells. Confocal laser scanning microscopy showed tegumental morphological alterations and changes on the numbers of tubercles of S. mansoni worms in a dose-dependent manner. Cardamonin also inhibited S. mansoni ATP diphosphohydrolase (IC50 of 23.54 µM). Molecular docking studies revealed that cardamonin interacts with the Nucleotide-Binding of SmATPDase 1. The nature of SmATPDase 1-cardamonin interactions is mainly hydrophobic and hydrogen bonding. This report provides evidence for the in vitro schistosomicidal activity of cardamonin and demonstrated, for the first time, that this chalcone is highly effective in inhibiting S. mansoni ATP diphosphohydrolase, opening the route to further studies of chalcones as prototypes for new S. mansoni ATP diphosphohydrolase inhibitors. Copyright © 2015. Published by Elsevier GmbH.

Glutathione and fungal elicitor regulation of a plant defense gene promoter in electroporated protoplasts

PubMed Central

Dron, Michel; Clouse, Steven D.; Dixon, Richard A.; Lawton, Michael A.; Lamb, Christopher J.

1988-01-01

To investigate the mechanisms underlying activation of plant defenses against microbial attack we have studied elicitor regulation of a chimeric gene comprising the 5′ flanking region of a defense gene encoding the phytoalexin biosynthetic enzyme chalcone synthase fused to a bacterial chloramphenicol acetyltransferase gene. Glutathione or fungal elicitor caused a rapid, marked but transient expression of the chimeric gene electroporated into soybean protoplasts. The response closely resembled that of endogenous chalcone synthase genes in suspension cultured cells. Functional analysis of 5′ deletions suggests that promoter activity is determined by an elicitor-regulated activator located between the “TATA box” and nucleotide position -173 and an upstream silencer between -173 and -326. These cis-acting elements function in the transduction of the elicitation signal to initiate elaboration of an inducible defense response. Images PMID:16593981

Syntheses and in Vitro Antiplasmodial Activity of Aminoalkylated Chalcones and Analogues.

PubMed

Wilhelm, Anke; Kendrekar, Pravin; Noreljaleel, Anwar E M; Abay, Efrem T; Bonnet, Susan L; Wiesner, Lubbe; de Kock, Carmen; Swart, Kenneth J; van der Westhuizen, Jan Hendrik

2015-08-28

A series of readily synthesized and inexpensive aminoalkylated chalcones and diarylpropane analogues (1-55) were synthesized and tested against chloroquinone-sensitive (D10 and NF54) and -resistant (Dd2 and K1) strains of Plasmodium falciparum. Hydrogenation of the enone to a diarylpropane moiety increased antiplasmodial bioactivity significantly. The influence of the structure of the amine moiety, A-ring substituents, propyl vs ethyl linker, and chloride salt formation on further enhancing antiplasmodial activity was investigated. Several compounds have IC₅₀ values similar to or better than chloroquine (CQ). The most active compound (26) had an IC₅₀ value of 0.01 μM. No signs of resistance were detected, as can be expected from compounds with structures unrelated to CQ and other currently used antimalarial drugs. Toxicity tests (in vitro CHO cell assay) gave high SI indices.

Structure-Activity Relationship of Dialkoxychalcones to Combat Fish Pathogen Saprolegnia australis.

PubMed

Montenegro, Iván; Muñoz, Ociel; Villena, Joan; Werner, Enrique; Mellado, Marco; Ramírez, Ingrid; Caro, Nelson; Flores, Susana; Madrid, Alejandro

2018-06-07

To investigate the anti- Saprolegnia activities of chalconic compounds, nine dialkoxychalcones 2 ⁻ 10 , along with their key building block 2',4'-dihydroxychalcone 1 , were evaluated for their potential oomycide activities against Saprolegnia australis strains. The synthesis afforded a series of O -alkylated derivatives with typical chalcone skeletons. Compounds 4 ⁻ 10 were reported for the first time. Interestingly, analogue 8 with the new scaffold demonstrated remarkable in vitro growth-inhibitory activities against Saprolegnia strains, displaying greater anti-oomycete potency than the standard drugs used in the assay, namely fluconazole and bronopol. In contrast, a dramatic loss of activity was observed for O -alkylated derivatives 2 , 3 , 6 , and 7 . These findings have highlighted the therapeutic potential of the natural compound 1 scaffold to be exploitable as a drug lead with specific activity against various Saprolegnia strains.

Design, synthesis, biological evaluation, and molecular modeling studies of chalcone-rivastigmine hybrids as cholinesterase inhibitors.

PubMed

Wang, Ling; Wang, Yu; Tian, Yiguang; Shang, Jinling; Sun, Xiaoou; Chen, Hongzhuan; Wang, Hao; Tan, Wen

2017-01-01

A series of novel chalcone-rivastigmine hybrids were designed, synthesized, and tested in vitro for their ability to inhibit human acetylcholinesterase and butyrylcholinesterase. Most of the target compounds showed hBChE selective activity in the micro- and submicromolar ranges. The most potent compound 3 exhibited comparable IC 50 to the commercially available drug (rivastigmine). To better understand their structure activity relationships (SAR) and mechanisms of enzyme-inhibitor interactions, kinetic and molecular modeling studies including molecular docking and molecular dynamics (MD) simulations were carried out. Furthermore, compound 3 blocks the formation of reactive oxygen species (ROS) in SH-SY5Y cells and shows the required druggability and low cytotoxicity, suggesting this hybrid is a promising multifunctional drug candidate for Alzheimer's disease (AD) treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Medicinal flowers. XXVII. New flavanone and chalcone glycosides, arenariumosides I, II, III, and IV, and tumor necrosis factor-alpha inhibitors from everlasting, flowers of Helichrysum arenarium.

PubMed

Morikawa, Toshio; Wang, Li-Bo; Nakamura, Seikou; Ninomiya, Kiyofumi; Yokoyama, Eri; Matsuda, Hisashi; Muraoka, Osamu; Wu, Li-Jun; Yoshikawa, Masayuki

2009-04-01

The methanolic extract from the flowers of Helichrysum arenarium L. MOENCH was found to show inhibitory effect on tumor necrosis factor-alpha (TNF-alpha, 1 ng/ml)-induced cytotoxicity in L929 cells. From the methanolic extract, 50 constituents including four new flavanone and chalcone glycosides named arenariumosides I (1), II (2), III (3), and IV (4) were isolated. The stereostructures of 1-4 were elucidated on the basis of chemical and physicochemical evidence. Among the constituents, naringenin 7-O-beta-D-glucopyranoside (7), apigenin 7-O-beta-D-glucopyranoside (14), apigenin 7-O-gentiobioside (16), and apigenin 7,4'-di-O-beta-D-glucopyranoside (17) significantly inhibited TNF-alpha-induced cytotoxicity in L929 cells at 30 microM.

Synthesis, characterization of (3E)-1-(6-chloro-2-methyl-4-phenyl quinolin-3-Yl)-3-aryl prop-2-en-1-ones through IR, NMR, single crystal X-ray diffraction and insights into their electronic structure using DFT calculations

NASA Astrophysics Data System (ADS)

Sarveswari, S.; Srikanth, A.; Arul Murugan, N.; Vijayakumar, V.; Jasinski, Jerry P.; Beauchesne, Hanna C.; Jarvis, Ethan E.

2015-02-01

3E-1-(6-Chloro-2-methyl-4-phenylquinolin-3-yl)-3-arylprop-2-en-1-ones were synthesized and characterized by FTIR, 1H NMR, 13C NMR, HSQC, DEPT-135. In addition the compound 3E-1-(6-chloro-2-methyl-4-phenylquinolin-3-yl)-3-(2,5-dimethoxyphenyl)prop-2-en-1-one was subjected to the single crystal X-ray diffraction studies. Density functional theory calculations were carried out for this chalcone and its derivatives to investigate into their electronic structure, chemical reactivity, linear and non-linear optical properties. The structure predicted from DFT for chalcone is in good agreement with the structure from XRD measurement.

Quinoxaline-substituted chalcones as new inhibitors of breast cancer resistance protein ABCG2: polyspecificity at B-ring position

PubMed Central

Winter, Evelyn; Gozzi, Gustavo Jabor; Chiaradia-Delatorre, Louise Domeneghini; Daflon-Yunes, Nathalia; Terreux, Raphael; Gauthier, Charlotte; Mascarello, Alessandra; Leal, Paulo César; Cadena, Silvia M; Yunes, Rosendo Augusto; Nunes, Ricardo José; Creczynski-Pasa, Tania Beatriz; Di Pietro, Attilio

2014-01-01

A series of chalcones substituted by a quinoxaline unit at the B-ring were synthesized and tested as inhibitors of breast cancer resistance protein-mediated mitoxantrone efflux. These compounds appeared more efficient than analogs containing other B-ring substituents such as 2-naphthyl or 3,4-methylenedioxyphenyl while an intermediate inhibitory activity was obtained with a 1-naphthyl group. In all cases, two or three methoxy groups had to be present on the phenyl A-ring to produce a maximal inhibition. Molecular modeling indicated both electrostatic and steric positive contributions. A higher potency was observed when the 2-naphthyl or 3,4-methylenedioxyphenyl group was shifted to the A-ring and methoxy substituents were shifted to the phenyl B-ring, indicating preferences among polyspecificity of inhibition. PMID:24920885

Synthesis, characterization and calculated non-linear optical properties of two new chalcones

NASA Astrophysics Data System (ADS)

Singh, Ashok Kumar; Saxena, Gunjan; Prasad, Rajendra; Kumar, Abhinav

2012-06-01

Two new chalcones viz 3-(4-(benzyloxy)phenyl)-1-(2-hydroxyphenyl)prop-2-en-1-one (1) and 3-(4-chlorophenyl)-1-(2-hydroxyphenyl)prop-2-en-1-one (2) have been prepared and characterized by micro analyses, 1H NMR, IR, UV-Vis spectroscopy and single crystal X-ray. The first static hyperpolarizability (β) for both the compounds has been investigated by density functional theory (DFT). Also, the solvent-induced effects on the non-linear optical properties (NLO) were studied by using self-consistent reaction field (SCRF) method. As the solvent polarity increases, the β value increases monotonically. The electronic absorption bands of both 1 and 2 have been assigned by time dependent density functional theory (TD-DFT). Both the compounds displayed better non-linear optical (NLO) responses than the standard p-nitroaniline (pNA).

Palladium-Copper Catalyzed Alkyne Activation as an Entry to Multicomponent Syntheses of Heterocycles

NASA Astrophysics Data System (ADS)

Müller, Thomas J. J.

Alkynones and chalcones are of paramount importance in heterocyclic chemistry as three-carbon building blocks. In a very efficient manner, they can be easily generated by palladium-copper catalyzed reactions: ynones are formed from acid chlorides and terminal alkynes, and chalcones are synthesized in the sense of a coupling-isomerization (CI) sequence from (hetero)aryl halides and propargyl alcohols. Mild reaction conditions now open entries to sequential and consecutive transformations to heterocycles, such as furans, 3-halo furans, pyrroles, pyrazoles, substituted and annelated pyridines, annelated thiopyranones, pyridimines, meridianins, benzoheteroazepines and tetrahydro-β-carbolines, by consecutive coupling-cyclocondensation or CI-cyclocondensation sequences, as new diversity oriented routes to heterocycles. Domino reactions based upon the coupling-isomerization reaction (CIR) have been probed in the synthesis of antiparasital 2-substituted quinoline derivatives and highly luminescent spiro-benzofuranones and spiro-indolones.

Identification of chalcone-based antileishmanial agents targeting trypanothione reductase.

PubMed

Ortalli, Margherita; Ilari, Andrea; Colotti, Gianni; De Ionna, Ilenia; Battista, Theo; Bisi, Alessandra; Gobbi, Silvia; Rampa, Angela; Di Martino, Rita M C; Gentilomi, Giovanna A; Varani, Stefania; Belluti, Federica

2018-05-02

All currently used first-line and second-line drugs for the treatment of leishmaniasis exhibit several drawbacks including toxicity, high costs and route of administration. Furthermore, some drugs are associated with the emergence of drug resistance. Thus, the development of new treatments for leishmaniasis is a priority in the field of neglected tropical diseases. The present work highlights the use of natural derived products, i.e. chalcones, as potential source of antileishmanial agents. Thirty-one novel chalcone compounds have been synthesized and their activity has been evaluated against promastigotes of Leishmania donovani; 16 compounds resulted active against L. donovani in a range from 3.0 to 21.5 μM, showing low toxicity against mammalian cells. Among these molecules, 6 and 16 showed good inhibitory activity on both promastigotes and intracellular amastigotes, coupled with an high selectivity index. Furthermore, compounds 6 and 16 inhibited the promastigote growth of other leishmanial species, including L. tropica, L. major and L. infantum. Finally, 6 and 16 interacted with high affinity with trypanothione reductase (TR), an essential enzyme for the leishmanial parasite and compound 6 inhibited TR with sub-micromolar potency. Thus, the effective inhibitory activity against Leishmania, the lack of toxicity on mammalian cells and the ability to block a crucial parasite's enzyme, highlight the potential for compound 6 to be optimized as novel drug candidate against leishmaniasis. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Ground and excited state properties of high performance anthocyanidin dyes-sensitized solar cells in the basic solutions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prima, Eka Cahya; Computational Material Design and Quantum Engineering Laboratory, Engineering Physics, Institut Teknologi Bandung; International Program on Science Education, Universitas Pendidikan Indonesia

2015-09-30

The aglycones of anthocyanidin dyes were previously reported to form carbinol pseudobase, cis-chalcone, and trans-chalcone due to the basic levels. The further investigations of ground and excited state properties of the dyes were characterized using density functional theory with PCM(UFF)/B3LYP/6-31+G(d,p) level in the basic solutions. However, to the best of our knowledge, the theoretical investigation of their potential photosensitizers has never been reported before. In this paper, the theoretical photovoltaic properties sensitized by dyes have been successfully investigated including the electron injections, the ground and excited state oxidation potentials, the estimated open circuit voltages, and the light harvesting efficiencies. Themore » results prove that the electronic properties represented by dyes’ LUMO-HOMO levels will affect to the photovoltaic performances. Cis-chalcone dye is the best anthocyanidin aglycone dye with the electron injection spontaneity of −1.208 eV, the theoretical open circuit voltage of 1.781 V, and light harvesting efficiency of 56.55% due to the best HOMO-LUMO levels. Moreover, the ethanol solvent slightly contributes to the better cell performance than the water solvent dye because of the better oxidation potential stabilization in the ground state as well as in the excited state. These results are in good agreement with the known experimental report that the aglycones of anthocyanidin dyes in basic solvent are the high potential photosensitizers for dye-sensitized solar cell.« less

Chalcone-based Selective Inhibitors of a C4 Plant Key Enzyme as Novel Potential Herbicides

NASA Astrophysics Data System (ADS)

Nguyen, G. T. T.; Erlenkamp, G.; Jäck, O.; Küberl, A.; Bott, M.; Fiorani, F.; Gohlke, H.; Groth, G.

2016-06-01

Weeds are a challenge for global food production due to their rapidly evolving resistance against herbicides. We have identified chalcones as selective inhibitors of phosphoenolpyruvate carboxylase (PEPC), a key enzyme for carbon fixation and biomass increase in the C4 photosynthetic pathway of many of the world’s most damaging weeds. In contrast, many of the most important crop plants use C3 photosynthesis. Here, we show that 2‧,3‧,4‧,3,4-Pentahydroxychalcone (IC50 = 600 nM) and 2‧,3‧,4‧-Trihydroxychalcone (IC50 = 4.2 μM) are potent inhibitors of C4 PEPC but do not affect C3 PEPC at a same concentration range (selectivity factor: 15-45). Binding and modeling studies indicate that the active compounds bind at the same site as malate/aspartate, the natural feedback inhibitors of the C4 pathway. At the whole plant level, both substances showed pronounced growth-inhibitory effects on the C4 weed Amaranthus retroflexus, while there were no measurable effects on oilseed rape, a C3 plant. Growth of selected soil bacteria was not affected by these substances. Our chalcone compounds are the most potent and selective C4 PEPC inhibitors known to date. They offer a novel approach to combat C4 weeds based on a hitherto unexplored mode of allosteric inhibition of a C4 plant key enzyme.

Chalcone Based Homodimeric PET Agent, 11C-(Chal)2DEA-Me, for Beta Amyloid Imaging: Synthesis and Bioevaluation.

PubMed

Chauhan, Kanchan; Tiwari, Anjani K; Chadha, Nidhi; Kaul, Ankur; Singh, Ajai Kumar; Datta, Anupama

2018-04-02

Homodimeric chalcone based 11 C-PET radiotracer, 11 C-(Chal) 2 DEA-Me, was synthesized, and binding affinity toward beta amyloid (Aβ) was evaluated. The computational studies revealed multiple binding of the tracer at the recognition sites of Aβ fibrils. The bivalent ligand 11 C-(Chal) 2 DEA-Me displayed higher binding affinity compared to the corresponding monomer, 11 C-Chal-Me, and classical Aβ agents. The radiolabeling yield with carbon-11 was 40-55% (decay corrected) with specific activity of 65-90 GBq/μmol. A significant ( p < 0.0001) improvement in the binding affinity of 11 C-(Chal) 2 DEA-Me with synthetic Aβ42 aggregates over the monomer, 11 C-Chal-Me, demonstrates the utility of the bivalent approach. The PET imaging and biodistribution data displayed suitable brain pharmacokinetics of both ligands with higher brain uptake in the case of the bivalent ligand. Metabolite analysis of healthy ddY mouse brain homogenates exhibited high stability of the radiotracers in the brain with >93% intact tracer at 30 min post injection. Both chalcone derivatives were fluorescent in nature and demonstrated significant changes in the emission properties after binding with Aβ42. The preliminary analysis indicates high potential of 11 C-(Chal) 2 DEA-Me as in vivo Aβ42 imaging tracer and highlights the significance of the bivalent approach to achieve a higher biological response for detection of early stages of amyloidosis.

Yellow flowers generated by expression of the aurone biosynthetic pathway

PubMed Central

Ono, Eiichiro; Fukuchi-Mizutani, Masako; Nakamura, Noriko; Fukui, Yuko; Yonekura-Sakakibara, Keiko; Yamaguchi, Masaatsu; Nakayama, Toru; Tanaka, Takaharu; Kusumi, Takaaki; Tanaka, Yoshikazu

2006-01-01

Flower color is most often conferred by colored flavonoid pigments. Aurone flavonoids confer a bright yellow color on flowers such as snapdragon (Antirrhinum majus) and dahlia (Dahlia variabilis). A. majus aureusidin synthase (AmAS1) was identified as the key enzyme that catalyzes aurone biosynthesis from chalcones, but transgenic flowers overexpressing AmAS1 gene failed to produce aurones. Here, we report that chalcone 4′-O-glucosyltransferase (4′CGT) is essential for aurone biosynthesis and yellow coloration in vivo. Coexpression of the Am4′CGT and AmAS1 genes was sufficient for the accumulation of aureusidin 6-O-glucoside in transgenic flowers (Torenia hybrida). Furthermore, their coexpression combined with down-regulation of anthocyanin biosynthesis by RNA interference (RNAi) resulted in yellow flowers. An Am4′CGT-GFP chimeric protein localized in the cytoplasm, whereas the AmAS1(N1-60)-RFP chimeric protein was localized to the vacuole. We therefore conclude that chalcones are 4′-O-glucosylated in the cytoplasm, their 4′-O-glucosides transported to the vacuole, and therein enzymatically converted to aurone 6-O-glucosides. This metabolic pathway is unique among the known examples of flavonoid, including anthocyanin biosynthesis because, for all other compounds, the carbon backbone is completed before transport to the vacuole. Our findings herein not only demonstrate the biochemical basis of aurone biosynthesis but also open the way to engineering yellow flowers for major ornamental species lacking this color variant. PMID:16832053

Comparative molecular field analysis and molecular docking studies on novel aryl chalcone derivatives against an important drug target cysteine protease in Plasmodium falciparum.

PubMed

Thillainayagam, Mahalakshmi; Anbarasu, Anand; Ramaiah, Sudha

2016-08-21

The computational studies namely molecular docking simulations and Comparative Molecular Field Analysis (CoMFA) are executed on series of 52 novel aryl chalcones derivatives using Plasmodium falciparum cysteine proteases (falcipain - 2) as vital target. In the present study, the correlation between different molecular field effects namely steric and electrostatic interactions and chemical structures to the inhibitory activities of novel aryl chalcone derivatives is inferred to perceive the major structural prerequisites for the rational design and development of potent and novel lead anti-malarial compound. The apparent binding conformations of all the compounds at the active site of falcipain - 2 and the hydrogen-bond interactions which could be used to modify the inhibitory activities are identified by using Surflex-dock study. Statistically significant CoMFA model has been developed with the cross-validated correlation coefficient (q(2)) of 0.912 and the non-cross-validated correlation coefficient (r(2)) of 0.901. Standard error of estimation (SEE) of 0.210, with the optimum number of components is ten. The predictability of the derived model is examined with a test set consists of sixteen compounds and the predicted r(2) value is found to be 0.924. The docking and QSAR study results confer crucial suggestions for the optimization of novel 1,3-diphenyl-2-propen-1-one derivatives and synthesis of effective anti- malarial compounds. Copyright © 2016 Elsevier Ltd. All rights reserved.

Chalcone-based Selective Inhibitors of a C4 Plant Key Enzyme as Novel Potential Herbicides

PubMed Central

Nguyen, G. T. T.; Erlenkamp, G.; Jäck, O.; Küberl, A.; Bott, M.; Fiorani, F.; Gohlke, H.; Groth, G.

2016-01-01

Weeds are a challenge for global food production due to their rapidly evolving resistance against herbicides. We have identified chalcones as selective inhibitors of phosphoenolpyruvate carboxylase (PEPC), a key enzyme for carbon fixation and biomass increase in the C4 photosynthetic pathway of many of the world’s most damaging weeds. In contrast, many of the most important crop plants use C3 photosynthesis. Here, we show that 2′,3′,4′,3,4-Pentahydroxychalcone (IC50 = 600 nM) and 2′,3′,4′-Trihydroxychalcone (IC50 = 4.2 μM) are potent inhibitors of C4 PEPC but do not affect C3 PEPC at a same concentration range (selectivity factor: 15–45). Binding and modeling studies indicate that the active compounds bind at the same site as malate/aspartate, the natural feedback inhibitors of the C4 pathway. At the whole plant level, both substances showed pronounced growth-inhibitory effects on the C4 weed Amaranthus retroflexus, while there were no measurable effects on oilseed rape, a C3 plant. Growth of selected soil bacteria was not affected by these substances. Our chalcone compounds are the most potent and selective C4 PEPC inhibitors known to date. They offer a novel approach to combat C4 weeds based on a hitherto unexplored mode of allosteric inhibition of a C4 plant key enzyme. PMID:27263468

Design, synthesis and activity of novel sorafenib analogues bearing chalcone unit.

PubMed

Wang, Min; Xu, Shan; Wu, Chunjiang; Liu, Xiaobo; Tao, Hong; Huang, Yanli; Liu, Yongchan; Zheng, Pengwu; Zhu, Wufu

2016-11-15

Two series of sorafenib derivatives (N-methylpicolinamide-4-oxy) chalcones (5a-o, 7a-e) were synthesized and characterized by NMR and MS. All of the target compounds were evaluated for the cytotoxicity against A549, HepG2, MCF-7, and PC-3 cancer cell lines and some selected compounds were further evaluated for the activity against VEGFR-2/KDR and BRAF kinases. The results indicated that all the compounds showed moderate to good antitumor activity, and the compound 5c showed well cytotoxic activity against HepG2, MCF-7 and PC-3 cell lines with IC 50 values of 0.56±0.83μM, 3.88±1.03μM and 3.15±0.81μM, which were 1.03-6.14-fold more active than sorafenib (3.44±1.50μM, 3.18±1.43μM, 3.24±0.45μM), respectively. The compound 5b showed good activity on VEGFR-2/KDR kinase, and its IC 50 value was 0.72μM. Structure-activity relationships (SARs) and docking studies indicated that replacement of urea group of sorafenib by chalcone ketones improved the cytotoxic activity, and the results suggested that halogen [3-Br, 4-F] and methoxy (substituted on C-3,4,5 or C-2,3,4 position) substitution was benefit for the activity. Copyright © 2016 Elsevier Ltd. All rights reserved.

An In-Silico Investigation of Phytochemicals as Antiviral Agents Against Dengue Fever.

PubMed

Powers, Chelsea N; Setzer, William N

2016-01-01

A virtual screening analysis of our library of phytochemical structures with dengue virus protein targets has been carried out using a molecular docking approach. A total of 2194 plant-derived secondary metabolites have been docked. This molecule set comprised of 290 alkaloids (68 indole alkaloids, 153 isoquinoline alkaloids, 5 quinoline alkaloids, 13 piperidine alkaloids, 14 steroidal alkaloids, and 37 miscellaneous alkaloids), 678 terpenoids (47 monoterpenoids, 169 sesquiterpenoids, 265 diterpenoids, 81 steroids, and 96 triterpenoids), 20 aurones, 81 chalcones, 349 flavonoids, 120 isoflavonoids, 74 lignans, 58 stilbenoids, 169 miscellaneous polyphenolic compounds, 100 coumarins, 28 xanthones, 67 quinones, and 160 miscellaneous phytochemicals. Dengue virus protein targets examined included dengue virus protease (NS2B-NS3pro), helicase (NS3 helicase), methyltransferase (MTase), RNA-dependent RNA polymerase (RdRp), and the dengue virus envelope protein. Polyphenolic compounds, flavonoids, chalcones, and other phenolics were the most numerous of the strongly docking ligands for dengue virus protein targets.

Experimental and theoretical study on DPPH radical scavenging mechanism of some chalcone quinoline derivatives

NASA Astrophysics Data System (ADS)

Hamlaoui, Ikram; Bencheraiet, Reguia; Bensegueni, Rafik; Bencharif, Mustapha

2018-03-01

In this study, the antioxidant capacity of three chalcone derivatives was evaluated by DPPH free radical scavenging. Experimental data showed low antioxidant activity (IC50±SD) of these molecules in comparison with BHT. The mechanism of DPPH radical scavenging elucidated by means of density functional theory (DFT) calculations. The tested compounds and their corresponding radicals and anions were optimized using B3LYP functional with 6-31G (d,p) basis set in the gas phase. The C-PCM model was used to perform solvent medium calculations. On the basis of theoretical calculations, it was shown that HAT mechanism was predominant in the gas phase, whereas SET-PT and SPLET mechanisms were favored in the presence of the solvent. Moreover, the HOMO orbitals and spin density distribution was evaluated to predict the probable sites for free radical attack.

Chemically synthesized glycosides of hydroxylated flavylium ions as suitable models of anthocyanins: binding to iron ions and human serum albumin, antioxidant activity in model gastric conditions.

PubMed

Al Bittar, Sheiraz; Mora, Nathalie; Loonis, Michèle; Dangles, Olivier

2014-12-11

Polyhydroxylated flavylium ions, such as 3',4',7-trihydroxyflavylium chloride (P1) and its more water-soluble 7-O-β-d-glucopyranoside (P2), are readily accessible by chemical synthesis and suitable models of natural anthocyanins in terms of color and species distribution in aqueous solution. Owing to their catechol B-ring, they rapidly bind FeIII, weakly interact with FeII and promote its autoxidation to FeIII. Both pigments inhibit heme-induced lipid peroxidation in mildly acidic conditions (a model of postprandial oxidative stress in the stomach), the colorless (chalcone) forms being more potent than the colored forms. Finally, P1 and P2 are moderate ligands of human serum albumin (HSA), their likely carrier in the blood circulation, with chalcones having a higher affinity for HSA than the corresponding colored forms.

Separation of two major chalcones from Angelica keiskei by high-speed counter-current chromatography.

PubMed

Kil, Yun-Seo; Nam, Joo-Won; Lee, Jun; Seo, Eun Kyoung

2015-08-01

Angelica keiskei (Shin-sun cho) is an edible higher plant with the beneficial preventive effects on cancer, hypertension, and coronary heart disease. Two bioactive chalcones of Shin-sun cho, xanthoangelol (1) and 4-hydroxyderricin (2), were separated simultaneously by using high-speed counter-current chromatography with a two-phase solvent system composed of n-hexane-EtOAc-MeOH-H2O (9:5:9:4). Only nonconsuming processes, solvent fractionations and Sephadex LH-20 column chromatography, were conducted as presteps. Xanthoangelol (1, 35.9 mg, 99.9 % purity at 254 and 365 nm) and 4-hydroxyderricin (2, 4.4 mg, 98.7 % purity at 254 nm and 98.8 % purity at 365 nm) were successfully purified from 70 mg of the processed extract from A. keiskei. The structures of two compounds were confirmed by (1)H- and (13)C-NMR analysis.

Evolution of the chalcone synthase gene family in the genus Ipomoea.

PubMed Central

Durbin, M L; Learn, G H; Huttley, G A; Clegg, M T

1995-01-01

The evolution of the chalcone synthase [CHS; malonyl-CoA:4-coumaroyl-CoA malonyltransferase (cyclizing), EC 2.3.1.74] multigene family in the genus Ipomoea is explored. Thirteen CHS genes from seven Ipomoea species (family Convolvulaceae) were sequenced--three from genomic clones and the remainder from PCR amplification with primers designed from the 5' flanking region and the end of the 3' coding region of Ipomoea purpurea Roth. Analysis of the data indicates a duplication of CHS that predates the divergence of the Ipomoea species in this study. The Ipomoea CHS genes are among the most rapidly evolving of the CHS genes sequenced to date. The CHS genes in this study are most closely related to the Petunia CHS-B gene, which is also rapidly evolving and highly divergent from the rest of the Petunia CHS sequences. PMID:7724563

Prenylated chalcones, flavone and other constituents of the twigs of Dorstenia angusticornis and Dorstenia barteri var. subtriangularis.

PubMed

Ngadjui, Bonaventure T; Watchueng, Jean; Keumedjio, Felix; Ngameni, Bathélémy; Simo, Ingrid K; Abegaz, Berhanu M

2005-03-01

The twigs of Dorstenia angusticornis and Dorstenia barteri var. subtriangularis yielded 16 compounds. Two novel diprenylated chalcones: 3,5'-di-(2-hydroxy-3-methylbut-3-enyl)-4,2',4'-trihydroxychalcone, 3, 4-(2,2-dimethylpyrano)-3'-(2-hydroxy-3-methylbut-3-enyl)-2',4'-dihydroxychalcone and the known stipulin were isolated from both species. 3-(2-Hydroxy-3-methylbut-3-enyl)-5'-(3,3-dimethylallyl)-4,2',4'-trihydroxychalcone and the known compounds: 4-hydroxylonchocarpin, kanzonol B, bartericins A, B, C and 3'-(2-hydroxy -3-methylbut-3-enyl)-4,2',4'-trihydroxychalcone were isolated from D. barteri while the known compounds: gancaonin Q, paratocarpins C, F, and lupeol were obtained from Dorstenia angusticornis. beta-Sitosterol and its beta-d-glucopyranoside were isolated from both species. Structures of these secondary metabolites were established using spectroscopic analysis, especially, NMR spectra in conjunction with 2D experiments, COSY, HMQC and HMBC.

Microwave-assisted synthesis and tyrosinase inhibitory activity of chalcone derivatives.

PubMed

Liu, Jinbing; Chen, Changhong; Wu, Fengyan; Zhao, Liangzhong

2013-07-01

A series of chalcones and their derivatives were synthesized, and their inhibitory effects on the diphenolase activity of mushroom tyrosinase were evaluated. The results showed that some of the synthesized compounds exhibited significant inhibitory activity, and four compounds exhibited more potent tyrosinase inhibitory activity than the reference standard inhibitor kojic acid (5-hydroxy-2-(hydroxymethyl)-4H-pyran-4-one). Specifically, 1-(-1-(4-methoxyphen- yl)-3-phenylallylidene)thiosemicarbazide (18) exhibited the most potent tyrosinase inhibitory activity with IC₅₀ value of 0.274 μM. The inhibition mechanism analysis of 1-(-1-(2,4-dihydroxyphenyl)-3-phenylallylidene) thiosemicarbazide (16) and 1-(-1-(4-methoxyphenyl)-3-phenylallylidene) thiosemicarbazide (18) demonstrated that the inhibitory effects of the two compounds on the tyrosinase were irreversible. Preliminary structure activity relationships' analysis suggested that further development of such compounds might be of interest. © 2013 John Wiley & Sons A/S.

Efficient ultrasound-assisted synthesis, spectroscopic, crystallographic and biological investigations of pyrazole-appended quinolinyl chalcones

NASA Astrophysics Data System (ADS)

Prasath, R.; Bhavana, P.; Sarveswari, S.; Ng, Seik Weng; Tiekink, Edward R. T.

2015-02-01

Two series of new quinolinyl chalcones containing a pyrazole group, 3a-f and 4a-r, have been synthesized by Claisen-Schmidt condensation of the derivatives of 2-methyl-3-acetylquinoline with either substituted 1,3-diphenyl-1H-pyrazole-4-carbaldehyde or 5-chloro-3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde in 76-93% yield under ultrasonic method. The compounds were characterized using IR, 1H NMR and ESI-MS spectroscopic methods and, for representative compounds, by X-ray crystallography. An E-configuration about the Cdbnd C ethylene bond has been established via 1H NMR spectroscopy and X-ray crystallography. These compounds show promising anti-microbial properties, with 4a and 3e being the most potent against bacterial and fungal strains, respectively and the methoxy substituted compounds showed moderate anti-oxidant activity.

Novel quinolone chalcones targeting colchicine-binding pocket kill multidrug-resistant cancer cells by inhibiting tubulin activity and MRP1 function.

PubMed

Lindamulage, I Kalhari; Vu, Hai-Yen; Karthikeyan, Chandrabose; Knockleby, James; Lee, Yi-Fang; Trivedi, Piyush; Lee, Hoyun

2017-08-31

Agents targeting colchicine-binding pocket usually show a minimal drug-resistance issue, albeit often associated with high toxicity. Chalcone-based compounds, which may bind to colchicine-binding site, are found in many edible fruits, suggesting that they can be effective drugs with less toxicity. Therefore, we synthesized and examined 24 quinolone chalcone compounds, from which we identified ((E)-3-(3-(2-Methoxyphenyl)-3-oxoprop-1-enyl) quinolin-2(1H)-one) (CTR-17) and ((E)-6-Methoxy-3-(3-(2-methoxyphenyl)-3-oxoprop-1-enyl) quinolin-2(1H)-one) (CTR-20) as promising leads. In particular, CTR-20 was effective against 65 different cancer cell lines originated from 12 different tissues, largely in a cancer cell-specific manner. We found that both CTR-17 and CTR-20 reversibly bind to the colchicine-binding pocket on β-tubulin. Interestingly however, both the CTRs were highly effective against multidrug-resistant cancer cells while colchicine, paclitaxel and vinblastine were not. Our study with CTR-20 showed that it overcomes multidrug-resistance through its ability to impede MRP1 function while maintaining strong inhibition against microtubule activity. Data from mice engrafted with the MDA-MB-231 triple-negative breast cancer cells showed that both CTR-17 and CTR-20 possess strong anticancer activity, alone or in combination with paclitaxel, without causing any notable side effects. Together, our data demonstrates that both the CTRs can be effective and safe drugs against many different cancers, especially against multidrug-resistant tumors.

Synergistic combination of fluoro chalcone and doxorubicin on HeLa cervical cancer cells by inducing apoptosis

NASA Astrophysics Data System (ADS)

Arianingrum, Retno; Arty, Indyah Sulistyo; Atun, Sri

2017-03-01

Doxorubicin (Dox), a primary chemotherapeutic agent used for cancer treatment is known to have various side effect included multidrug resistance (MDR) phenomenon. Combination chemotherapy is one of some approaches to reduce Dox side effect. Chalcones have been reported to reduce the proliferation of many cancer cells. The research were conducted to investigate the cytotoxic activity and apoptosis induction of a chalcone derivate which is containing fluoro substituent [1 - (4" - fluorophenyl) -3 - (4' - hydroxy - 3' - methoxyphenyl) - 2 - propene - 1 -on] (FHM) and its combination with Dox on HeLa cells line. The observation of the cytotoxic activity was conducted using MTT [3 - (4, 5 - dimethyl thiazol - 2 - y1) - 2.5 - diphenyltetrazolium bromide] assay. Apoptosis induction was determined by flow cytometric. The changes of cell morphology were observed using phase contrast microscopy. The combination index (CI) was used to determine the effect of the combination. The study showed that FHM inhibited the HeLa cell growth with IC50 of 34 μM, while the IC50 of Dox was 1 μM. The combination had a higher inhibitory effect on cell growth compare to the single treatment of FHM and Dox. All of the combination doses under IC50 of FHM and Dox gave synergistic (CI: - 0.7) up to strong synergistic effect (CI: 0.l - 0.3). The synergistic effects of the combination were due to their ability to induce apoptosis in the HeLa cells. According to the result, FHM was potential to be developed as a co-chemotherapeutic agent with Dox for cervical cancer.

Synthetic chalcones as potential anti-inflammatory and cancer chemopreventive agents.

PubMed

Won, Shen-Jeu; Liu, Cheng-Tsung; Tsao, Lo-Ti; Weng, Jing-Ru; Ko, Horng-Huey; Wang, Jih-Pyang; Lin, Chun-Nan

2005-01-01

In an effort to develop potent anti-inflammatory and cancer chemopreventive agents, a series of chalcones were prepared by Claisen-Schmidt condensation of appropriate acetophenones with suitable aromatic aldehyde or prepared with appropriate dihydrochalcone reacted with appropriate alkyl bromide or prepared in one-pot procedure involving acetophenone and convenient aromatic aldehyde using ultrasonic agitation on basic alumina. The synthesized products were tested for their inhibitory effects on the activation of mast cells, neutrophils, macrophages, and microglial cells. The potent inhibitors of NO production in macrophages and microglial cells were further evaluated for their in vitro cytotoxic effects against several human cancer cell lines. 2'-Hydroxychalcones 1-3, and 2',5'-dihydroxychalcone 7 exhibited potent inhibitory effects on the release of beta-glucuronidase or lysozyme from rat neutrophils stimulated with formyl-Met-Leu-Phe (fMLP)/cytochalasin B (CB). Two 2'-hydroxychalcones (1 and 3) showed potent inhibitory effects on superoxide anion generation in rat neutrophils in response to fMLP/CB. The previously reported chalcone, 5, 6, and 12, exhibited potent inhibitory effect on NO production in lipopolysaccharide (LPS)/interferon-gamma (IFN-gamma)-activated N9 microglial cells or in LPS-activated RAW 264.7 macrophage-like cells. The potent inhibitors 5, 6, and 12 of NO production in macrophages or microglial cells revealed significant or marginal cytotoxic effects against several human cancer lines. Compound 12 manifested potent selective cytotoxicity against human MCF-7 cells and caused cell death by apoptosis. The present results demonstrated that 1-3, and 7 have anti-inflammatory effects and 5, 6, and 12 are potential anti-inflammatory and cancer chemopreventive agents.

Synthesis, characterization and biological evaluation of novel chalcone sulfonamide hybrids as potent intestinal alkaline phosphatase inhibitors.

PubMed

Ejaz, Syeda Abida; Saeed, Aamer; Siddique, Muhammad Nasir; Nisa, Zaib Un; Khan, Samiullah; Lecka, Joanna; Sévigny, Jean; Iqbal, Jamshed

2017-02-01

Alkaline phosphatase (AP) and ecto-5'-nucleotidase (e5'NT) belong to same family that hydrolyze the extracellular nucleotides and ensure the bioavailability of nucleotides and nucleosides at purinergic receptors. During pathophysiological conditions, the over expression of AP and e5'NT lead to an increased production of adenosine that enhance tumor proliferation, invasiveness, neoangiogenesis and disrupts the body antitumor response. As both enzymes are abundantly expressed in above mentioned conditions, therefore it is of great interest to synthesize and develop potent inhibitors of these enzymes that augment the antitumor therapy. Herein we reported the synthesis and biological activity of a new series of chalcone-sulfonamide hybrids (4a-j). These derivatives were then evaluated for their inhibitory potential against two members of ecto-nucleotidase family, e5'NT (human and rat) and APs isozyme (intestinal and tissue nonspecific). Only six derivatives were found to inhibit both human and rat e5'NT enzymes. Compounds 4e and 4d showed maximum inhibition of human and rat e5'NT with an IC 50 ±SEM=0.26±0.01 and 0.33±0.004μM, respectively. Moreover, on APs, these derivatives were identified as the selective inhibitors of calf intestinal AP (c-IAP). The derivative 4a exhibited maximum inhibition of c-IAP with an IC 50 ±SEM=0.12±0.02μM. In conclusion, these chalcone-sulfonamide hybrids exhibited dual inhibition of both family of isozymes but was more selective towards c-IAP enzyme. Copyright © 2017 Elsevier Inc. All rights reserved.

The place of Ruscus extract, hesperidin methyl chalcone, and vitamin C in the management of chronic venous disease.

PubMed

Jawien, Arkadiusz; Bouskela, Eliete; Allaert, François A; Nicolaïdes, Andrew N

2017-02-01

Despite continuous improvement in our knowledge and management of chronic venous disease (CVD), certain areas, such as the role of muscarinic receptors in the pathology and treatment of CVD, remain unexplored. The symposium "The place of Ruscus extract, hesperidin methyl chalcone, and vitamin C in the management of CVD", held at the Annual Meeting of the European Venous Forum on 7-9 July 2016 in London, presented an update on the pathophysiology of CVD and highlighted how the combination of Ruscus extract, hesperidin methyl chalcone, and vitamin C (Ruscus/HMC/VitC; Cyclo 3® Fort), may counteract the deleterious processes underlying CVD. The data presented during this symposium are reported here. The pathophysiology of CVD is driven by a complex process involving numerous factors, with the two key players being venous hypertension and the inflammatory response. The cascade of reactions induced by disturbed venous flow, inflammation, and tissue alterations results in the early appearance of symptoms and progressive development of clinical signs of disease. Previous studies have shown that Ruscus extract acts at three levels: on the veins, capillaries and lymphatics, and has anti-inflammatory properties. A series of recent experiments has shed new light on the mechanism of action of the combination of Ruscus/HMC/VitC. The efficacy of Ruscus/HMC/VitC in CVD is supported by clinical studies, while two meta-analyses have confirmed a significant decrease of several symptoms and ankle circumference in response to treatment with this agent, leading to the conclusion that Ruscus/HMC/VitC deserves a Grade A rating.

Role of hydrogen bonds in the reaction mechanism of chalcone isomerase.

PubMed

Jez, Joseph M; Bowman, Marianne E; Noel, Joseph P

2002-04-23

In flavonoid, isoflavonoid, and anthocyanin biosynthesis, chalcone isomerase (CHI) catalyzes the intramolecular cyclization of chalcones into (S)-flavanones with a second-order rate constant that approaches the diffusion-controlled limit. The three-dimensional structures of alfalfa CHI complexed with different flavanones indicate that two sets of hydrogen bonds may possess critical roles in catalysis. The first set of interactions includes two conserved amino acids (Thr48 and Tyr106) that mediate a hydrogen bond network with two active site water molecules. The second set of hydrogen bonds occurs between the flavanone 7-hydroxyl group and two active site residues (Asn113 and Thr190). Comparison of the steady-state kinetic parameters of wild-type and mutant CHIs demonstrates that efficient cyclization of various chalcones into their respective flavanones requires both sets of contacts. For example, the T48A, T48S, Y106F, N113A, and T190A mutants exhibit 1550-, 3-, 30-, 7-, and 6-fold reductions in k(cat) and 2-3-fold changes in K(m) with 4,2',4'-trihydroxychalcone as a substrate. Kinetic comparisons of the pH-dependence of the reactions catalyzed by wild-type and mutant enzymes indicate that the active site hydrogen bonds contributed by these four residues do not significantly alter the pK(a) of the intramolecular cyclization reaction. Determinations of solvent kinetic isotope and solvent viscosity effects for wild-type and mutant enzymes reveal a change from a diffusion-controlled reaction to one limited by chemistry in the T48A and Y106F mutants. The X-ray crystal structures of the T48A and Y106F mutants support the assertion that the observed kinetic effects result from the loss of key hydrogen bonds at the CHI active site. Our results are consistent with a reaction mechanism for CHI in which Thr48 polarizes the ketone of the substrate and Tyr106 stabilizes a key catalytic water molecule. Hydrogen bonds contributed by Asn113 and Thr190 provide additional stabilization in the transition state. Conservation of these residues in CHIs from other plant species implies a common reaction mechanism for enzyme-catalyzed flavanone formation in all plants.

HIGHLY DIASTEREOSELECTIVE MICHAEL REACTION UNDER SOLVENT-FREE CONDITIONS USING MICROWAVES: CONJUGATE ADDITION OF FLAVANONE TO ITS CHALCONE PRECURSOR

EPA Science Inventory

Microwave-assisted reaction of 2'-hydroxychalcones in the presence of DBU resulted in the formation of hitherto unknown dimers by conjugate addition of the intermediate cyclic ketone to the starting enone.

Structural characterizations, Hirshfeld surface analyses, and third-order nonlinear optical properties of two novel chalcone derivatives

NASA Astrophysics Data System (ADS)

Maidur, Shivaraj R.; Jahagirdar, Jitendra R.; Patil, Parutagouda Shankaragouda; Chia, Tze Shyang; Quah, Ching Kheng

2018-01-01

We report synthesis, characterizations, structure-property relationships, and third-order nonlinear optical studies for two new chalcone derivatives, (2E)-1-(anthracen-9-yl)-3-(4-bromophenyl)prop-2-en-1-one (Br-ANC) and (2E)-1-(anthracen-9-yl)-3-(4-chlorophenyl)prop-2-en-1-one (Cl-ANC). These derivatives were crystallized in the centrosymmetric monoclinic P21/c crystal structure. The intermolecular interactions of both the crystals were visualized by Hirshfeld surface analyses (HSA). The crystals are thermally stable up to their melting points (180.82 and 191.16 °C for Cl-ANC and Br-ANC, respectively). The geometry optimizations, FT-IR spectra, 1H and 13C NMR spectra, electronic absorption spectra, electronic transitions, and HOMO-LUMO energy gaps were studied by Density Functional Theory (DFT) at B3LYP/6-311+G(d, p) level. The theoretical results provide excellent agreement with experimental findings. The electric dipole moments, static polarizabilities, molecular electrostatic potentials (MEP) and global chemical reactivity descriptors (GCRD) were also theoretically computed. The materials exhibited good nonlinear absorption (NLA), nonlinear refraction (NLR) and optical limiting (OL) behavior under diode-pumped solid-state (DPSS) continuous wave (CW) laser excitation (532 nm and 200 mW). The NLO parameters such as NLA coefficient (β∼10-5 cmW-1), NLR index (n2∼10-10 cm2 W-1) and third-order NLO susceptibilities (χ(3) ∼10-7 esu) were measured. Further, we estimated one-photon and two-photon figures of merit, which satisfy the demands (W > 1 and T < 1) for all-optical switching. Thus, the present chalcone derivatives with anthracene moiety are potential materials for OL and optical switching applications.

Inhibition of interleukin-3- and interferon- α-induced JAK/STAT signaling by the synthetic α-X-2',3,4,4'-tetramethoxychalcones α-Br-TMC and α-CF3-TMC.

PubMed

Jobst, Belinda; Weigl, Julia; Michl, Carina; Vivarelli, Fabio; Pinz, Sophia; Amslinger, Sabine; Rascle, Anne

2016-11-01

The JAK/STAT pathway is an essential mediator of cytokine signaling, often upregulated in human diseases and therefore recognized as a relevant therapeutic target. We previously identified the synthetic chalcone α-bromo-2',3,4,4'-tetramethoxychalcone (α-Br-TMC) as a novel JAK2/STAT5 inhibitor. We also found that treatment with α-Br-TMC resulted in a downward shift of STAT5 proteins in SDS-PAGE, suggesting a post-translational modification that might affect STAT5 function. In the present study, we show that a single cysteine within STAT5 is responsible for the α-Br-TMC-induced protein shift, and that this modification does not alter STAT5 transcriptional activity. We also compared the inhibitory activity of α-Br-TMC to that of another synthetic chalcone, α-trifluoromethyl-2',3,4,4'-tetramethoxychalcone (α-CF3-TMC). We found that, like α-Br-TMC, α-CF3-TMC inhibits JAK2 and STAT5 phosphorylation in response to interleukin-3, however without altering STAT5 mobility in SDS-PAGE. Moreover, we demonstrate that both α-Br-TMC and α-CF3-TMC inhibit interferon-α-induced activation of STAT1 and STAT2, by inhibiting their phosphorylation and the expression of downstream interferon-stimulated genes. Together with the previous finding that α-Br-TMC and α-CF3-TMC inhibit the response to inflammation by inducing Nrf2 and blocking NF-κB activities, our data suggest that synthetic chalcones might be useful as anti-inflammatory, anti-cancer and immunomodulatory agents in the treatment of human diseases.

Three closely related 1-(naphthalen-2-yl)prop-2-en-1-ones: pseudosymmetry, disorder and supramoleular assembly mediated by C-H...π and C-Br...π interactions.

PubMed

Girisha, Marisiddaiah; Sagar, Belakavadi K; Yathirajan, Hemmige S; Rathore, Ravindranath S; Glidewell, Christopher

2017-02-01

It has been observed that when electron-rich naphthyl rings are present in chalcones they can participate in π-π stacking interactions, and this can play an important role in orientating inhibitors within the active sites of enzymes, while chalcones containing heterocyclic substituents additionally exhibit fungistatic and fungicidal properties. With these considerations in mind, three new chalcones containing 2-naphthyl substituents were prepared. 3-(4-Fluorophenyl)-1-(naphthalen-2-yl)prop-2-en-1-one, C 19 H 13 FO, (I), crystallizes with Z' = 2 in the space group P-1 and the four molecules in the unit cell adopt an arrangement which resembles that in the space group P2 1 /a. Although 3-(4-bromophenyl)-1-(naphthalen-2-yl)prop-2-en-1-one, C 19 H 13 BrO, (II), with Z' = 1, is not isostructural with (I), the molecules of (I) and (II) adopt very similar conformations. In 1-(naphthalen-2-yl)-3-(thiophen-2-yl)prop-2-en-1-one, C 17 H 12 OS, (III), the thiophene unit is disordered over two sets of atomic sites, with occupancies of 0.780 (3) and 0.220 (3), which are related by a near 180° rotation of the thiophene unit about its exocyclic C-C bond. The molecules of compound (I) are linked by three independent C-H...π(arene) hydrogen bonds to form centrosymmetric octamolecular aggregates, whereas the molecules of compound (II) are linked into molecular ladders by a combination of C-H...π(arene) and C-Br...π(arene) interactions, and those of compound (III) are linked into centrosymmetric dimers by C-H...π(thiophene) interactions.

Ultraviolet irradiation induces accumulation of isoflavonoids and transcription of genes of enzymes involved in the calycosin-7-O-β-d-glucoside pathway in Astragalus membranaceus Bge. var. mongholicus (Bge.) Hsiao.

PubMed

Xu, Rong-Yan; Nan, Peng; Yang, Yixin; Pan, Haiyun; Zhou, Tongshui; Chen, Jiakuan

2011-07-01

Isoflavonoids are a group of phenolic secondary metabolites found almost exclusively in leguminous plants. Formononetin, calycosin and calycosin-7-O-β-d-glucoside (CG) are isoflavonoid products in the CG pathway. Accumulation of the three isoflavonoids plus daidzein and expression of six genes of enzymes involved in the CG pathway were studied in Astragalus membranaceus Bge. var. mongholicus (Bge.) Hsiao with ultraviolet (UV) irradiation. Our results showed that (1) main isoflavonoids in roots, stems and leaves were CG, daidzein and calycosin, respectively; they accumulated significantly under the induction of UV irradiation during 8 days but their content declined later; (2) expression of six genes of enzymes involved in the CG pathway was inhibited slightly at early stage but the expression was increased greatly afterward; (3) chalcone synthase, chalcone reductase and chalcone isomerase were expressed to their individual maximum level within shorter hours than were cinnamate 4-hydroxylase, isoflavone synthase (IFS) and isoflavone 3'-hydroxylase and (4) more calycosin but less daidzein accumulated in leaves. IFS was highly expressed in leaves, which might lead to high accumulation of the common precursor of daidzein and 2,7-dihydroxy-4'-O-methoxy-isoflavanone, the latter of which would be converted to formononetin, calycosin and CG via a series of reactions. Little daidzein accumulated in leaves, which suggested that rather than be converted to daidzein, the 2,7,4'-trihydroxyisoflavanone was probably more easily caught by 2-hydroxyisoflavanone 4'-O-methyltransferase and hence provided more precursors for formononetin. The findings were discussed in terms of the influence of UV irradiation in the accumulation of isoflavonoids. Copyright © Physiologia Plantarum 2011.

A Computational Model for Docking of Noncompetitive Neuraminidase Inhibitors and Probing their Binding Interactions with Neuraminidase of Influenza Virus H5N1.

PubMed

Chintakrindi, Anand S; Martis, Elvis A F; Gohil, Devanshi J; Kothari, Sweta T; Chowdhary, Abhay S; Coutinho, Evans C; Kanyalkar, Meena A

2016-01-01

With cases of emergence of drug resistance to the current competitive inhibitors of neuraminidase (NA) such as oseltamivir and zanamavir, there is a present need for an alternative approach in the treatment of avian influenza. With this in view, some flavones and chalcones were designed based on quercetin, the most active naturally occurring noncompetitive inhibitor. We attempt to understand the binding of quercetin to H5N1-NA, and synthetic analogs of quercetin namely flavones and its precursors the chalcones using computational tools. Molecular docking was done using Libdock. Molecular dynamics (MD) simulations were performed using Amber14. We synthesized the two compounds; their structures were confirmed by infrared spectroscopy, 1H-NMR, and mass spectrometry. These molecules were then tested for H5N1-NA inhibition and kinetics of inhibition. Molecular docking studies yielded two compounds i.e., 4'-methoxyflavone and 2'-hydroxy-4-methoxychalcone, as promising leads which identified them as binders of the 150-cavity of NA. Furthermore, MD simulation studies revealed that quercetin and the two compounds bind and hold the 150 loop in its open conformation, which ultimately perturbs the binding of sialic acid in the catalytic site. Estimation of the free energy of binding by MM-PBSA portrays quercetin as more potent than chalcone and flavone. These molecules were then determined as non-competitive inhibitors from the Lineweaver-Burk plots rendered from the enzyme kinetic studies. We conclude that non-competitive type of inhibition, as shown in this study, can serve as an effective method to block NA and evade the currently seen drug resistance.

Structural and vibrational characteristics of a non-linear optical material 3-(4-nitrophenyl)-1-(pyridine-3-yl) prop-2-en-1-one probed by quantum chemical computation and spectroscopic techniques

NASA Astrophysics Data System (ADS)

Kumar, Ram; Karthick, T.; Tandon, Poonam; Agarwal, Parag; Menezes, Anthoni Praveen; Jayarama, A.

2018-07-01

Chalcone and its derivatives are well-known for their high non-linear optical behavior and charge transfer characteristics. The effectiveness of charge transfer via ethylenic group and increase in NLO response of the chalcone upon substitutions are of great interest. The present study focuses the structural, charge transfer and non-linear optical properties of a new chalcone derivative "3-(4-nitrophenyl)-1-(pyridine-3-yl) prop-2-en-1-one" (hereafter abbreviated as 4 NP3AP). To accomplish this task, we have incorporated the experimental FT-IR, FT-Raman and UV-vis spectroscopic studies along with quantum chemical calculations. The frequency assignments of peaks in IR and Raman have been done on the basis of potential energy distribution and the results were compared with the earlier reports on similar kind of molecules. For obtaining the electronic transition details of 4 NP3AP, UV-vis spectrum has been simulated by considering both gaseous and solvent phase using time-dependent density functional theory (TD-DFT). The HOMO-LUMO energy gap, most important factor to be considered for studying charge transfer properties of the molecule has been calculated. The electron density surface map corresponding to the net electrostatic point charges has been generated to obtain the electrophilic and nucleophilic sites. The charge transfer originating from the occupied (donor) and unoccupied (acceptor) molecular orbitals have been analyzed with the help of natural bond orbital theory. Moreover, the estimation of second-hyperpolarizability of the molecule confirms the non-linear optical behavior of the molecule.

Induction of Anthocyanin Accumulation by Cytokinins in Arabidopsis thaliana.

PubMed Central

Deikman, J.; Hammer, P. E.

1995-01-01

Arabidopsis thaliana plants treated with exogenous cytokinins accumulate anthocyanin pigments. We have characterized this response because it is potentially useful as a genetic marker for cytokinin responsiveness. Levels of mRNAs for four genes of the anthocyanin biosynthesis pathway, phenylalanine ammonia lyase 1 (PAL1), chalcone synthase (CHS), chalcone isomerase (CHI), and dihydroflavonol reductase (DFR) were shown to increase coordinately in response to benzyladenine (BA). However, nuclear run-on transcription experiments suggested that although CHS and DFR are controlled by BA at the transcriptional level, PAL1 and CHI are controlled by BA posttranscriptionally. CHS mRNA levels increased within 2 h of BA spray application, and peaked by 3 h. Levels of PAL1 mRNA did not increase within 6 h of BA spray. We also showed that PAL1, CHS, CHI, and DFR mRNA levels fluctuate during a 24-h period and appear to be controlled by a circadian clock. The relation between cytokinin regulation and light regulation of CHS gene transcription is discussed. PMID:12228453

Synthesis of 4-hydroxy-3-methylchalcone from Reimer-Tiemann reaction product and its antibacterial activity test

NASA Astrophysics Data System (ADS)

Hapsari, M.; Windarti, T.; Purbowatiningrum; Ngadiwiyana; Ismiyarto

2018-04-01

A 4-hydroxy-3-methylchalcone has been synthesized from 4-hydroxy-3-methylbenzaldehyde as the Reimer-Tiemann reaction product. This research consists of three steps involve synthesize of 4-hydroxy-3-methylbenzaldehyde from ortho-cresol, synthesize of chalcone derivatives from 4-hydroxy-3-methylbenzaldehyde and 4-hydroxy-3-methoxybenzaldehyde or vanillin for the comparison, the last is antibacterial activity test of both chalcone derivatives against Escherichia coli (negative gram) and Staphylococcus aureus (positive gram) bacteria using disc diffusion method. Results of Reimer-Tiemann reaction is 4-hydroxy-3-methylbenzaldehyde compound in an orange colour solid form which has 43% yields and melting point 110-114°C. A 4-hydroxy-3-methylbenzaldehyde then reacted with acetophenone in a base condition and form 4-hydroxy-3-methylchalcone compound in a yellow colour solid form which has 40% yields and melting point 83-86°C. The antibacterial activity of the 4-hydroxy-3-methylchalcone against gram-positive bacteria Staphylococcus aureus is better than the 4-hydroxy-3-methoxychalcone.

An In-Silico Investigation of Phytochemicals as Antiviral Agents Against Dengue Fever

PubMed Central

Powers, Chelsea N.; Setzer, William N.

2016-01-01

Abstract: A virtual screening analysis of our library of phytochemical structures with dengue virus protein targets has been carried out using a molecular docking approach. A total of 2194 plant-derived secondary metabolites have been docked. This molecule set comprised of 290 alkaloids (68 indole alkaloids, 153 isoquinoline alkaloids, 5 quinoline alkaloids, 13 piperidine alkaloids, 14 steroidal alkaloids, and 37 miscellaneous alkaloids), 678 terpenoids (47 monoterpenoids, 169 sesquiterpenoids, 265 diterpenoids, 81 steroids, and 96 triterpenoids), 20 aurones, 81 chalcones, 349 flavonoids, 120 isoflavonoids, 74 lignans, 58 stilbenoids, 169 miscellaneous polyphenolic compounds, 100 coumarins, 28 xanthones, 67 quinones, and 160 miscellaneous phytochemicals. Dengue virus protein targets examined included dengue virus protease (NS2B-NS3pro), helicase (NS3 helicase), methyltransferase (MTase), RNA-dependent RNA polymerase (RdRp), and the dengue virus envelope protein. Polyphenolic compounds, flavonoids, chalcones, and other phenolics were the most numerous of the strongly docking ligands for dengue virus protein targets. PMID:27151482

Stilbene synthase gene transfer caused alterations in the phenylpropanoid metabolism of transgenic strawberry (Fragaria×ananassa)

PubMed Central

Hanhineva, Kati; Kokko, Harri; Siljanen, Henri; Rogachev, Ilana; Aharoni, Asaph; Kärenlampi, Sirpa O.

2009-01-01

The gene encoding stilbene synthase is frequently used to modify plant secondary metabolism with the aim of producing the self-defence phytoalexin resveratrol. In this study, strawberry (Fragaria×ananassa) was transformed with the NS-Vitis3 gene encoding stilbene synthase from frost grape (Vitis riparia) under the control of the cauliflower mosaic virus 35S and the floral filament-specific fil1 promoters. Changes in leaf metabolites were investigated with UPLC-qTOF-MS (ultra performance liquid chromatography-quadrupole time of flight mass spectrometry) profiling, and increased accumulation of cinnamate, coumarate, and ferulate derivatives concomitantly with a decrease in the levels of flavonols was observed, while the anticipated resveratrol or its derivatives were not detected. The changed metabolite profile suggested that chalcone synthase was down-regulated by the genetic modification; this was verified by decreased chalcone synthase transcript levels. Changes in the levels of phenolic compounds led to increased susceptibility of the transgenic strawberry to grey mould fungus. PMID:19443619

Synthesis and antimicrobial evaluation of L-phenylalanine-derived C5-substituted rhodanine and chalcone derivatives containing thiobarbituric acid or 2-thioxo-4-thiazolidinone.

PubMed

Jin, Xin; Zheng, Chang-Ji; Song, Ming-Xia; Wu, Yan; Sun, Liang-Peng; Li, Yin-Jing; Yu, Li-Jun; Piao, Hu-Ri

2012-10-01

Four novel series of compounds, including the l-phenylalanine-derived C5-substituted rhodanine (6a-q, 7a-j) and chalcone derivatives containing thiobarbituric acid or 2-thioxo-4-thiazolidinone (9a-e, 11a-e) have been designed, synthesized, characterized, and evaluated for their antibacterial activity. Some of these compounds showed significant antibacterial activity against Gram-positive bacterias, especially against the strains of multidrug-resistant clinical isolates, among which compounds 6c-e, 6g, 6i, 6j and 6q exhibiting high levels of antimicrobial activity against Staphylococcus aureus RN4220 with minimum inhibitory concentration (MIC) values of 2 μg/mL. Compound 6q showed the most potent activity of all of the compounds against all of the test multidrug-resistant clinical isolates tested. Unfortunately, however, none of the compounds were active against Gram-negative bacteria at 64 μg/mL. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Substitution and solvent effects in the chalcones isomerization barrier of flavylium photochromic systems.

PubMed

Roque, Ana; Lima, João Carlos; Parola, A Jorge; Pina, Fernando

2007-04-01

Useful application of photochromic compounds as optical memories implies the existence of a large kinetic barrier between the forms interconverted by light. In the case of flavylium salts, the ground state isomerization barrier between the photoisomerizable chalcone isomers is shown to correlate with the electron donating ability of the substituents, measured by their effects in the (1)H NMR chemical shifts of the aromatic protons. Substitution with electron donating groups in ring A lowers the barrier while substitution at ring B has the opposite effect. However, in water, the observed increase is higher than expected in the case of compound 4',9-dihydroxychalcone when compared with the analogous 4'-dimethylamino-9-hydroxychalcone, containing a better electron donating group in the same position. Our interpretation is that the water network is providing an efficient pathway to form tautomers. In acetonitrile, unlike water, the expected order is indeed observed: E(a)(4',9-dihydroxychalcone) = 60 kJ mol(-1) < E(a) (4'-dimethylamino-9-hydroxychalcone) = 69 kJ mol(-1).

Antiproliferative activity and induction of apoptosis in PC-3 cells by the chalcone cardamonin from Campomanesia adamantium (Myrtaceae) in a bioactivity-guided study.

PubMed

Pascoal, Aislan Cristina Rheder Fagundes; Ehrenfried, Carlos Augusto; Lopez, Begoña Gimenez-Cassina; de Araujo, Thiago Matos; Pascoal, Vinicius D'ávila Bitencourt; Gilioli, Rovilson; Anhê, Gabriel Forato; Ruiz, Ana Lúcia Tasca Goes; Carvalho, João Ernesto de; Stefanello, Maria Elida Alves; Salvador, Marcos José

2014-02-07

The Myrtaceae family is a common source of medicines used in the treatment of numerous diseases in South America. In Brazil, fruits of the Campomanesia species are widely used to make liqueurs, juices and sweets, whereas leaves are traditionally employed as a medicine for dysentery, stomach problems, diarrhea, cystitis and urethritis. Ethanol extracts of Campomanesia adamantium (Myrtaceae) leaves and fruits were evaluated against prostate cancer cells (PC-3). The compound (2E)-1-(2,4-dihydroxy-6-methoxyphenyl)-3-phenylprop-2-en-1-one, cardamonin) was isolated from ethanol extracts of C. adamantium leaves in a bioactivity-guided study and quantified by UPLC-MS/MS. In vitro studies showed that the isolated chalcone cardamonin inhibited prostate cancer cell proliferation and decreased the expression of NFkB1. Moreover, analysis by flow cytometry showed that this compound induced DNA fragmentation, suggesting an effect on apoptosis induction in the PC-3 cell line.

Antifungal dimeric chalcone derivative kamalachalcone E from Mallotus philippinensis.

PubMed

Kulkarni, Roshan R; Tupe, Santosh G; Gample, Suwarna P; Chandgude, Macchindra G; Sarkar, Dhiman; Deshpande, Mukund V; Joshi, Swati P

2014-01-01

From the red coloured extract (Kamala) prepared through acetone extraction of the fresh whole uncrushed fruits of Mallotus philippinensis, one new dimeric chalcone (1) along with three known compounds 1-(5,7-dihydroxy-2,2,6-trimethyl-2H-1-benzopyran-8-yl)-3-phenyl-2-propen-1-one (2), rottlerin (3) and 4'-hydroxyrottlerin (4) were isolated. The structure of compound 1 was elucidated by 1D and 2D NMR analyses that included HSQC, HMBC, COSY and ROESY experiments along with the literature comparison. Compounds 1-4 were evaluated for antifungal activity against different human pathogenic yeasts and filamentous fungi. The antiproliferative activity of the compounds was evaluated against Thp-1 cell lines. Compounds 1 and 2 both exhibited IC50 of 8, 4 and 16 μg/mL against Cryptococcus neoformans PRL518, C. neoformans ATCC32045 and Aspergillus fumigatus, respectively. Compound 4, at 100 μg/mL, showed 54% growth inhibition of Thp-1 cell lines.

Synthesis of novel fluorinated chalcones derived from 4‧-morpholinoacetophenone and their antiproliferative effects

NASA Astrophysics Data System (ADS)

Kurşun Aktar, Bedriye Seda; Oruç-Emre, Emine Elçin; Demirtaş, Ibrahim; Yaglioglu, Ayse Sahin; Guler, Caglar; Adem, Sevki; Karaküçük Iyidoğan, Ayşegül

2017-12-01

The fluorinated chalcones were synthesized by Claisen-Schmidt condensation between 4‧-morpholineacetophenone and various fluorinated benzaldehydes in the presence of NaOH in methanol. The synthesized compounds [1-7] were evaluated their antiproliferative activity against HeLa and C6 cell lines. Among them, compounds 4 and 5 were determined to have anticancer activity against HeLa cells line (IC50 values of 7.74 and 6.10 μg/mL, respectively). The anticancer activity results were shown that compounds 3, and 6 had inhibitory against C6 cells (IC50 values of 12.80 and 4.16 μg/mL, respectively). The compounds 1 and 2 had high antiproliferative activity with non-cytotoxicity. All of the new compounds, except for compound 4 showed inhibition against the human isozyme hCA I with IC50 in the range of 0.5-1,16 mM. Pyruvate kinase M2 (PKM2) was effectively inhibited by compound 4 with IC50 = 26 μM.

Discovery of potent cytotoxic ortho-aryl chalcones as new scaffold targeting tubulin and mitosis with affinity-based fluorescence.

PubMed

Zhu, Cuige; Zuo, Yinglin; Wang, Ruimin; Liang, Baoxia; Yue, Xin; Wen, Gesi; Shang, Nana; Huang, Lei; Chen, Yu; Du, Jun; Bu, Xianzhang

2014-08-14

A series of new ortho-aryl chalcones have been designed and synthesized. Many of these compounds were found to exhibit significant antiproliferation activity toward a panel of cancer cell lines. Selected compounds show potent cytotoxicity against several drug resistant cell lines including paclitaxel (Taxol) resistant human ovarian carcinoma cells, vincristine resistant human ileocecum carcinoma cells, and doxorubicin resistant human breast carcinoma cells. Further investigation revealed that active analogues could inhibit the microtubule polymerization by binding to colchicine site and thus induce multipolar mitosis, G2/M phase arrest, and apoptosis of cancer cells. Furthermore, affinity-based fluorescence enhancement was observed during the binding of active compounds with tubulin, which greatly facilitated the determination of tubulin binding site of the compounds. Finally, selected compound 26 was found to exhibit obvious in vivo antitumor activity in A549 tumor xenografts model. Our systematic studies implied a new scaffold targeting tubulin and mitosis for novel antitumor drug discovery.

Flavylium network of chemical reactions in confined media: modulation of 3',4',7-trihydroxyflavilium reactions by host-guest interactions with cucurbit[7]uril.

PubMed

Basílio, Nuno; Pina, Fernando

2014-08-04

In moderately acidic aqueous solutions, flavylium compounds undergo a pH-, and in some cases, light-dependent array of reversible chemical reactions. This network can be described as a single acid-base reaction involving a flavylium cation (acidic form) and a mixture of basic forms (quinoidal base, hemiketal and cis and trans chalcones). The apparent pK'a of the system and the relative mole fractions of the basic forms can be modulated by the interaction with cucurbit[7]uril. The system is studied by using (1) H NMR spectroscopy, UV/Vis spectroscopy, flash photolysis, and steady-state irradiation. Of all the network species, the flavylium cation possesses the highest affinity for cucurbit[7]uril. The rate of interconversion between flavylium cation and the basic species (where trans-chalcone is dominant) is approximately nine times lower inside the cucurbit[7]uril. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A comparative study of conventional and supercritical fluid extraction methods for the recovery of secondary metabolites from Syzygium campanulatum Korth.

PubMed

Memon, Abdul Hakeem; Hamil, Mohammad Shahrul Ridzuan; Laghari, Madeeha; Rithwan, Fahim; Zhari, Salman; Saeed, Mohammed Ali Ahmed; Ismail, Zhari; Majid, Amin Malik Shah Abdul

2016-09-01

Syzygium campanulatum Korth is a plant, which is a rich source of secondary metabolites (especially flavanones, chalcone, and triterpenoids). In our present study, three conventional solvent extraction (CSE) techniques and supercritical fluid extraction (SFE) techniques were performed to achieve a maximum recovery of two flavanones, chalcone, and two triterpenoids from S. campanulatum leaves. Furthermore, a Box-Behnken design was constructed for the SFE technique using pressure, temperature, and particle size as independent variables, and yields of crude extract, individual and total secondary metabolites as the dependent variables. In the CSE procedure, twenty extracts were produced using ten different solvents and three techniques (maceration, soxhletion, and reflux). An enriched extract of five secondary metabolites was collected using n-hexane:methanol (1:1) soxhletion. Using food-grade ethanol as a modifier, the SFE methods produced a higher recovery (25.5%‒84.9%) of selected secondary metabolites as compared to the CSE techniques (0.92%‒66.00%).

A comparative study of conventional and supercritical fluid extraction methods for the recovery of secondary metabolites from Syzygium campanulatum Korth#

PubMed Central

Memon, Abdul Hakeem; Hamil, Mohammad Shahrul Ridzuan; Laghari, Madeeha; Rithwan, Fahim; Zhari, Salman; Saeed, Mohammed Ali Ahmed; Ismail, Zhari; Majid, Amin Malik Shah Abdul

2016-01-01

Syzygium campanulatum Korth is a plant, which is a rich source of secondary metabolites (especially flavanones, chalcone, and triterpenoids). In our present study, three conventional solvent extraction (CSE) techniques and supercritical fluid extraction (SFE) techniques were performed to achieve a maximum recovery of two flavanones, chalcone, and two triterpenoids from S. campanulatum leaves. Furthermore, a Box-Behnken design was constructed for the SFE technique using pressure, temperature, and particle size as independent variables, and yields of crude extract, individual and total secondary metabolites as the dependent variables. In the CSE procedure, twenty extracts were produced using ten different solvents and three techniques (maceration, soxhletion, and reflux). An enriched extract of five secondary metabolites was collected using n-hexane:methanol (1:1) soxhletion. Using food-grade ethanol as a modifier, the SFE methods produced a higher recovery (25.5%‒84.9%) of selected secondary metabolites as compared to the CSE techniques (0.92%‒66.00%). PMID:27604860

Effect of selected dimethylaminochalcones on some mitochondrial activities.

PubMed

Vašková, Janka; Reisch, Renáta; Vaško, Ladislav; Poškrobová, Martina; Kron, Ivan; Guzy, Juraj; Perjési, Pál

2013-05-01

Chalcones and their synthetic cyclic analogues have been shown to possess a full scale of biological activities in a variety of experimental systems. They were assessed to be mostly effective in defense against free radicals in the organism, but several compounds exhibited cytotoxic pro-oxidant activities. The respiratory response and antioxidant status in mitochondria were investigated upon addition of 4'-dimethylaminochalcone (1a) and its cyclic analogues, (E)-2-(4'-((CH3)2 N)-benzylidene)-1-indanone (1b), -1-tetralone (1c), and -1-benzosuberone (1d). Selected structures were able to change the respiratory response of mitochondria and showed an ability to modify mitochondrial metabolic and redox efficiency, though they did not indicate redox reactivity towards glutathione in adduct-free incubations. The results of the study indicate that -chalcone and -tetralone derivatives cause suppression of reactive oxygen species affecting mitochondrial respiration by mild uncoupling. In addition, (E)-2-(4'-((CH3)2 N)-indanone (1b), and to a greater extent, -benzosuberone (1d), showed pro-oxidant effects, which partially explain their cytotoxicity.

A study of anti-inflammatory and analgesic activity of new 2,4,6-trisubstituted pyrimidines.

PubMed

Yejella, Rajendra Prasad; Atla, Srinivasa Rao

2011-01-01

Chalcone derivatives (3a-m) were prepared by condensing 4-aminoacetophenone with various substituted aromatic and hetero aromatic aldehydes according to Claisen-Schmidt condensation. These chalcones, on reaction with guanidine hydrochloride under basic alcoholic conditions gave 2,4,6-trisubstituted pyrimidines (5a-m) in quantitative yields. All the newly synthesized pyrimidines were characterized by means of IR, ¹H- and ¹³C-NMR, Electron Ionization (EI)-mass and elemental analyses and screened for anti-inflammatory and analgesic activities by in vivo. 2-amino-4-(4-aminophenyl)-6-(2,4-dichlorophenyl)pyrimidine (5b) and 2-amino-4-(4-aminophenyl)-6-(3-bromophenyl) pyrimidine (5d) were found to be the most potent anti-inflammatory and analgesic activity compared with ibuprofen, reference standard. And also it was found that compound 5b identified as lead structure among all in both the activities. Pyrimidines which showed good anti-inflammatory activity also displayed better analgesic activity.

The Cytoprotective Effects of E-α-(4-Methoxyphenyl)-2’,3,4,4'-Tetramethoxychalcone (E-α-p-OMe-C6H4-TMC)—A Novel and Non-Cytotoxic HO-1 Inducer

PubMed Central

Kaufmann, Kai B.; Al-Rifai, Nafisah; Ulbrich, Felix; Schallner, Nils; Rücker, Hannelore; Enzinger, Monika; Petkes, Hermina; Pitzl, Sebastian

2015-01-01

Cell protection against different noxious stimuli like oxidative stress or chemical toxins plays a central role in the treatment of many diseases. The inducible heme oxygenase isoform, heme oxygenase-1 (HO-1), is known to protect cells against a variety of harmful conditions including apoptosis. Because a number of medium strong electrophiles from a series of α-X-substituted 2’,3,4,4’-tetramethoxychalcones (α-X-TMCs, X = H, F, Cl, Br, I, CN, Me, p-NO2-C6H4, Ph, p-OMe-C6H4, NO2, CF3, COOEt, COOH) had proven to activate Nrf2 resulting in HO-1 induction and inhibit NF-κB downstream target genes, their protective effect against staurosporine induced apoptosis and reactive oxygen species (ROS) production was investigated. RAW264.7 macrophages treated with 19 different chalcones (15 α-X-TMCs, chalcone, 2’-hydroxychalcone, calythropsin and 2’-hydroxy-3,4,4’-trimethoxychalcone) prior to staurosporine treatment were analyzed for apoptosis and ROS production, as well as HO-1 protein expression and enzyme activity. Additionally, Nrf2 and NF-κB activity was assessed. We found that amongst all tested chalcones only E-α-(4-methoxyphenyl)-2’,3,4,4'-tetramethoxychalcone (E-α-p-OMe-C6H4-TMC) demonstrated a distinct, statistically significant antiapoptotic effect in a dose dependent manner, showing no toxic effects, while its double bond isomer Z-α-p-OMe-C6H4-TMC displayed no significant activity. Also, E-α-p-OMe-C6H4-TMC induced HO-1 protein expression and increased HO-1 activity, whilst inhibition of HO-1 by SnPP-IX abolished its antiapoptotic effect. The only weakly electrophilic chalcone E-α-p-OMe-C6H4-TMC reduced the staurosporine triggered formation of ROS, while inducing the translocation of Nrf2 into the nucleus. Furthermore, staurosporine induced NF-κB activity was attenuated following E-α-p-OMe-C6H4-TMC treatment. Overall, E-α-p-OMe-C6H4-TMC demonstrated its effective cytoprotective potential via a non-toxic induction of HO-1 in RAW264.7 macrophages. The observed cytoprotective effect may partly be related to both, the activation of the Nrf2- and inhibition of the NF-κB pathway. PMID:26565402

Toxicity and synergistic activities of Chalcones against Aedes aegypti (Diptera: Culicidae) and Drosophila melanogaster (Diptera: Drosophilidae)

USDA-ARS?s Scientific Manuscript database

Mosquito-borne illnesses are of great concern throughout the world, and chemical insecticides are commonly employed to decrease mosquito populations. However, the developmental insecticide pipeline for vector control has primarily been filled by repurposed agricultural products, and is hampered by t...

Glyceollin is an important component of soybean plant defense against Phytophthora sojae and Macrophomina phaseolina

USDA-ARS?s Scientific Manuscript database

Transgenic soybean plants were generated using bombardment of embryogenic cultures with the PAL5 (phenylalanine ammonia lyase), CHS6 (chalcone synthase) and IFS2 (isoflavone synthase) genes in sense orientation, driven by the cotyledon-preferable lectin promoter, or with the IFS2 (isoflavone synthas...

Eco-friendly Synthesis of Ceria Foam via Carboxymethylcellulose Gelation: Application for the Epoxidation of Chalcone

EPA Science Inventory

A simple and innovative process is described for the eco-friendly preparation of ceria foams via the carboxymethylcellulose gelation by Ce4+ cations; heat treatment of the ensuing xerogels produces ceria foams. The influence of the concentration of cerium and of the calcination t...

Non-linear optical properties of arylfuranylpropenones

NASA Astrophysics Data System (ADS)

Holla, B. Shivarama; Veerendra, B.; Indira, J.

2003-05-01

A series of arylfuranylpropenones 3a-i were synthesized by the reaction of 5-(2-nitro-4-methoxyphenyl)-2-furfural 1 with various acetophenones 2 by Claisen-Schmidt condensation. All the newly synthesized chalcones were characterized by elemental analysis and spectral studies. Most of them showed SHG conversion efficiency in powder form.

Mosquito activity of a series of chalcones and 2-pyrazoline derivatives against Aedes aegypti

USDA-ARS?s Scientific Manuscript database

Aedes aegypti (L.) (Diptera: Culicidae) transmit pathogens to humans, leading to diseases such as yellow fever and dengue fever. Repellents and insecticides are two common interventions to reduce mosquito biting and thereby disease risk. However, overreliance on a chemical or class of chemicals c...

Synthesis, growth, structural characterization, Hirshfeld analysis and nonlinear optical studies of a methyl substituted chalcone

NASA Astrophysics Data System (ADS)

Prabhu, Shobha R.; Jayarama, A.; Chandrasekharan, K.; Upadhyaya, V.; Ng, Seik Weng

2017-05-01

A new chalcone compound (2E)-3-(3-methylphenyl)-1-(4-nitrophenyl)prop-2-en-1-one (3MPNP) with molecular formula C16H13NO3 has been synthesized and crystallized by slow solvent evaporation technique. The Fourier transform infrared, Fourier transform Raman and nuclear magnetic resonance techniques were used for structural characterization. UV-visible absorption studies were carried out to study the transparency of the crystal in the visible region. Differential scanning calorimetry study shows thermal stability of crystals up to temperature 122 °C. Single crystal X-ray diffraction and powder X-ray diffraction techniques were used to study crystal structure and cell parameters. The Hirshfeld surface and 2-D fingerprint analysis were performed to study the nature of interactions and their quantitative contributions towards the crystal packing. The third order non-linear optical properties have been studied using single beam Z-scan technique and the results show that the material is a potential candidate for optical device applications such as optical limiters and optical switches.

A Proteolytic Regulator Controlling Chalcone Synthase Stability and Flavonoid Biosynthesis in Arabidopsis

DOE PAGES

Zhang, Xuebin; Abrahan, Carolina; Colquhoun, Thomas A.; ...

2017-04-26

Flavonoids represent a large family of specialized metabolites involved in plant growth, development, and adaptation. Chalcone synthase (CHS) catalyzes the first step of flavonoid biosynthesis by directing carbon flux from general phenylpropanoid metabolism to flavonoid pathway. Despite extensive characterization of its function and transcriptional regulation, the molecular basis governing its posttranslational modification is enigmatic. Here, we report the discovery of a proteolytic regulator of CHS, namely, KFB CHS, a Kelch domain-containing F-box protein in Arabidopsis thaliana. KFB CHS physically interacts with CHS and specifically mediates its ubiquitination and degradation. KFB CHS exhibits developmental expression patterns in Arabidopsis leaves, stems, andmore » siliques and strongly responds to the dark-to-light (or the light-to-dark) switch, the blue, red, and far-red light signals, and UV-B irradiation. Alteration of KFB CHS expression negatively correlates to the cellular concentration of CHS and the production of flavonoids. Our study suggests that KFB CHS serves as a crucial negative regulator, via mediating CHS degradation, coordinately controlling flavonoid biosynthesis in response to the developmental cues and environmental stimuli.« less

Design, synthesis and antileishmanial in vitro activity of new series of chalcones-like compounds: a molecular hybridization approach.

PubMed

Barbosa, Ticiano P; Sousa, Suervy C O; Amorim, Francianne M; Rodrigues, Yara K S; de Assis, Priscilla A C; Caldas, John P A; Oliveira, Márcia R; Vasconcellos, Mário L A A

2011-07-15

The chalcone-like series 1a-1g was efficiently synthesized from Morita-Baylis-Hillman reaction (52-74% yields). Compounds 1a-1g were designed by molecular hybridization based on the anti-inflammatory drug methyl salicylate (3) and the antileishmanial moiety of the Morita-Baylis-Hillman adducts 2a-2g. The 1a-1g compounds were much more actives than precursor series 2a-2g, for example, IC(50)=7.65 μM on Leishmania amazonensis and 10.14 μM on Leishmania chagasi (compound 1c) when compared to IC(50)=50.08 μM on L. amazonensis and 82.29 μM on L. chagasi (compound 2c). The IC(50) values of compound 3 (228.49 μM on L. amazonensis and 261.45 μM on L. chagasi) and acryloyl salicylate 4 (108.50 μM on L. amazonensis and 118.83 μM on L. chagasi) were determined here, by the first time, on Leishmania. Copyright © 2011 Elsevier Ltd. All rights reserved.

Bioactive Compounds from Vitex leptobotrys#

PubMed Central

Pan, Wenhui; Liu, Kanglun; Guan, Yifu; Tan, Ghee Teng; Hung, Nguyen Van; Cuong, Nguyen Manh; Soejarto, D. Doel; Pezzuto, John M.; Fong, Harry H.S.; Zhang, Hongjie

2014-01-01

A new lignan, vitexkarinol (1), as well as a known lignan, neopaulownin (2), a known chalcone, 3-(4-hydroxyphenyl)-1-(2,4,6-trimethoxyphenyl)-2-propen-1-one (3), two known dehydroflavones, tsugafolin (4) and alpinetin (5), two known dipeptides, aurantiamide and aurantiamide acetate, a known sesquiterpene, vemopolyanthofuran, and five known carotenoid metabolites, vomifoliol, dihydrovomifoliol, dehydrovomifoliol, loliolide and isololiolide, were isolated from the leaves and twigs of Vitex leptobotrys through bioassay-guided fractionation. The chalcone (3) was found to inhibit HIV-1 replication by 77% at 15.9 µM, and the two dehydroflavones (4 and 5) showed weak anti-HIV activity with IC50 values of 118 and 130 µM, respectively, while being devoid of cytotoxicity at 150 µM. A chlorophyll-enriched fraction of V. leptobotrys, containing pheophorbide a, was found to inhibit the replication of HIV-1 by 80% at a concentration of 10 µg/mL. Compounds 1 and 3 were further selected to be evaluated against 21 viral targets available at NIAID (National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD). PMID:24404757

Organocatalytic aza-Michael/retro-aza-Michael reaction: pronounced chirality amplification in aza-Michael reaction and racemization via retro-aza-Michael reaction.

PubMed

Cai, Yong-Feng; Li, Li; Luo, Meng-Xian; Yang, Ke-Fang; Lai, Guo-Qiao; Jiang, Jian-Xiong; Xu, Li-Wen

2011-05-01

A detailed experimental investigation of an aza-Michael reaction of aniline and chalcone is presented. A series of Cinchona alkaloid-derived organocatalysts with different functional groups were prepared and used in the aza-Michael and retro-aza-Michael reaction. There was an interesting finding that a complete reversal of stereoselectivity when a benzoyl group was introduced to the cinchonine and cinchonidine. The chirality amplification vs. time proceeds in the quinine-derived organocatalyst containing silicon-based bulky group, QN-TBS, -catalyzed aza-Michael reaction under solvent-free conditions. In addition, we have demonstrated for the first time that racemization was occurred in suitable solvents under mild conditions due to retro-aza-Michael reaction of the Michael adduct of aniline with chalcone. These indicate the equilibrium of retro-aza-Michael reaction and aza-Michael reaction produce the happening of chirality amplification in aza-Michael reaction and racemization via retro-aza-Michael reaction under different conditions, which would be beneficial to the development of novel chiral catalysts for the aza-Michael reactions. Copyright © 2011 Wiley-Liss, Inc.

Virus-Induced Gene Silencing of the Eggplant Chalcone Synthase Gene during Fruit Ripening Modifies Epidermal Cells and Gravitropism.

PubMed

Wang, Cuicui; Fu, Daqi

2018-03-21

Eggplant ( Solanum melongena L.) fruits accumulate flavonoids in their cuticle and epidermal cells during ripening. Although many mutants available in model plant species, such as Arabidopsis thaliana and Medicago truncatula, are enabling the intricacies of flavonoid-related physiology to be deduced, the mechanisms whereby flavonoids influence eggplant fruit physiology are unknown. Virus-induced gene silencing (VIGS) is a reliable tool for the study of flavonoid function in fruit, and in this study, we successfully applied this technique to downregulate S. melongena chalcone synthase gene ( SmCHS) expression during eggplant fruit ripening. In addition to the expected change in fruit color attributable to a lack of anthocyanins, several other modifications, including differences in epidermal cell size and shape, were observed in the different sectors. We also found that silencing of CHS gene expression was associated with a negative gravitropic response in eggplant fruits. These observations indicate that epidermal cell expansion during ripening is dependent upon CHS expression and that there may be a relationship between CHS expression and gravitropism during eggplant fruit ripening.

Antioxidant chalcone glycosides and flavanones from Maclura (Chlorophora) tinctoria.

PubMed

Cioffi, Giuseppina; Morales Escobar, Luis; Braca, Alessandra; De Tommasi, Nunziatina

2003-08-01

Four chalcone glycosides (1-4), including three new natural products, and three flavanones (5-7) were isolated from the methanol extract of stem bark of Maclura tinctoria. The new compounds have been characterized as 4'-O-beta-D-(2' '-p-coumaroyl)glucopyranosyl-4,2',3'-trihydroxychalcone (1), 4'-O-beta-D-(2' '-p-coumaroyl-6' '-acetyl)glucopyranosyl-4,2',3'-trihydroxychalcone (2), and 3'-(3-methyl-2-butenyl)-4'-O-beta-D-glucopyranosyl-4,2'-dihydroxychalcone (3); the known derivatives were elucidated as 4'-O-beta-D-(2' '-acetyl-6' '-cinnamoyl)glucopyranosyl-4,2',3'-trihydroxychalcone (4), eriodictyol 7-O-beta-D-glucopyranoside (5), naringenin (6), and naringenin 4'-O-beta-D-glucopyranoside (7). Their structures were determined by 1D and 2D NMR and ESIMS. The antioxidant activity of all the isolated compounds was determined by measuring free-radical-scavenging effects using two different assays, namely, the Trolox Equivalent Antioxidant Capacity (TEAC) assay and the coupled oxidation of beta-carotene and linoleic acid (autoxidation assay). The results showed that compound 3 was the most active in both antioxidant assays.

Isolation, identification and usefulness of antifungal compounds from Zuccagnia punctata for control of toxigenic ear rot pathogens.

PubMed

Jimenez, Cristina M; Sampietro, Diego A; Sgariglia, Melina A; Soberón, José R; Vattuone, Marta A

2014-10-01

Infusion, tincture and decoction of leaves of Zuccagnia punctata Cav. were assayed on growth of Fusarium verticillioides, F. graminearum sensu stricto, F. boothii, F. meridionale, F. subglutinans and F. thapsinum. The tincture showed the lowest IC50 on mycelial growth. A diethyl ether fraction of the tincture showed the highest antifungal activity in microdilution assays on F. verticillioides and F. graminearum. The antifungal constituents were separated by silica gel chromatography and identified as 2',4'-dihydroxychalcone, 2',4'-dihydroxy-3'-methoxychalcone and 7-hydroxy-3',4'-dimethoxyflavone. These chalcones had the lowest MIC and MFC values on F. verticillioides and F. graminearum sensu stricto. 2',4'-Dihydroxychalcone was mildly toxic and the remaining identified compounds were non-toxic in the brine shrimp assay. 2',4'-Dihydroxychalcone in mixtures with commercial food preservatives showed additive effects on F. graminearum sensu stricto and synergistic ones on F. verticillioides. 2',4'-Dihydroxy-3'-methoxychalcone showed synergistic effects in mixtures. Our results suggest that addition of chalcones to food preservatives allows reduction in the doses of the preservatives required for control of Fusarium species.

Use of cyclodextrins in biotransformation reactions with cell cultures of Morus nigra: biosynthesis of prenylated chalcone isocordoin.

PubMed

Bolasco, Adriana; Fioravanti, Rossella; Rossi, Francesca; Rossi, Paola; Vitali, Alberto

2010-06-16

In vivo biotransformation experiments were performed by using a cell suspension culture of Morus nigra expressing a high PT (prenyltransferase) activity, fed with the target substrate 2',4'-dihydroxychalcone. In order to improve the reaction yields by enhancing the chalcone solubility, three different cyclodextrins have been used to host the substrate. The respective complexes have been studied by means of both spectroscopic and calorimetric techniques (Fourier-transform infrared, 1H-NMR and differential scanning calorimetry) and the solution behaviours have been characterized by solubility phase studies. The hydroxypropyl-beta-cyclodextrin complex was found to be the most suitable for biotransformation, and the reaction of prenylation resulted in a 6-fold higher yield of the final product when compared with the use of the free substrate. The reaction provided as the sole product the 3'-dimethylallyl derivative isocordoin, a biologically active plant compound. The results obtained allow the development of systems based on the use of biofermentors or the use of immobilized cells in order to enhance the biotransformation yields.

Study on structural and spectral properties of isobavachalcone and 4-hydroxyderricin by computational method

NASA Astrophysics Data System (ADS)

Rong, Yuzhi; Wu, Jinhong; Liu, Xing; Zhao, Bo; Wang, Zhengwu

Isobavachalcone and 4-hydroxyderricin, two major chalcone constituents isolated from the roots of Angelica keiskei KOIDZUMI, exhibit numerous biological activities. Quantum chemical methods have been employed to investigate their structural and spectral properties. The ground state structures were optimized using density functional B3LYP method with 6-311G (d, p) basis set in both gas and solvent phases. Based on the optimized geometries, the harmonic vibrational frequency, the 1H and 13C nuclear magnetic resonance (NMR) chemical shift using the GIAO method were calculated at the same level of theory, with the aim of verifying the experimental values. Results reveal that B3LYP has been a good method to study their vibrational spectroscopic and NMR spectral properties of the two chalcones. The electronic absorption spectra were calculated using the time-dependent density functional theory (TDDFT) method. The solvent polarity effects were considered and calculated using the polarizable continuum model (PCM). Results also show that substitutions of different electron donating groups can alter the absorption properties and shift the spectra to a higher wavelength region.

Synthesis, antimicrobial, anti-biofilm evaluation, and molecular modelling study of new chalcone linked amines derivatives.

PubMed

El-Messery, Shahenda M; Habib, El-Sayed E; Al-Rashood, Sarah T A; Hassan, Ghada S

2018-12-01

A series of amide chalcones conjugated with different secondary amines were synthesised and characterised by different spectroscopic techniques 1 H NMR, 13 C NMR, and ESI-MS. They were screened for in vitro antibacterial activity. Compounds 36, 37, 38, 42, and 44 are the most active among the synthesised series exhibiting MIC value of 2.0-10.0 µg/ml against different bacterial strains. Compound 36 was equipotent to the standard drug Ampicillin displaying MBC value of 2.0 µg/ml against the bacterial strain Staphylococcus aureus. The products were screened for anti-biofilm activity. Compounds 36, 37, and 38 exhibited promising anti-biofilm activity with IC 50 value ranges from 2.4 to 8.6 µg. Molecular modelling was performed suggesting parameters of signalling anti-biofilm mechanism. AspB327 HisB340 (arene-arene interaction) and IleB328 amino acid residues seemed of higher importance to inhibit c-di-GMP. Hydrophobicity may be crucial for activity. ADME calculations suggested that compounds 36, 37, and 38 could be used as good orally absorbed anti-biofilm agents.

Synthesis, Structure–Activity Relationship Studies, and Antibacterial Evaluation of 4-Chromanones and Chalcones, as Well as Olympicin A and Derivatives

PubMed Central

2015-01-01

On the basis of recently reported abyssinone II and olympicin A, a series of chemically modified flavonoid phytochemicals were synthesized and evaluated against Mycobacterium tuberculosis and a panel of Gram-positive and -negative bacterial pathogens. Some of the synthesized compounds exhibited good antibacterial activities against Gram-positive pathogens including methicillin resistant Staphylococcus aureus with minimum inhibitory concentration as low as 0.39 μg/mL. SAR analysis revealed that the 2-hydrophobic substituent and the 4-hydrogen bond donor/acceptor of the 4-chromanone scaffold together with the hydroxy groups at 5- and 7-positions enhanced antibacterial activities; the 2′,4′-dihydroxylated A ring and the lipophilic substituted B ring of chalcone derivatives were pharmacophoric elements for antibacterial activities. Mode of action studies performed on selected compounds revealed that they dissipated the bacterial membrane potential, resulting in the inhibition of macromolecular biosynthesis; further studies showed that selected compounds inhibited DNA topoisomerase IV, suggesting complex mechanisms of actions for compounds in this series. PMID:25238443

Emerging role of Garcinol, the antioxidant chalcone from Garcinia indica Choisy and its synthetic analogs

PubMed Central

Padhye, Subhash; Ahmad, Aamir; Oswal, Nikhil; Sarkar, Fazlul H

2009-01-01

Garcinol, harvested from Garcinia indica, has traditionally been used in tropical regions and appreciated for centuries; however its biological properties are only beginning to be elucidated. There is ample data to suggest potent antioxidant properties of this compound which have been used to explain most of its observed biological activities. However, emerging evidence suggests that garcinol could be useful as an anti-cancer agent, and it is increasingly being realized that garcinol is a pleiotropic agent capable of modulating key regulatory cell signaling pathways. Here we have summarized the progress of our current research knowledge on garcinol and its observed biological activities. We have also provided an explanation of observed properties based on its chemical structure and provided an insight into the structure and properties of chalcones, the precursors of garcinol. The available data is promising but more detailed investigations into the various properties of this compound, particularly its anti-cancer activity are urgently needed, and it is our hope that this review will stimulate further research for elucidating and appreciating the value of this nature's wonder agent. PMID:19725977

Emerging role of Garcinol, the antioxidant chalcone from Garcinia indica Choisy and its synthetic analogs.

PubMed

Padhye, Subhash; Ahmad, Aamir; Oswal, Nikhil; Sarkar, Fazlul H

2009-09-02

Garcinol, harvested from Garcinia indica, has traditionally been used in tropical regions and appreciated for centuries; however its biological properties are only beginning to be elucidated. There is ample data to suggest potent antioxidant properties of this compound which have been used to explain most of its observed biological activities. However, emerging evidence suggests that garcinol could be useful as an anti-cancer agent, and it is increasingly being realized that garcinol is a pleiotropic agent capable of modulating key regulatory cell signaling pathways. Here we have summarized the progress of our current research knowledge on garcinol and its observed biological activities. We have also provided an explanation of observed properties based on its chemical structure and provided an insight into the structure and properties of chalcones, the precursors of garcinol. The available data is promising but more detailed investigations into the various properties of this compound, particularly its anti-cancer activity are urgently needed, and it is our hope that this review will stimulate further research for elucidating and appreciating the value of this nature's wonder agent.

Synthesis, fluorescence, TGA and crystal structure of thiazolyl-pyrazolines derived from chalcones

NASA Astrophysics Data System (ADS)

Suwunwong, T.; Chantrapromma, S.; Fun, H.-K.

2015-04-01

Thiazolyl-pyrazolines 3a-3d were synthesized in a three step procedure using chalcones as starting materials and characterized by FT-IR, UV-Vis, and 1H NMR techniques. The crystal structure of compound 3a was also determined by X-ray diffraction analysis. Compound 3a crystallized out in the orthorhombic P212121 space group with the unit cell dimensions: a = 5.2106(2) Å, b = 12.4341(5) Å, c = 33.3254(13) Å, α = β = γ = 90°, V = 2159.12(15) Å3, Z = 4, D cald = 1.372 M gm-3 and F(000) = 928. Fluorescence of 3a-3d were studied in solid state and acetonitrile solution. It was found that, these compounds exhibit the green fluorescence light (506-508 nm) in both solid and solution states. The pH stability on fluorescence property and the thermal gravimetric analysis of compound 3a were specifically carried out. It was revealed that 3a shows high thermal stability up to around 250°C and presenting high stability in various pH ranges in the acetonitrilewater matrix.

A Proteolytic Regulator Controlling Chalcone Synthase Stability and Flavonoid Biosynthesis in Arabidopsis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Xuebin; Abrahan, Carolina; Colquhoun, Thomas A.

Flavonoids represent a large family of specialized metabolites involved in plant growth, development, and adaptation. Chalcone synthase (CHS) catalyzes the first step of flavonoid biosynthesis by directing carbon flux from general phenylpropanoid metabolism to flavonoid pathway. Despite extensive characterization of its function and transcriptional regulation, the molecular basis governing its posttranslational modification is enigmatic. Here, we report the discovery of a proteolytic regulator of CHS, namely, KFB CHS, a Kelch domain-containing F-box protein in Arabidopsis thaliana. KFB CHS physically interacts with CHS and specifically mediates its ubiquitination and degradation. KFB CHS exhibits developmental expression patterns in Arabidopsis leaves, stems, andmore » siliques and strongly responds to the dark-to-light (or the light-to-dark) switch, the blue, red, and far-red light signals, and UV-B irradiation. Alteration of KFB CHS expression negatively correlates to the cellular concentration of CHS and the production of flavonoids. Our study suggests that KFB CHS serves as a crucial negative regulator, via mediating CHS degradation, coordinately controlling flavonoid biosynthesis in response to the developmental cues and environmental stimuli.« less

Novel trans-Ferulic Acid Derivatives Containing a Chalcone Moiety as Potential Activator for Plant Resistance Induction.

PubMed

Gan, Xiuhai; Hu, Deyu; Wang, Yanjiao; Yu, Lu; Song, Baoan

2017-06-07

A series of novel trans-ferulic acid derivatives containing a chalcone moiety were designed and synthesized to induce plant resistance. Antiviral activities of the compounds were evaluated. Bioassay results demonstrated that compounds F3, F6, F17, and F27 showed remarkable curative, protective, and inactivating activities against tobacco mosaic virus (TMV). With a 50% effective concentration (EC 50 ) value of 98.78 μg mL -1 , compound F27 exhibited the best protective activity compared with trans-ferulic acid (328.6 μg mL -1 ), dufulin (385.6 μg mL -1 ), and ningnanmycin (241.3 μg mL -1 ). This protective ability was associated with potentiation of defense-related enzyme activity and activation of photosynthesis of tobacco at an early stage. This notion was confirmed by up-regulated expression of stress responses and photosynthesis regulating proteins. This work revealed that F27 can induce resistance and enhance plant tolerance to TMV infection. Hence, F27 can be considered as a novel activator for inducing plant resistance.

Design and synthesis of chalcone derivatives as potent tyrosinase inhibitors and their structural activity relationship

NASA Astrophysics Data System (ADS)

Akhtar, Muhammad Nadeem; Sakeh, Nurshafika M.; Zareen, Seema; Gul, Sana; Lo, Kong Mun; Ul-Haq, Zaheer; Shah, Syed Adnan Ali; Ahmad, Syahida

2015-04-01

Browning of fruits and vegetables is a serious issue in the food industry, as it damages the organoleptic properties of the final products. Overproduction of melanin causes aesthetic problems such as melisma, freckles and lentigo. In this study, a series of chalcones (1-10) have been synthesized and examined for their tryrosinase inhibitory activity. The results showed that flavokawain B (1), flavokawain A (2) and compound 3 were found to be potential tyrosinase inhibitors, indicating IC50 14.20-14.38 μM values. This demonstrates that 4-substituted phenolic compound especially at ring A exhibited significant tyrosinase inhibition. Additionally, molecular docking results showed a strong binding affinity for compounds 1-3 through chelation between copper metal and ligands. The detailed molecular docking and SARs studies correlate well with the tyrosinase inhibition studies in vitro. The structures of these compounds were elucidated by the 1D and 2D NMR spectroscopy, mass spectrometry and single X-ray crystallographic techniques. These findings could lead to design and discover of new tyrosinase inhibitors to control the melanine overproduction and overcome the economic loss of food industry.

The chalcone flavokawain B induces G2/M cell-cycle arrest and apoptosis in human oral carcinoma HSC-3 cells through the intracellular ROS generation and downregulation of the Akt/p38 MAPK signaling pathway.

PubMed

Hseu, You-Cheng; Lee, Meng-Shiou; Wu, Chi-Rei; Cho, Hsin-Ju; Lin, Kai-Yuan; Lai, Guan-Hua; Wang, Sheng-Yang; Kuo, Yueh-Hsiung; Kumar, K J Senthil; Yang, Hsin-Ling

2012-03-07

Chalcones have been described to represent cancer chemopreventive food components that are rich in fruits and vegetables. In this study, we examined the anti-oral cancer effect of flavokawain B (FKB), a naturally occurring chalcone isolated from Alpinia pricei (shell gingers), and revealed its molecular mechanism of action. Treatment of human oral carcinoma (HSC-3) cells with FKB (1.25-10 μg/mL; 4.4-35.2 μM) inhibited cell viability and caused G(2)/M arrest through reductions in cyclin A/B1, Cdc2, and Cdc25C levels. Moreover, FKB treatment resulted in the induction of apoptosis, which was associated with DNA fragmentation, mitochondria dysfunction, cytochrome c and AIF release, caspase-3 and caspase-9 activation, and Bcl-2/Bax dysregulation. Furthermore, increased Fas activity and procaspase-8, procaspase-4, and procaspase-12 cleavages were accompanied by death receptor and ER-stress, indicating the involvement of mitochondria, death-receptor, and ER-stress signaling pathways. FKB induces apoptosis through ROS generation as evidenced by the upregulation of oxidative-stress markers HO-1/Nrf2. This mechanism was further confirmed by the finding that the antioxidant N-acetylcysteine (NAC) significantly blocked ROS generation and consequently inhibited FKB-induced apoptosis. Moreover, FKB downregulated the phosphorylation of Akt and p38 MAPK, while their inhibitors LY294002 and SB203580, respectively, induced G(2)/M arrest and apoptosis. The profound reduction in cell number was observed in combination treatment with FKB and Akt/p38 MAPK inhibitors, indicating that the disruption of Akt and p38 MAPK cascades plays a functional role in FKB-induced G(2)/M arrest and apoptosis in HSC-3 cells.

Molecular and functional characterization of two isoforms of chalcone synthase and their expression analysis in relation to flavonoid constituents in Grewia asiatica L

PubMed Central

Wani, Tareq A.; Pandith, Shahzad A.; Gupta, Ajai P.; Chandra, Suresh; Sharma, Namrata

2017-01-01

Chalcone synthase constitutes a functionally diverse gene family producing wide range of flavonoids by catalyzing the initial step of the phenylpropanoid pathway. There is a pivotal role of flavonoids in pollen function as they are imperative for pollen maturation and pollen tube growth during sexual reproduction in flowering plants. Here we focused on medicinally important fruit-bearing shrub Grewia asiatica. It is a rich repository of flavonoids. The fruits are highly acclaimed for various putative health benefits. Despite its importance, full commercial exploitation is hampered due to two drawbacks which include short shelf life of its fruits and larger seed volume. To circumvent these constraints, seed abortion is one of the viable options. Molecular interventions tested in a number of economic crops have been to impair male reproductive function by disrupting the chalcone synthase (CHS) gene activity. Against this backdrop the aim of the present study included cloning and characterization of two full-length cDNA clones of GaCHS isoforms from the CHS multigene family. These included GaCHS1 (NCBI acc. KX129910) and GaCHS2 (NCBI acc. KX129911) with an ORF of 1176 and 1170 bp, respectively. GaCHSs were heterologously expressed and purified in E. coli to validate their functionality. Functionality of CHS isoforms was also characterized via enzyme kinetic studies using five different substrates. We observed differential substrate specificities in terms of their Km and Vmax values. Accumulation of flavonoid constituents naringenin and quercetin were also quantified and their relative concentrations corroborated well with the expression levels of GaCHSs. Further, our results demonstrate that GaCHS isoforms show differential expression patterns at different reproductive phenological stages. Transcript levels of GaCHS2 were more than its isoform GaCHS1 at the anthesis stage of flower development pointing towards its probable role in male reproductive maturity. PMID:28662128

A novel chalcone derivative attenuates the diabetes-induced renal injury via inhibition of high glucose-mediated inflammatory response and macrophage infiltration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fang, Qilu; Zhao, Leping; Wang, Yi

Inflammation plays a central role in the development and progression of diabetic nephropathy (DN). Researches on novel anti-inflammatory agents may offer new opportunities for the treatment of DN. We previously found a chalcone derivative L6H21 could inhibit LPS-induced cytokine release from macrophages. The aim of this study was to investigate whether L6H21 could ameliorate the high glucose-mediated inflammation in NRK-52E cells and attenuate the inflammation-mediated renal injury. According to the results, L6H21 showed a great inhibitory effect on the expression of pro-inflammatory cytokines, cell adhesion molecules, chemokines, and macrophage adhesion via down-regulation of NF-κB/MAPKs activity in high glucose-stimulated renal NRK-52Emore » cells. Further, in vivo oral administration with L6H21 at a dosage of 20 mg/kg/2 days showed a decreased expression of pro-inflammatory cytokines, cell adhesion molecules, which subsequently contributed to the inhibition on renal macrophage infiltration, the reduction of serum creatinine and BUN levels, and the improvement on the fibrosis and pathological changes in the renal tissues of diabetic mice. These findings provided that chalcone derived L6H21 may be a promising anti-inflammatory agent and have the potential in the therapy of diabetic nephropathy, and importantly, MAPK/NF-κB signaling system may be a novel therapeutic target for human DN in the future. - Highlights: • Inflammation plays a central role in the development of diabetic nephropathy. • Compound L6H21 reduced the high glucose-mediated inflammation in NRK-52E cells. • Compound L6H21 attenuated the inflammation-mediated renal injury. • L6H21 exhibited anti-inflammatory effects via inactivation of NF-κB/MAPKs. • MAPKs/NF-κB may be a novel therapeutic target in diabetic nephropathy treatment.« less

Antiestrogenic activity of flavnoid phytochemicals mediated via c-Jun N-terminal protein kinase pathway. Cell-type specific regulation of estrogen receptor alpha

USDA-ARS?s Scientific Manuscript database

Flavonoid phytochemicals act as both agonists and antagonists of the human estrogen receptors (ERs). While a number of these compounds act by directly binding to the ER, certain phytochemicals, such as the flavonoid compounds chalcone and flavone, elicit antagonistic effects on estrogen signaling in...

Cs₂CO₃-Initiated Trifluoro-Methylation of Chalcones and Ketones for Practical Synthesis of Trifluoromethylated Tertiary Silyl Ethers.

PubMed

Dong, Cheng; Bai, Xing-Feng; Lv, Ji-Yuan; Cui, Yu-Ming; Cao, Jian; Zheng, Zhan-Jiang; Xu, Li-Wen

2017-05-18

It was found that 1,2-trifluoromethylation reactions of ketones, enones, and aldehydes were easily accomplished using the Prakash reagent in the presence of catalytic amounts of cesium carbonate, which represents an experimentally convenient, atom-economic process for this anionic trifluoromethylation of non-enolisable aldehydes and ketones.

Synthesis and insect antifeedant activities of some substituted styryl 3,4-dichlorophenyl ketones

NASA Astrophysics Data System (ADS)

Thirunarayanan, G.; Surya, S.; Srinivasan, S.; Vanangamudi, G.; Sathiyendiran, V.

2010-01-01

Sixteen substituted styryl 3,4-dichlorophenyl ketones [ (2E)-1-(3,4-dichlorophenyl)-3-phenyl-2-propen-1-ones] were synthesized using eco-friendly benign stereoselective crossed-aldol reaction. They are characterized by their analytical, infrared, NMR and mass spectral data. The insect antifeedant activities of these chalcones were evaluated using Caster semilooper and Achoea janata L.

In Vitro Activities of Panduratin A against Clinical Staphylococcus Strains▿

PubMed Central

Rukayadi, Yaya; Lee, Kwanghyung; Han, Sunghwa; Yong, Dongeun; Hwang, Jae-Kwan

2009-01-01

In vitro antistaphylococcal activities of panduratin A, a natural chalcone compound isolated from Kaempferia pandurata Roxb, were compared to those of commonly used antimicrobials against clinical staphylococcal isolates. Panduratin A had a MIC at which 90% of bacteria were inhibited of 1 μg/ml for clinical staphylococcal isolates and generally was more potent than commonly used antimicrobials. PMID:19651906

Phytoalexin Induction in French Bean 1

PubMed Central

Dixon, Richard A.; Dey, Prakash M.; Lawton, Michael A.; Lamb, Christopher J.

1983-01-01

Treatment of hypocotyl sections or cell suspension cultures of dwarf French bean (Phaseolus vulgaris L.) with an abiotic elicitor (denatured ribonuclease A) resulted in increased extractable activity of the enzyme l-phenylalanine ammonia-lyase. This induction could be transmitted from treated cells through a dialysis membrane to cells which were not in direct contact with the elicitor. In hypocotyl sections, induction of isoflavonoid phytoalexin accumulation was also transmitted across a dialysis membrane, although levels of insoluble, lignin-like phenolic material remained unchanged in elicitor-treated and control sections. In bean cell suspension cultures, the induction of phenylalanine ammonia-lyase in cells separated from ribonuclease-treated cells by a dialysis membrane was also accompanied by increases in the activities of chalcone synthase and chalcone isomerase, two enzymes previously implicated in the phytoalexin defense response. Such intercellular transmission of elicitation did not occur in experiments with cells treated with a biotic elicitor preparation heat-released from the cell walls of the bean pathogen Colletotrichum lindemuthianum. The results confirm and extend previous suggestions that a low molecular weight, diffusible factor of host plant origin is involved (in French bean) in the intercellular transmission of the elicitation response to abiotic elicitors. PMID:16662813

Spectral, biological screening of metal chelates of chalcone based Schiff bases of N-(3-aminopropyl) imidazole.

PubMed

Kalanithi, M; Rajarajan, M; Tharmaraj, P; Sheela, C D

2012-02-15

Tridentate chelate complexes of Co(II), Ni(II), Cu(II) and Zn(II) have been synthesized from the chalcone based ligands 2-[1-(3-(1H-imidazol-1-yl)propylimino)-3-(phenylallyl)]phenol(HL(1)), 2-[1-(3-(1H-imidazol-1-yl)propylimino)-3-p-tolylallyl]phenol(HL(2)), 2-[1-(3-(1H-imidazol-1-yl)propylimino)-3-4-nitrophenylallyl]phenol(HL(3)). Microanalytical data, UV-vis spectrophotometric method, magnetic susceptibility measurements, IR, 1H NMR, Mass, and EPR techniques were used to characterize the structure of chelates. The electronic absorption spectra and magnetic susceptibility measurements suggest a distorted square planar geometry for the copper(II) ion. The other metal complexes show distorted tetrahedral geometry. The coordination of the ligands with metal(II) ions was further confirmed by solution fluorescence spectrum. The antimicrobial activity of the ligands and metal(II) complexes against the species Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, Bacillus subtilis, Candida albigans and Aspergillus niger has been carried out and compared. The electrochemical behavior of copper(II) complex is studied by cyclic voltammetry. Copyright © 2011 Elsevier B.V. All rights reserved.

Identification of a core set of rhizobial infection genes using data from single cell-types.

PubMed

Chen, Da-Song; Liu, Cheng-Wu; Roy, Sonali; Cousins, Donna; Stacey, Nicola; Murray, Jeremy D

2015-01-01

Genome-wide expression studies on nodulation have varied in their scale from entire root systems to dissected nodules or root sections containing nodule primordia (NP). More recently efforts have focused on developing methods for isolation of root hairs from infected plants and the application of laser-capture microdissection technology to nodules. Here we analyze two published data sets to identify a core set of infection genes that are expressed in the nodule and in root hairs during infection. Among the genes identified were those encoding phenylpropanoid biosynthesis enzymes including Chalcone-O-Methyltransferase which is required for the production of the potent Nod gene inducer 4',4-dihydroxy-2-methoxychalcone. A promoter-GUS analysis in transgenic hairy roots for two genes encoding Chalcone-O-Methyltransferase isoforms revealed their expression in rhizobially infected root hairs and the nodule infection zone but not in the nitrogen fixation zone. We also describe a group of Rhizobially Induced Peroxidases whose expression overlaps with the production of superoxide in rhizobially infected root hairs and in nodules and roots. Finally, we identify a cohort of co-regulated transcription factors as candidate regulators of these processes.

Green synthesis and anticancer potential of chalcone linked-1,2,3-triazoles.

PubMed

Yadav, Pinki; Lal, Kashmiri; Kumar, Ashwani; Guru, Santosh Kumar; Jaglan, Sundeep; Bhushan, Shashi

2017-01-27

A series of chalcone linked-1,2,3-triazoles was synthesized via cellulose supported copper nanoparticle catalyzed click reaction in water. The structures of all the compounds were analyzed by IR, NMR and Mass spectral techniques. All the synthesized products were subjected to 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity assay against a panel of four human cancer cell lines (MCF-7, MIA-Pa-Ca-2, A549, HepG2) to check their anticancer potential. Compound 6h was found to be most active against all the tested cancer cell lines with IC 50 values in the range of 4-11 μM and showed better or comparable activity to the reference drug against all the tested cell lines. Cell cycle analysis revealed that compound 6h induces apoptosis and G2/S arrest in MIA-Pa-Ca-2 cells. Compound 6h triggers mitochondrial potential loss in pancreatic cancer MIA-Pa-Ca-2 cells. Further, Compound 6h also triggers caspase-3 and PARP-1 cleavage, which increases in dose dependent manner. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Inducible in vivo DNA footprints define sequences necessary for UV light activation of the parsley chalcone synthase gene.

PubMed Central

Schulze-Lefert, P; Dangl, J L; Becker-André, M; Hahlbrock, K; Schulz, W

1989-01-01

We began characterization of the protein--DNA interactions necessary for UV light induced transcriptional activation of the gene encoding chalcone synthase (CHS), a key plant defense enzyme. Three light dependent in vivo footprints appear on a 90 bp stretch of the CHS promoter with a time course correlated with the onset of CHS transcription. We define a minimal light responsive promoter by functional analysis of truncated CHS promoter fusions with a reporter gene in transient expression experiments in parsley protoplasts. Two of the three footprinted sequence 'boxes' reside within the minimal promoter. Replacement of 10 bp within either of these 'boxes' leads to complete loss of light responsiveness. We conclude that these sequences define the necessary cis elements of the minimal CHS promoter's light responsive element. One of the functionally defined 'boxes' is homologous to an element implicated in regulation of genes involved in photosynthesis. These data represent the first example in a plant defense gene of an induced change in protein--DNA contacts necessary for transcriptional activation. Also, our data argue strongly that divergent light induced biosynthetic pathways share common regulatory units. Images PMID:2566481

Molecular structure, Hirshfeld surface analysis, theoretical investigations and nonlinear optical properties of a novel crystalline chalcone derivative: (E)-1-(5-bromothiophen-2-yl)-3-(p-tolyl)prop-2-en-1-one

NASA Astrophysics Data System (ADS)

Pramodh, B.; Lokanath, N. K.; Naveen, S.; Naresh, P.; Ganguly, S.; Panda, J.

2018-06-01

In the present work, the crystal structure of a novel chalcone derivative, (E)-1-(5-bromothiophen-2-yl)-3-(p-tolyl) prop-2-en-1-one has been confirmed by X-ray diffraction studies. Hirshfeld surface analysis was carried out to explore the intermolecular interactions. From the Hirshfeld surface analysis it was observed that H⋯H (26.7%) and C⋯H (26.3%) are the major contributors to the intermolecular interactions which stabilizes the crystal structure. The coordinates were optimized using the density functional theory (DFT) calculations using B3LYP hybrid functions with 6-31G(d) basis set. The structural parameters obtained from XRD studies compliment with those calculated using DFT calculations. The HOMO and LUMO energy gap was found to be 4.1778 eV. The molecular electrostatic potential (MEP) was plotted to identify the possible reactions sites of the molecule. Further, non-linear optical (NLO) properties were investigated by calculating hyperpolarizabilities which indicate that the title compound would be a potential candidate for the NLO applications.

Enhanced pinocembrin production in Escherichia coli by regulating cinnamic acid metabolism

PubMed Central

Cao, Weijia; Ma, Weichao; Wang, Xin; Zhang, Bowen; Cao, Xun; Chen, Kequan; Li, Yan; Ouyang, Pingkai

2016-01-01

Microbial biosynthesis of pinocembrin is of great interest in the area of drug research and human healthcare. Here we found that the accumulation of the pathway intermediate cinnamic acid adversely affected pinocembrin production. Hence, a stepwise metabolic engineering strategy was carried out aimed at eliminating this pathway bottleneck and increasing pinocembrin production. The screening of gene source and the optimization of gene expression was first employed to regulate the synthetic pathway of cinnamic acid, which showed a 3.53-fold increase in pinocembrin production (7.76 mg/L) occurred with the alleviation of cinnamic acid accumulation in the engineered E. coli. Then, the downstream pathway that consuming cinnamic acid was optimized by the site-directed mutagenesis of chalcone synthase and cofactor engineering. S165M mutant of chalcone synthase could efficiently improve the pinocembrin production, and allowed the product titer of pinocembrin increased to 40.05 mg/L coupled with the malonyl-CoA engineering. With a two-phase pH fermentation strategy, the cultivation of the optimized strain resulted in a final pinocembrin titer of 67.81 mg/L. The results and engineering strategies demonstrated here would hold promise for the titer improvement of other flavonoids. PMID:27586788

Enhanced pinocembrin production in Escherichia coli by regulating cinnamic acid metabolism.

PubMed

Cao, Weijia; Ma, Weichao; Wang, Xin; Zhang, Bowen; Cao, Xun; Chen, Kequan; Li, Yan; Ouyang, Pingkai

2016-09-02

Microbial biosynthesis of pinocembrin is of great interest in the area of drug research and human healthcare. Here we found that the accumulation of the pathway intermediate cinnamic acid adversely affected pinocembrin production. Hence, a stepwise metabolic engineering strategy was carried out aimed at eliminating this pathway bottleneck and increasing pinocembrin production. The screening of gene source and the optimization of gene expression was first employed to regulate the synthetic pathway of cinnamic acid, which showed a 3.53-fold increase in pinocembrin production (7.76 mg/L) occurred with the alleviation of cinnamic acid accumulation in the engineered E. coli. Then, the downstream pathway that consuming cinnamic acid was optimized by the site-directed mutagenesis of chalcone synthase and cofactor engineering. S165M mutant of chalcone synthase could efficiently improve the pinocembrin production, and allowed the product titer of pinocembrin increased to 40.05 mg/L coupled with the malonyl-CoA engineering. With a two-phase pH fermentation strategy, the cultivation of the optimized strain resulted in a final pinocembrin titer of 67.81 mg/L. The results and engineering strategies demonstrated here would hold promise for the titer improvement of other flavonoids.

Benzofuran-chalcone hybrids as potential multifunctional agents against Alzheimer's disease: synthesis and in vivo studies with transgenic Caenorhabditis elegans.

PubMed

Sashidhara, Koneni V; Modukuri, Ram K; Jadiya, Pooja; Dodda, Ranga Prasad; Kumar, Manoj; Sridhar, Balasubramaniam; Kumar, Vikash; Haque, Rizwanul; Siddiqi, Mohammad Imran; Nazir, Aamir

2014-12-01

In the search for effective multifunctional agents for the treatment of Alzheimer's disease (AD), a series of novel hybrids incorporating benzofuran and chalcone fragments were designed and synthesized. These hybrids were screened by using a transgenic Caenorhabditis elegans model that expresses the human β-amyloid (Aβ) peptide. Among the hybrids investigated, (E)-3-(7-methyl-2-(4-methylbenzoyl)benzofuran-5-yl)-1-phenylprop-2-en-1-one (4 f), (E)-3-(2-benzoyl-7-methylbenzofuran-5-yl)-1-phenylprop-2-en-1-one (4 i), and (E)-3-(2-benzoyl-7-methylbenzofuran-5-yl)-1-(thiophen-2-yl)prop-2-en-1-one (4 m) significantly decreased Aβ aggregation and increased acetylcholine (ACh) levels along with the overall availability of ACh at the synaptic junction. These compounds were also found to decrease acetylcholinesterase (AChE) levels, reduce oxidative stress in the worms, lower lipid content, and to provide protection against chemically induced cholinergic neurodegeneration. Overall, the multifunctional effects of these hybrids qualify them as potential drug leads for further development in AD therapy. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The chalcone derivative Chana 1 protects against amyloid β peptide-induced oxidative stress and cognitive impairment.

PubMed

Kwak, Jieun; Kim, Mi-Jeong; Choi, Kyung-Chul; Choi, Hyo-Kyung; Jun, Woojin; Park, Hyun-Jin; Lee, Yoo-Hyun; Yoon, Ho-Geun

2012-07-01

Alzheimer's disease (AD) is the most common neurodegenerative disease to cause dementia in the elderly. Amyloid β (Aβ)-peptide induced oxidative stress causes the initiation and progression of AD. Recently, new chalcone derivatives termed the Chana series were synthesized. Among them, Chana 1 showed high free radical scavenging activity (72.5%), as measured by a DPPH (1,1-diphenyl-2-picrylhydrazyl) assay. In this study, we investigated the effect of Chana 1 against Aβ-induced cytotoxicity and cognitive deficits. Additionally, we sought to estimate the lethal dose, 50% (LD50) of Chana 1 in mice using an acute oral toxicity test. We found that Chana 1 significantly protected against Aβ-induced neuronal cell death in PC12 cells. Oral administration of Chana 1 at a dose of 50 mg/kg body weight/day significantly improved Aβ-induced learning and memory impairment in mice, as measured in Y-maze and passive avoidance tests. In acute toxicity tests, the LD50 in mice was determined to be 520.44 mg/kg body weight. The data are valuable for future studies and suggest that Chana 1 has therapeutic potential for the management of neurodegenerative disease.

Synthesis, spectral behaviour and photophysics of donor-acceptor kind of chalcones: Excited state intramolecular charge transfer and fluorescence quenching studies

NASA Astrophysics Data System (ADS)

Pannipara, Mehboobali; Asiri, Abdullah M.; Alamry, Khalid A.; Arshad, Muhammad N.; El-Daly, Samy A.

2015-02-01

The spectral and photophysical properties of two chalcones containing electron donating and accepting groups with intramolecular charge transfer characteristics were synthesized and characterized by 1H NMR, 13C NMR and X-ray crystallography. Both compounds show very strong solvent polarity dependent changes in their photophysical characteristics, namely, remarkable red shift in the emission spectra with increasing solvent polarity, large change in Stokes shift, significant reduction in the fluorescence quantum yield; indicating that the fluorescence states of these compounds are of intramolecular charge transfer (ICT) character. The solvent effect on the photophysical parameters such as singlet absorption, molar absorptivity, oscillator strength, dipole moment, fluorescence spectra, and fluorescence quantum yield of both compounds have been investigated comprehensively. For both dyes, Lippert-Mataga and Reichardt's correlations were used to estimate the difference between the excited and ground state dipole moments (Δμ). The interactions of dyes with colloidal silver nanoparticles (Ag NPs) were also studied in ethanol using steady state fluorescence quenching measurements. The fluorescence quenching data reveal that dynamic quenching and energy transfer play a major role in the fluorescence quenching of dyes by Ag NPs.

The soybean R2R3 MYB transcription factor GmMYB100 negatively regulates plant flavonoid biosynthesis.

PubMed

Yan, Junhui; Wang, Biao; Zhong, Yunpeng; Yao, Luming; Cheng, Linjing; Wu, Tianlong

2015-09-01

Soybean flavonoids, a group of important signaling molecules in plant-environment interaction, ubiquitously exist in soybean and are tightly regulated by many genes. Here we reported that GmMYB100, a gene encoding a R2R3 MYB transcription factor, is involved in soybean flavonoid biosynthesis. GmMYB100 is mainly expressed in flowers, leaves and immature embryo, and its level is decreased after pod ripening. Subcellular localization assay indicates that GmMYB100 is a nuclear protein. GmMYB100 has transactivation ability revealed by a yeast functional assay; whereas bioinformatic analysis suggests that GmMYB100 has a negative function in flavonoid biosynthesis. GmMYB100-overexpression represses the transcript levels of flavonoid-related genes in transgenic soybean hairy roots and Arabidopsis, and inhibits isoflavonoid (soybean) and flavonol (Arabidopsis) production in transgenic plants. Furthermore, the transcript levels of six flavonoid-related genes and flavonoid (isoflavonoid and flavone aglycones) accumulation are elevated in the GmMYB100-RNAi transgenic hairy roots. We also demonstrate that GmMYB100 protein depresses the promoter activities of soybean chalcone synthase and chalcone isomerase. These findings indicate that GmMYB100 is a negative regulator in soybean flavonoid biosynthesis pathway.

Chalcone Synthase (CHS) Gene Suppression in Flax Leads to Changes in Wall Synthesis and Sensing Genes, Cell Wall Chemistry and Stem Morphology Parameters

PubMed Central

Zuk, Magdalena; Działo, Magdalena; Richter, Dorota; Dymińska, Lucyna; Matuła, Jan; Kotecki, Andrzej; Hanuza, Jerzy; Szopa, Jan

2016-01-01

The chalcone synthase (CHS) gene controls the first step in the flavonoid biosynthesis. In flax, CHS down-regulation resulted in tannin accumulation and reduction in lignin synthesis, but plant growth was not affected. This suggests that lignin content and thus cell wall characteristics might be modulated through CHS activity. This study investigated the possibility that CHS affects cell wall sensing as well as polymer content and arrangement. CHS-suppressed and thus lignin-reduced plants showed significant changes in expression of genes involved in both synthesis of components and cell wall sensing. This was accompanied by increased levels of cellulose and hemicellulose. CHS-reduced flax also showed significant changes in morphology and arrangement of the cell wall. The stem tissue layers were enlarged averagely twofold compared to the control, and the number of fiber cells more than doubled. The stem morphology changes were accompanied by reduction of the crystallinity index of the cell wall. CHS silencing induces a signal transduction cascade that leads to modification of plant metabolism in a wide range and thus cell wall structure. PMID:27446124

Synthesis, structure and conformational analysis of imidazo-thiazines

NASA Astrophysics Data System (ADS)

Perjési, Pál; Sohár, Pál; Böcskei, Zsolt; Magyarfalvi, Gábor; Farkas, Ödön; Mák, Marianna

1996-04-01

BF 3·OEt 2-catalyzed reaction of chalcones (2) with imidazolidine-2-thione (1) yielded 2,3-dihydro-5,7-diaryl-7 H-imidazo[2,1- b][1,3]thiazines (3). The structure of the compounds was confirmed by MS, X-ray and NMR studies. Ab initio and semiempirical theoretical calculations were carried out to corroborate experimental findings concerning the possible conformations of the products.

New phenolic compounds from the twigs of Artocarpus heterophyllus.

PubMed

Di, X; Wang, S; Wang, B; Liu, Y; Yuan, H; Lou, H; Wang, X

2013-02-01

Two new chalcones, artocarpusins A and B (1 and 2), one new flavone, artocarpusin C (3), one new 2-arylbenzofuran derivative, artocarstilene A (4), and 15 flavonoids were isolated from the twigs of Artocarpus heterophyllus. Their structures were established on the basis of extensive spectroscopic analysis. Compounds 9 and 16 showed moderate inhibitory activity on the proliferation of the PC-3 and H460 cell lines.

Identification of Chalcones as Fasciola hepatica Cathepsin L Inhibitors Using a Comprehensive Experimental and Computational Approach

PubMed Central

Ferraro, Florencia; Merlino, Alicia; dell´Oca, Nicolás; Gil, Jorge; Tort, José F.; Gonzalez, Mercedes; Cerecetto, Hugo; Cabrera, Mauricio

2016-01-01

Background Increased reports of human infections have led fasciolosis, a widespread disease of cattle and sheep caused by the liver flukes Fasciola hepatica and Fasciola gigantica, to be considered an emerging zoonotic disease. Chemotherapy is the main control measure available, and triclabendazole is the preferred drug since is effective against both juvenile and mature parasites. However, resistance to triclabendazole has been reported in several countries urging the search of new chemical entities and target molecules to control fluke infections. Methodology/Principle Findings We searched a library of forty flavonoid derivatives for inhibitors of key stage specific Fasciola hepatica cysteine proteases (FhCL3 and FhCL1). Chalcones substituted with phenyl and naphtyl groups emerged as good cathepsin L inhibitors, interacting more frequently with two putative binding sites within the active site cleft of the enzymes. One of the compounds, C34, tightly bounds to juvenile specific FhCL3 with an IC50 of 5.6 μM. We demonstrated that C34 is a slow-reversible inhibitor that interacts with the Cys-His catalytic dyad and key S2 and S3 pocket residues, determinants of the substrate specificity of this family of cysteine proteases. Interestingly, C34 induces a reduction in NEJ ability to migrate through the gut wall and a loss of motility phenotype that leads to NEJ death within a week in vitro, while it is not cytotoxic to bovine cells. Conclusions/Significance Up to date there are no reports of in vitro screening for non-peptidic inhibitors of Fasciola hepatica cathepsins, while in general these are considered as the best strategy for in vivo inhibition. We have identified chalcones as novel inhibitors of the two main Cathepsins secreted by juvenile and adult liver flukes. Interestingly, one compound (C34) is highly active towards the juvenile enzyme reducing larval ability to penetrate the gut wall and decreasing NEJ´s viability in vitro. These findings open new avenues for the development of novel agents to control fluke infection and possibly other helminthic diseases. PMID:27463369

Aromatic derivatives of 1H-2,3-dihydropyrazolo(4,5-b)-1,5-diazepine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Orlov, V.D.; Kiroga, Kh.; Kolos, N.N.

1987-09-01

Aromatic derivatives of 1H-2,3-dihydropyrazole(4,5-b)-1,5-diazepine were obtained by the reaction of 1-phenyl-3-methyl-4,5-diaminopyrazole with chalcones and acetylarenes, catalyzed by acetic or sulfuric acid. The seven-membered ring in these compounds has a conformation of the boat type. The IR, UV, PMR, and mass spectra of the compounds are discussed.

Transient Silencing of CHALCONE SYNTHASE during Fruit Ripening Modifies Tomato Epidermal Cells and Cuticle Properties1[C][W

PubMed Central

España, Laura; Heredia-Guerrero, José A.; Reina-Pinto, José J.; Fernández-Muñoz, Rafael; Heredia, Antonio; Domínguez, Eva

2014-01-01

Tomato (Solanum lycopersicum) fruit ripening is accompanied by an increase in CHALCONE SYNTHASE (CHS) activity and flavonoid biosynthesis. Flavonoids accumulate in the cuticle, giving its characteristic orange color that contributes to the eventual red color of the ripe fruit. Using virus-induced gene silencing in fruits, we have down-regulated the expression of SlCHS during ripening and compared the cuticles derived from silenced and nonsilenced regions. Silenced regions showed a pink color due to the lack of flavonoids incorporated to the cuticle. This change in color was accompanied by several other changes in the cuticle and epidermis. The epidermal cells displayed a decreased tangential cell width; a decrease in the amount of cuticle and its main components, cutin and polysaccharides, was also observed. Flavonoids dramatically altered the cuticle biomechanical properties by stiffening the elastic and viscoelastic phase and by reducing the ability of the cuticle to deform. There seemed to be a negative relation between SlCHS expression and wax accumulation during ripening that could be related to the decreased cuticle permeability to water observed in the regions silencing SlCHS. A reduction in the overall number of ester linkages present in the cutin matrix was also dependent on the presence of flavonoids. PMID:25277718

The Influence of Glycosylation of Natural and Synthetic Prenylated Flavonoids on Binding to Human Serum Albumin and Inhibition of Cyclooxygenases COX-1 and COX-2.

PubMed

Tronina, Tomasz; Strugała, Paulina; Popłoński, Jarosław; Włoch, Aleksandra; Sordon, Sandra; Bartmańska, Agnieszka; Huszcza, Ewa

2017-07-21

The synthesis of different classes of prenylated aglycones (α,β-dihydroxanthohumol ( 2 ) and ( Z )-6,4'-dihydroxy-4-methoxy-7-prenylaurone ( 3 )) was performed in one step reactions from xanthohumol ( 1 )-major prenylated chalcone naturally occurring in hops. Obtained flavonoids ( 2 - 3 ) and xanthohumol ( 1 ) were used as substrates for regioselective fungal glycosylation catalyzed by two Absidia species and Beauveria bassiana . As a result six glycosides ( 4 - 9 ) were formed, of which four glycosides ( 6 - 9 ) have not been published so far. The influence of flavonoid skeleton and the presence of glucopyranose and 4- O -methylglucopyranose moiety in flavonoid molecule on binding to main protein in plasma, human serum albumin (HSA), and inhibition of cyclooxygenases COX-1 and COX-2 were investigated. Results showed that chalcone ( 1 ) had the highest binding affinity to HSA (8.624 × 10⁴ M -1 ) of all tested compounds. It has also exhibited the highest inhibition of cyclooxygenases activity, and it was a two-fold stronger inhibitor than α,β-dihydrochalcone ( 2 ) and aurone ( 3 ). The presence of sugar moiety in flavonoid molecule caused the loss of HSA binding activity as well as the decrease in inhibition of cyclooxygenases activity.

[Improving venous tone and capillary sealing. Effect of a combination of Ruscus extract and hesperidine methyl chalcone in healthy probands in heat stress].

PubMed

Rudofsky, G

1989-06-30

The drug combination of Ruscus-extract and hesperidine methyl chalcone (HMC) involves two basic mechanisms in the treatment of venous diseases: increase in venous tonicity and edema protection. This was shown in a double-blind study on 20 healthy volunteers by comparing the effectiveness of the individual substances, the combination and a placebo on the venous hemodynamics and the volume of the foot. Ruscus-extract augments the tonicity of the venous wall. This is expressed by a decrease in venous capacity (p less than 0.01), a reduction in the blood pool in the lower leg under orthostatic conditions, and a decrease in tissue volume of the foot and ankle (p less than 0.01). HMC lowers the capillary filtration rate (p less than 0.01) but augmented the blood pool. The increase in blood volume can be explained by dehydration of the tissue of the lower leg lowering the pressure of tissue on the venous system and increasing the blood pool in the limb. After administration of the combination, the blood volume was between the Ruscus and HMC volumes, while the effects on filtration rate, venous capacity and tissue volume corresponded to the changes seen after administration of HMC and Ruscus extract alone.

Phenotypic changes associated with RNA interference silencing of chalcone synthase in apple (Malus × domestica).

PubMed

Dare, Andrew P; Tomes, Sumathi; Jones, Midori; McGhie, Tony K; Stevenson, David E; Johnson, Ross A; Greenwood, David R; Hellens, Roger P

2013-05-01

We have identified in apple (Malus × domestica) three chalcone synthase (CHS) genes. In order to understand the functional redundancy of this gene family RNA interference knockout lines were generated where all three of these genes were down-regulated. These lines had no detectable anthocyanins and radically reduced concentrations of dihydrochalcones and flavonoids. Surprisingly, down-regulation of CHS also led to major changes in plant development, resulting in plants with shortened internode lengths, smaller leaves and a greatly reduced growth rate. Microscopic analysis revealed that these phenotypic changes extended down to the cellular level, with CHS-silenced lines showing aberrant cellular organisation in the leaves. Fruit collected from one CHS-silenced line was smaller than the 'Royal Gala' controls, lacked flavonoids in the skin and flesh and also had changes in cell morphology. Auxin transport experiments showed increased rates of auxin transport in a CHS-silenced line compared with the 'Royal Gala' control. As flavonoids are well known to be key modulators of auxin transport, we hypothesise that the removal of almost all flavonoids from the plant by CHS silencing creates a vastly altered environment for auxin transport to occur and results in the observed changes in growth and development. © 2013 The Authors The Plant Journal © 2013 Blackwell Publishing Ltd.

Antifungal activity of Zuccagnia punctata Cav.: evidence for the mechanism of action.

PubMed

Svetaz, Laura; Agüero, María Belén; Alvarez, Sandra; Luna, Lorena; Feresin, Gabriela; Derita, Marcos; Tapia, Alejandro; Zacchino, Susana

2007-08-01

Petroleum ether and dichloromethane extracts of fruits, aerial parts and exudate of Zuccagnia punctata Cav. (Fabaceae) showed moderate antifungal activities against the yeasts C. albicans, S. cerevisiae and C. neoformans (MICs: 62.5 - 250 microg/mL) and very strong antifungal activities against the dermatophytes M. gypseum, T. rubrum and T. mentagrophytes (MICs: 8 - 16 microg/mL) thus supporting the ethnopharmacological use of this plant. Antifungal activity-directed fractionation of active extracts by using bioautography led to the isolation of 2',4'-dihydroxy-3'-methoxychalcone (1) and 2',4'-dihydroxychalcone (2) as the compounds responsible for the antifungal activity. Second-order studies included MIC (80), MIC (50) and MFC of both chalcones in an extended panel of clinical isolates of the most sensitive fungi, and also comprised a series of targeted assays. They showed that the most active chalcone 2 is fungicidal rather than fungistatic, does not disrupt the fungal membranes up to 4 x MFC and does not act by inhibiting the fungal cell wall. So, 2',4'-dihydroxychalcone would act by a different mechanism of action than the antifungal drugs in current clinical use, such as amphotericin B, azoles or echinocandins, and thus appears to be very promising as a novel antifungal agent.

2',5'-Dihydroxychalcone down-regulates endothelial connexin43 gap junctions and affects MAP kinase activation.

PubMed

Lee, Yi-Nan; Yeh, Hung-I; Tian, Tin-Yi; Lu, Wen-Wei; Ko, Yu-Shien; Tsai, Cheng-Ho

2002-09-30

We examined the effect of 2',5'-dihydroxychalcone on connexin43 (Cx43) expression and gap-junctional communication in human umbilical vein endothelial cells (HUVEC). The result showed that expression of Cx43 is rapidly reduced by 2',5'-dihydroxychalcone in a dose-dependent manner, Concomitantly, the communication function, determined by fluorescence recovery after photobleaching (FRAP), is decreased. We further investigated whether the mitogen-activated protein (MAP) kinase and the degradation pathway of gap junctions are involved in these processes. Although the change of Cx43 is not affected by the level of fetal calf serum (FCS) used in the medium, activation of MAP kinase varies, depending on the FCS level. At a low level (0.5%), the chalcone inhibits the activation, like PD98059, a specific inhibitor of MAP kinase kinase. However, at a high level (20%), MAP kinase is activated. On the other hand, the chalcone's down-regulating effect on Cx43, while is totally blocked by protease inhibitors leupeptin and N-acetyl-leucyl-norleucinal (ALLN), persists in the presence of PD98059, We concluded that 2',5'-dihydroxychalcone down-regulates Cx43 expression and gap-junctional communication in the HUVEC via enhancement of the proteolysis pathway, and this compound possesses dual effects on MAP kinase activation.

Tetramethoxychalcone, a chalcone derivative, suppresses proliferation, blocks cell cycle progression, and induces apoptosis of human ovarian cancer cells.

PubMed

Qi, Zihao; Liu, Mingming; Liu, Yang; Zhang, Meiqin; Yang, Gong

2014-01-01

In the present study, we investigated the in vitro antitumor functions of a synthetic chalcone derivative 4,3',4',5'- tetramethoxychalcone (TMOC) in ovarian cancer cells. We found that TMOC inhibited the proliferation and colony formation of cisplatin sensitive cell line A2780 and resistant cell line A2780/CDDP, as well as ovarian cancer cell line SKOV3 in a time- and dose-dependent manner. Treatment of A2780 cells with TMOC resulted in G0/G1 cell cycle arrest through the down-regulation of cyclin D1 and CDK4, and the up-regulation of p16, p21 and p27 proteins. We demonstrated that TMOC might induce cell apoptosis through suppressing Bcl-2 and Bcl-xL, but enhancing the expression of Bax and the cleavage of PARP-1. Treatment of TMOC also reduced the invasion and migration of A2780 cells. Finally, we found that TMOC inhibited the constitutive activation of STAT3 signaling pathway and induced the expression of the tumor suppressor PTEN regardless of the p53 status in cell lines. These data suggest that TMOC may be developed as a potential chemotherapeutic agent to effectively treat certain cancers including ovarian cancer.

Synthesis of different heterocycles-linked chalcone conjugates as cytotoxic agents and tubulin polymerization inhibitors.

PubMed

Shankaraiah, Nagula; Nekkanti, Shalini; Brahma, Uma Rani; Praveen Kumar, Niggula; Deshpande, Namrata; Prasanna, Daasi; Senwar, Kishna Ram; Jaya Lakshmi, Uppu

2017-09-01

A series of new heterocycles-linked chalcone conjugates has been designed and synthesized by varying different alkane spacers. These conjugates were tested for their in vitro cytotoxic potential against a panel of selected human cancer cell lines namely, lung (A549 and NCI-H460), prostate (DU-145 and PC-3), colon (HCT-15 and HCT-116), and brain (U-87 glioblastoma) by MTT assay. Notably, among all the tested compounds, 4a exhibited potent cytotoxicity on NCI-H460 (lung cancer) cells with IC 50 of 1.48±0.19µM. The compound 4a showed significant inhibition of tubulin polymerization and disruption of the formation of microtubules (IC 50 of 9.66±0.06μM). Moreover, phase contrast microscopy and DAPI staining studies indicated that compound 4a can induce apoptosis in NCI-H460 cells. Further, the flow-cytometry analysis revealed that compound 4a arrests NCI-H460 cells in the G2/M phase of the cell cycle. In addition, molecular docking studies of the most active compounds 4a and 4b into the colchicine site of the tubulin, revealed the possible mode of interaction by these new conjugates. Copyright © 2017 Elsevier Ltd. All rights reserved.

Tetramethoxychalcone, a Chalcone Derivative, Suppresses Proliferation, Blocks Cell Cycle Progression, and Induces Apoptosis of Human Ovarian Cancer Cells

PubMed Central

Liu, Yang; Zhang, Meiqin; Yang, Gong

2014-01-01

In the present study, we investigated the in vitro antitumor functions of a synthetic chalcone derivative 4,3′,4′,5′- tetramethoxychalcone (TMOC) in ovarian cancer cells. We found that TMOC inhibited the proliferation and colony formation of cisplatin sensitive cell line A2780 and resistant cell line A2780/CDDP, as well as ovarian cancer cell line SKOV3 in a time- and dose-dependent manner. Treatment of A2780 cells with TMOC resulted in G0/G1 cell cycle arrest through the down-regulation of cyclin D1 and CDK4, and the up-regulation of p16, p21 and p27 proteins. We demonstrated that TMOC might induce cell apoptosis through suppressing Bcl-2 and Bcl-xL, but enhancing the expression of Bax and the cleavage of PARP-1. Treatment of TMOC also reduced the invasion and migration of A2780 cells. Finally, we found that TMOC inhibited the constitutive activation of STAT3 signaling pathway and induced the expression of the tumor suppressor PTEN regardless of the p53 status in cell lines. These data suggest that TMOC may be developed as a potential chemotherapeutic agent to effectively treat certain cancers including ovarian cancer. PMID:25180593

Synthesis, characterization and biological activities of some Ru(II) complexes with substituted chalcones and their applications as chemotherapeutics against breast cancer

NASA Astrophysics Data System (ADS)

Singh, Ashok K.; Saxena, Gunjan; Dixit, Shivani; Hamidullah; Singh, Sachin K.; Singh, Sudheer K.; Arshad, M.; Konwar, Rituraj

2016-05-01

Four new Ru(II) DMSO complexes with substituted chalcone ligands viz. (E)-1-(2-hydroxyphenyl)-3-(4-methoxyphenyl)prop-2-en-1-one (HL1), (E)-1-(2-hydroxyphenyl)-3-(4-nitrophenyl)prop-2-en-1-one (HL2), (E)-3-(4-(dimethylamino)phenyl)-1-(2-hydroxyphenyl)prop-2-en-1-one (HL3) and (E)-1-(2-hydroxyphenyl)-3-(4-Chlorophenyl)prop-2-en-1-one (HL4) have been synthesized, and characterized by micro-analyses, IR, 1H NMR, UV-Vis and ESI-MS and screened for anti-cancer activity against breast cancer cell lines (MCF-7 and MDA MB-231). Compounds HL4 and [Ru(HL1) (O-DMSO)3(S-DMSO)]Cl (M1R) showed significant anti-breast cancer activity as evident from cytotoxicity, morphological and nuclear changes, DNA fragmentation and cell cycle arrest in breast cancer cells. UV-Vis and CD-spectra analysis showed HL4 and M1R interfered with DNA absorption spectra possibly due to DNA binding whereas these compounds were devoid of DNA topoisomerase inhibiting activity. Thus, these Ru(II) compounds have been established as new leads for future optimization by improving anti-cancer potency and safety.

Synthesis and evaluation of ethyleneoxylated and allyloxylated chalcone derivatives for imaging of amyloid β plaques by SPECT.

PubMed

Fuchigami, Takeshi; Yamashita, Yuki; Haratake, Mamoru; Ono, Masahiro; Yoshida, Sakura; Nakayama, Morio

2014-05-01

We report radioiodinated chalcone derivatives as new SPECT imaging probes for amyloid β (Aβ) plaques. The monoethyleneoxy derivative 2 and allyloxy derivative 8 showed a high affinity for Aβ(1-42) aggregates with Ki values of 24 and 4.5 nM, respectively. Fluorescent imaging demonstrated that 2 and 8 clearly stained thioflavin-S positive Aβ plaques in the brain sections of Tg2576 transgenic mice. In vitro autoradiography revealed that [(125)I]2 displayed no clear accumulation toward Aβ plaques in the brain sections of Tg2576 mice, whereas the accumulation pattern of [(125)I]8 matched with the presence of Aβ plaques both in the brain sections of Tg2576 mice and an AD patient. In biodistribution studies using normal mice, [(125)I]2 showed preferable in vivo pharmacokinetics (4.82%ID/g at 2 min and 0.45%ID/g at 60 min), while [(125)I]8 showed only a modest brain uptake (1.62%ID/g at 2 min) with slow clearance (0.56%ID/g at 60 min). [(125)I]8 showed prospective binding properties for Aβ plaques, although further structural modifications are needed to improve the blood brain barrier permeability and washout from brain. Copyright © 2014 Elsevier Ltd. All rights reserved.

Cis-regulatory Evolution of Chalcone-Synthase Expression in the Genus Arabidopsis

PubMed Central

de Meaux, Juliette; Pop, A.; Mitchell-Olds, T.

2006-01-01

The contribution of cis-regulation to adaptive evolutionary change is believed to be essential, yet little is known about the evolutionary rules that govern regulatory sequences. Here, we characterize the short-term evolutionary dynamics of a cis-regulatory region within and among two closely related species, A. lyrata and A. halleri, and compare our findings to A. thaliana. We focused on the cis-regulatory region of chalcone synthase (CHS), a key enzyme involved in the synthesis of plant secondary metabolites. We observed patterns of nucleotide diversity that differ among species but do not depart from neutral expectations. Using intra- and interspecific F1 progeny, we have evaluated functional cis-regulatory variation in response to light and herbivory, environmental cues, which are known to induce CHS expression. We find that substantial cis-regulatory variation segregates within and among populations as well as between species, some of which results from interspecific genetic introgression. We further demonstrate that, in A. thaliana, CHS cis-regulation in response to herbivory is greater than in A. lyrata or A. halleri. Our work indicates that the evolutionary dynamics of a cis-regulatory region is characterized by pervasive functional variation, achieved mostly by modification of response modules to one but not all environmental cues. Our study did not detect the footprint of selection on this variation. PMID:17028316

Genome-Wide Identification, Characterization and Expression Analysis of the Chalcone Synthase Family in Maize

PubMed Central

Han, Yahui; Ding, Ting; Su, Bo; Jiang, Haiyang

2016-01-01

Members of the chalcone synthase (CHS) family participate in the synthesis of a series of secondary metabolites in plants, fungi and bacteria. The metabolites play important roles in protecting land plants against various environmental stresses during the evolutionary process. Our research was conducted on comprehensive investigation of CHS genes in maize (Zea mays L.), including their phylogenetic relationships, gene structures, chromosomal locations and expression analysis. Fourteen CHS genes (ZmCHS01–14) were identified in the genome of maize, representing one of the largest numbers of CHS family members identified in one organism to date. The gene family was classified into four major classes (classes I–IV) based on their phylogenetic relationships. Most of them contained two exons and one intron. The 14 genes were unevenly located on six chromosomes. Two segmental duplication events were identified, which might contribute to the expansion of the maize CHS gene family to some extent. In addition, quantitative real-time PCR and microarray data analyses suggested that ZmCHS genes exhibited various expression patterns, indicating functional diversification of the ZmCHS genes. Our results will contribute to future studies of the complexity of the CHS gene family in maize and provide valuable information for the systematic analysis of the functions of the CHS gene family. PMID:26828478

Low Temperature Induces the Accumulation of Phenylalanine Ammonia-Lyase and Chalcone Synthase mRNAs of Arabidopsis thaliana in a Light-Dependent Manner.

PubMed Central

Leyva, A.; Jarillo, J. A.; Salinas, J.; Martinez-Zapater, J. M.

1995-01-01

Anthocyanins, which accumulate in leaves and stems in response to low temperature and changes in light intensity, are synthesized through the phenylpropanoid pathway that is controlled by key enzymes that include phenylalanine ammonia-lyase (PAL) and chalcone synthase (CHS). In this work we demonstrate that PAL and CHS mRNAs accumulate in leaves of Arabidopsis thaliana (L.) Heynh. upon exposure to low temperature in a light-dependent manner. The regulation of the PAL1 gene expression by low temperature and light was examined by analyzing the expression of the [beta]-glucuronidase (uidA) reporter gene in transgenic Arabidopsis plants containing the uidA gene of Escherichia coli under the control of the PAL1 promoter. The results indicate that the accumulation of PAL1 mRNA is transcriptionally regulated. Histochemical staining for [beta]-glucuronidase activity showed that the PAL1 promoter is preferentially activated in photosynthetically active cells, paralleling anthocyanin accumulation. Moreover, we show that light may also be implicated in the regulation of the CHS gene in response to bacterial infiltration. Finally, using two transparent testa Arabidopsis mutants that are unable to accumulate anthocyanins, we demonstrate that these pigments are not required for successful development of freezing tolerance in this species. PMID:12228452

Autophagy-mediated degradation of IAPs and c-FLIP L potentiates apoptosis induced by combination of TRAIL and Chal-24

DOE PAGES

Xu, Jennings; Xu, Xiuling; Shi, Shaoqing; ...

2015-11-02

Combination chemotherapy is an effective strategy for increasing anticancer efficacy, reducing side effects and alleviating drug resistance. In this paper, we report that combination of the recently identified novel chalcone derivative, chalcone-24 (Chal-24), and TNF-related apoptosis-inducing ligand (TRAIL) significantly increases cytotoxicity in lung cancer cells. Chal-24 treatment significantly enhanced TRAIL-induced activation of caspase-8 and caspase-3, and the cytotoxicity induced by combination of these agents was effectively suppressed by the pan-caspase inhibitor z-VAD-fmk. Chal-24 and TRAIL combination suppressed expression of cellular FLICE (FADD-like IL-1β-converting enzyme)-inhibitory protein large (c-FLIPL) and cellular inhibitor of apoptosis proteins (c-IAPs), and ectopic expression of c-FLIPL andmore » c-IAPs inhibited the potentiated cytotoxicity. In addition, TRAIL and Chal-24 cooperatively activated autophagy. Suppression of autophagy effectively attenuated cytotoxicity induced by Chal-24 and TRAIL combination, which was associated with attenuation of c-FLIPL and c-IAPs degradation. In conclusion, these results suggest that Chal-24 potentiates the anticancer activity of TRAIL through autophagy-mediated degradation of c-FLIPL and c-IAPs, and that combination of Chal-24 and TRAIL could be an effective approach in improving chemotherapy efficacy.« less

Accumulation of kaempferitrin and expression of phenyl-propanoid biosynthetic genes in kenaf (Hibiscus cannabinus).

PubMed

Zhao, Shicheng; Li, Xiaohua; Cho, Dong Ha; Arasu, Mariadhas Valan; Al-Dhabi, Naif Abdullah; Park, Sang Un

2014-10-23

Kenaf (Hibiscus cannabinus) is cultivated worldwide for its fiber; however, the medicinal properties of this plant are currently attracting increasing attention. In this study, we investigated the expression levels of genes involved in the biosynthesis of kaempferitrin, a compound with many biological functions, in different kenaf organs. We found that phenylalanine ammonia lyase (HcPAL) was more highly expressed in stems than in other organs. Expression levels of cinnamate 4-hydroxylase (HcC4H) and 4-coumarate-CoA ligase (Hc4CL) were highest in mature leaves, followed by stems and young leaves, and lowest in roots and mature flowers. The expression of chalcone synthase (HcCHS), chalcone isomerase (HcCHI), and flavone 3-hydroxylase (HcF3H) was highest in young flowers, whereas that of flavone synthase (HcFLS) was highest in leaves. An analysis of kaempferitrin accumulation in the different organs of kenaf revealed that the accumulation of this compound was considerably higher (>10-fold) in leaves than in other organs. On the basis of a comparison of kaempferitrin contents with the expression levels of different genes in different organs, we speculate that HcFLS plays an important regulatory role in the kaempferitrin biosynthetic pathway in kenaf.

Exploration of (hetero)aryl derived thienylchalcones for antiviral and anticancer activities.

PubMed

Patil, Vikrant; Patil, Siddappa A; Patil, Renukadevi; Bugarin, Alejandro; Beaman, Kenneth; Patil, Shivaputra A

2018-05-23

Search for new antiviral and anticancer agents are essential because of the emergence of drug resistance in recent years. In continuation of our efforts in identifying the new small molecule antiviral and anticancer agents, we identified chalcones as potent antiviral and anticancer agents. With the aim of identifying the broad acting antiviral and anticancer agents, we discovered substituted aryl/heteroaryl derived thienyl chalcones as antiviral and anticancer agents. A focused set of thienyl chalcone derivaties II-VI was screened for selected viruses Hepatitis B virus (HBV), Herpes simplex virus 1 (HSV-1), Human cytomegalovirus (HCMV), Dengue virus 2 (DENV2), Influenza A (H1N1) virus, MERS coronavirus, Poliovirus 1 (PV 1), Rift Valley fever (RVF), Tacaribe virus (TCRV), Venezuelan equine encephalitis virus (VEE) and Zika virus (ZIKV) using the National Institute of Allergy and Infectious Diseases (NIAID)'s Division of Microbiology and Infectious Diseases (DMID) antiviral screening program. Additionally, a cyclopropylquinoline derivative IV has been screened for 60 human cancer cell lines using the Development Therapeutics Program (DTP) of NCI. All thienyl chalcone derivatives II-VI displayed moderate to excellent antiviral activity towards several viruses tested. Compounds V and VI were turned out be active compounds towards human cytomegalovirus for both normal strain (AD169) as well as resistant isolate (GDGr K17). Particularly, cyano derivative V showed very high potency (EC50: <0.05 µM) towards AD169 strain of HCMV compared to standard drug Ganciclovir (EC50: 0.12 µM). Additionally, it showed moderate activity in the secondary assay (AD169; EC50: 2.30 µM). The cyclopropylquinoline derivative IV displayed high potency towards Rift Valley fever virus (RVFV) and Tacaribe virus (TCRV). The cyclopropylquinoline derivative IV is nearly 28 times more potent in our initial in vitro visual assay (EC50: 0.39 μg/ml) and nearly 17 times more potent in neutral red assay (EC50: 0.71 μg/ml) compared to the standard drug Ribavirin (EC50: 11 μg/ml; visual assay and EC50: 12 μg/ml; neutral red assay). It is nearly 12 times more potent in our initial in vitro visual assay (EC50: >1 μg/ml) and nearly 8 times more potent in neutral red assay (EC50: >1.3 μg/ml) compared to the standard drug Ribavirin (EC50: 12 μg/ml; visual assay and EC50: 9.9 μg/ml; neutral red assay) towards Tacaribe virus (TCRV). Additionally, cyclopropylquinoline derivative IV has shown strong growth inhibitory activity towards three major cancer (colon, breast, and leukemia) cell lines and moderate growth inhibition shown towards other cancer cell lines screened. Compounds V and VI were demonstrated viral inhibition towards Human cytomegalovirus, whereas cyclopropylquinoline derivative IV towards Rift Valley fever virus and Tacaribe virus. Additionally, cyclopropylquinoline derivative IV has displayed very good cytotoxicity against colon, breast and leukemia cell lines in vitro. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

New Ferrocene Compounds as Selective Cyclooxygenase (COX-2) Inhibitors: Design, Synthesis, Cytotoxicity and Enzyme-inhibitory Activity.

PubMed

Farzaneh, Shabnam; Zeinalzadeh, Elnaz; Daraei, Bahram; Shahhosseini, Soraya; Zarghi, Afshin

2018-01-01

Due to the astonishing properties of ferrocene and its derivatives, it has a broad application in diverse areas. Numerous ferrocene derivatives demonstrated anti-proliferative activity. Also COX-2, as a key isoenzyme for production of prostaglandins, is frequently overexpressed in various cancers. It is now recognized that COX-2 over expression promotes tumorigenic functions which can be suppressed by COX-2 inhibitors, a phenomenon useful for the preventing of tumor progression. The combination of COX-2 inhibitors with other anti-cancer or cancer prevention drugs may reduce their side effects in future cancer prevention and treatment. Owing to high anticancer potential of ferrocene derivatives and considerable COX-2 inhibitory and cytotoxicity effects of our previously synthesized chalcones, we decided to incorporate the ferrocenyl moiety into appropriate COX-2 inhibitor chalcone based scaffold, to evaluate COX-2 inhibitory activity as well as anticancer activities. Chalcones were synthesized via clasien-schmidt condensation of methylsulfonyl aldehyde and acetyl ferrocene. Further different amines with solvent free and ultra sound condition were reacted with chalcones to have different 1-ferrocenyl-3-amino carbonyl compounds. Docking study was carried out with Auto Dock vina software. All the newly-synthesized compounds were evaluated for their cyclooxygenase-2 (COX-2) inhibitory activity using chemiluminescent enzyme assays as well as cytotoxicity activity against MCF-7 and T47D and fibroblast cell lines by MTT assay. In vitro COX-1/COX-2 inhibition studies demonstrated that all compounds were selective inhibitors of the COX-2 isozyme with IC50 values in the highly potent 0.05-0.12 µM range, and COX-2 selectivity indexes (SI) in the 148.3-313.7 range. These results indicated that either potency or selectivity of COX-2 inhibitory activity was affected by the nature and size of the substituents on C-3 of propane-1-one. Also anti-proliferative and toxicity activities of synthesized compounds against breast cancer cell lines MCF-7 and T47D and fibroblast cell lines showed that the synthesized compounds had mild to moderate cytotoxicity against MCT7 and T47D breast cancer cell lines at 10 µM concentration. In vitro COX-1/COX-2 inhibition studies and anticancer activity against MCF-7, identified 1-ferrocenyl-3-(4-methylsulfonylphenyl) propen-1-one as a potent compound (IC50 COX-2 = 0.05 µM, MCF-7: % inhibition (at concentration of 10 µM) = 32.7%), and also 1-ferrocenyl-3- (propan-1-amine)-3-(4-methylsulfonylphenyl) propan-1-one showed the most selectivity on COX-2 inhibition (selectivity index= 313.7). A novel group of ferrocene compounds, possessing a methyl sulfonyl COX-2 pharmacophore were synthesized to investigate the effect of different substituents on selectivity and potency of COX-2 inhibitory activity and their cytotoxicity effects. This study indicates that 1-ferrocenyl-3-amino carbonyl compounds having ferrocene motif and methyl sulfonyl COX-2 pharmacophore is a suitable scaffold to design COX-2 inhibitors and anti-cancer agents. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Antiviral and antituberculous activity of Helichrysum melanacme constituents.

PubMed

Lall, N; Hussein, A A; Meyer, J J M

2006-04-01

Bioassay guided fractionation of the acetonic extract of Helichrysum melanacme using human Influenza virus type A and a drug-sensitive strain of Mycobacterium tuberculosis in vitro resulted in the isolation of 2 4',6'-trihydroxy-3'-prenylchalcone (1) and 4',6',5''-trihydroxy-6'',6''-dimethyldihydropyrano[2'',3''-2',3'] chalcone (2) as active constituents. 3-O-methylquercetin and quercetin were also isolated but were inactive against the microorganisms tested in this study.

(2E)-3-[4-(Benz-yloxy)phen-yl]-1-(2,6-dichloro-3-fluoro-phen-yl)prop-2-en-1-one.

PubMed

Praveen, Aletti S; Yathirajan, Hemmige S; Gerber, Thomas; van Brecht, Benjamin; Betz, Richard

2012-12-01

In the title compound, C22H15Cl2FO2, a chalcone derivative featuring a threefold-halogenated aromatic substituent, the conformation about the C=C bond is E. In the crystal C-H⋯F and C-H⋯Cl contacts connect the mol-ecules into undulating sheets parallel to (101). In addition, C-H⋯π inter-actions are also present.

Molecular structure, second- and third-order nonlinear optical properties and DFT studies of a novel non-centrosymmetric chalcone derivative: (2E)-3-(4-fluorophenyl)-1-(4-{[(1E)-(4-fluorophenyl)methylene]amino}phenyl)prop-2-en-1-one

NASA Astrophysics Data System (ADS)

Maidur, Shivaraj R.; Patil, Parutagouda Shankaragouda; Ekbote, Anusha; Chia, Tze Shyang; Quah, Ching Kheng

2017-09-01

In the present work, the title chalcone, (2E)-3-(4-fluorophenyl)-1-(4-{[(1E)-(4-fluorophenyl) methylene]amino}phenyl)prop-2-en-1-one (abbreviated as FAMFC), was synthesized and structurally characterized by single-crystal X-ray diffraction. The compound is crystallized in the monoclinic system with non-centrosymmetric space group P21 and hence it satisfies the essential condition for materials to exhibit second-order nonlinear optical properties. The molecular structure was further confirmed by using FT-IR and 1H NMR spectroscopic techniques. The title crystal is transparent in the Vis-NIR region and has a direct band gap. The third-order nonlinear optical properties were investigated in solution (0.01 M) by Z-scan technique using a continuous wave (CW) DPSS laser at the wavelength of 532 nm. The title chalcone exhibited significant two-photon absorption (β = 35.8 × 10- 5 cm W- 1), negative nonlinear refraction (n2 = - 0.18 × 10- 8 cm2 W- 1) and optical limiting (OL threshold = 2.73 kJ cm- 2) under the CW regime. In support of the experimental results, a comprehensive theoretical study was carried out on the molecule of FAMFC using density functional theory (DFT). The optimized geometries and frontier molecular orbitals were calculated by employing B3LYP/6-31 + G level of theory. The optimized molecular structure was confirmed computationally by IR vibrational and 1H NMR spectral analysis. The experimental UV-Vis-NIR spectrum was interpreted using computational chemistry under time-dependent DFT. The static and dynamic NLO properties such as dipole moments (μ), polarizability (α), and first hyperpolarizabilities (β) were computed by using finite field method. The obtained dynamic first hyperpolarizability β(- 2ω;ω,ω) at input frequency ω = 0.04282 a.u. is predicted to be 161 times higher than urea standard. The electronic excitation energies and HOMO-LUMO band gap for FAMFC were also evaluated by DFT. The experimental and theoretical results are in good agreement, and the NLO study suggests that FAMFC molecule can be a potential candidate in the nonlinear optical applications.

Molecular structure, second- and third-order nonlinear optical properties and DFT studies of a novel non-centrosymmetric chalcone derivative: (2E)-3-(4-fluorophenyl)-1-(4-{[(1E)-(4-fluorophenyl)methylene]amino}phenyl)prop-2-en-1-one.

PubMed

Maidur, Shivaraj R; Patil, Parutagouda Shankaragouda; Ekbote, Anusha; Chia, Tze Shyang; Quah, Ching Kheng

2017-09-05

In the present work, the title chalcone, (2E)-3-(4-fluorophenyl)-1-(4-{[(1E)-(4-fluorophenyl) methylene]amino}phenyl)prop-2-en-1-one (abbreviated as FAMFC), was synthesized and structurally characterized by single-crystal X-ray diffraction. The compound is crystallized in the monoclinic system with non-centrosymmetric space group P2 1 and hence it satisfies the essential condition for materials to exhibit second-order nonlinear optical properties. The molecular structure was further confirmed by using FT-IR and 1 H NMR spectroscopic techniques. The title crystal is transparent in the Vis-NIR region and has a direct band gap. The third-order nonlinear optical properties were investigated in solution (0.01M) by Z-scan technique using a continuous wave (CW) DPSS laser at the wavelength of 532nm. The title chalcone exhibited significant two-photon absorption (β=35.8×10 -5 cmW -1 ), negative nonlinear refraction (n 2 =-0.18×10 -8 cm 2 W -1 ) and optical limiting (OL threshold=2.73kJcm -2 ) under the CW regime. In support of the experimental results, a comprehensive theoretical study was carried out on the molecule of FAMFC using density functional theory (DFT). The optimized geometries and frontier molecular orbitals were calculated by employing B3LYP/6-31+G level of theory. The optimized molecular structure was confirmed computationally by IR vibrational and 1 H NMR spectral analysis. The experimental UV-Vis-NIR spectrum was interpreted using computational chemistry under time-dependent DFT. The static and dynamic NLO properties such as dipole moments (μ), polarizability (α), and first hyperpolarizabilities (β) were computed by using finite field method. The obtained dynamic first hyperpolarizability β(-2ω;ω,ω) at input frequency ω=0.04282a.u. is predicted to be 161 times higher than urea standard. The electronic excitation energies and HOMO-LUMO band gap for FAMFC were also evaluated by DFT. The experimental and theoretical results are in good agreement, and the NLO study suggests that FAMFC molecule can be a potential candidate in the nonlinear optical applications. Copyright © 2017 Elsevier B.V. All rights reserved.

Combined effect of CO2 enrichment and foliar application of salicylic acid on the production and antioxidant activities of anthocyanin, flavonoids and isoflavonoids from ginger

PubMed Central

2012-01-01

Background The increase in atmospheric CO2 concentration caused by climate change and agricultural practices is likely to affect biota by producing changes in plant growth, allocation and chemical composition. This study was conducted to evaluate the combined effect of the application of salicylic acid (SA, at two levels: 0 and 10-3 M) and CO2 enrichment (at two levels: 400 and 800 μmol·mol−1) on the production and antioxidant activities of anthocyanin, flavonoids and isoflavonoids from two Malaysian ginger varieties, namely Halia Bentong and Halia Bara. Methods High-performance liquid chromatography (HPLC) with photodiode array detection and mass spectrometry was employed to identify and quantify the flavonoids and anthocyanins in the ginger extracts. The antioxidant activity of the leaf extracts was determined by the 1,1-diphenyl-2-picrylhydrazyl (DPPH) and thiobarbituric acid (TBA) assays. The substrate specificity of chalcone synthase, the key enzyme for flavonoid biosynthesis, was investigated using the chalcone synthase (CHS) assay. Results CO2 levels of 800 μmol·mol−1 significantly increased anthocyanin, rutin, naringenin, myricetin, apigenin, fisetin and morin contents in ginger leaves. Meanwhile, the combined effect of SA and CO2 enrichment enhanced anthocyanin and flavonoid production compared with single treatment effects. High anthocyanin content was observed in H Bara leaves treated with elevated CO2 and SA. The highest chalcone synthase (CHS) activity was observed in plants treated with SA and CO2 enrichment. Plants not treated with SA and kept under ambient CO2 conditions showed the lowest CHS activity. The highest free radical scavenging activity corresponded to H Bara treated with SA under high CO2 conditions, while the lowest activity corresponded to H Bentong without SA treatment and under atmospheric CO2 levels. As the level of CO2 increased, the DPPH activity increased. Higher TBA activity was also recorded in the extracts of H Bara treated with SA and grown under high CO2 conditions. Conclusions The biological activities of both ginger varieties were enhanced when the plants were treated with SA and grown under elevated CO2 concentration. The increase in the production of anthocyanin and flavonoids in plants treated with SA could be attributed to the increase in CHS activity under high CO2 levels. PMID:23176249

Combined effect of CO(2) enrichment and foliar application of salicylic acid on the production and antioxidant activities of anthocyanin, flavonoids and isoflavonoids from ginger.

PubMed

Ghasemzadeh, Ali; Jaafar, Hawa Ze; Karimi, Ehsan; Ibrahim, Mohd Hafiz

2012-11-23

The increase in atmospheric CO(2) concentration caused by climate change and agricultural practices is likely to affect biota by producing changes in plant growth, allocation and chemical composition. This study was conducted to evaluate the combined effect of the application of salicylic acid (SA, at two levels: 0 and 10-3 M) and CO(2) enrichment (at two levels: 400 and 800 μmol·mol-1) on the production and antioxidant activities of anthocyanin, flavonoids and isoflavonoids from two Malaysian ginger varieties, namely Halia Bentong and Halia Bara. High-performance liquid chromatography (HPLC) with photodiode array detection and mass spectrometry was employed to identify and quantify the flavonoids and anthocyanins in the ginger extracts. The antioxidant activity of the leaf extracts was determined by the 1,1-diphenyl-2-picrylhydrazyl (DPPH) and thiobarbituric acid (TBA) assays. The substrate specificity of chalcone synthase, the key enzyme for flavonoid biosynthesis, was investigated using the chalcone synthase (CHS) assay. CO(2) levels of 800 μmol·mol-1 significantly increased anthocyanin, rutin, naringenin, myricetin, apigenin, fisetin and morin contents in ginger leaves. Meanwhile, the combined effect of SA and CO(2) enrichment enhanced anthocyanin and flavonoid production compared with single treatment effects. High anthocyanin content was observed in H Bara leaves treated with elevated CO(2) and SA. The highest chalcone synthase (CHS) activity was observed in plants treated with SA and CO(2) enrichment. Plants not treated with SA and kept under ambient CO(2) conditions showed the lowest CHS activity. The highest free radical scavenging activity corresponded to H Bara treated with SA under high CO(2) conditions, while the lowest activity corresponded to H Bentong without SA treatment and under atmospheric CO(2) levels. As the level of CO(2) increased, the DPPH activity increased. Higher TBA activity was also recorded in the extracts of H Bara treated with SA and grown under high CO(2) conditions. The biological activities of both ginger varieties were enhanced when the plants were treated with SA and grown under elevated CO(2) concentration. The increase in the production of anthocyanin and flavonoids in plants treated with SA could be attributed to the increase in CHS activity under high CO(2) levels.

A chalcone showing positional disorder, two related diarylcyclohexenones showing enantiomeric disorder and a related hydroxyterphenyl, all derived from simple carbonyl precursors.

PubMed

Salian, Vinutha V; Narayana, Badiadka; Yathirajan, Hemmige S; Akkurt, Mehmet; Çelik, Ömer; Ersanlı, Cem Cüneyt; Glidewell, Christopher

2015-07-01

Four compounds are reported, all of which lie along a versatile reaction pathway which leads from simple carbonyl compounds to terphenyls. (2E)-1-(2,4-Dichlorophenyl)-3- [4-(prop-1-en-2-yl)phenyl]prop-2-en-1-one, C18H14Cl2O, (I), prepared from 4-(prop-1-en-2-yl)benzaldehyde and 2,4-dichloroacetophenone, exhibits disorder over two sets of atomic sites having occupancies of 0.664 (6) and 0.336 (6). The related chalcone (2E)-3-(4-chlorophenyl)-1-(4-fluorophenyl)prop-2-en-1-one reacts with acetone to produce (5RS)-3-(4-chlorophenyl)-5-[4-(propan-2-yl)phenyl]cyclohex-2-en-1-one, C21H21ClO, (II), which exhibits enantiomeric disorder with occupancies at the reference site of 0.662 (4) and 0.338 (4) for the (5R) and (5S) forms; the same chalcone reacts with methyl 3-oxobutanoate to give methyl (1RS,6SR)-4-(4-chlorophenyl)-6-[4-(propan-2-yl)phenyl]-2-oxocyclohex-3-ene-1-carboxylate, C23H23ClO3, (III), where the reference site contains both (1R,6S) and (1S,6R) forms with occupancies of 0.923 (3) and 0.077 (3), respectively. Oxidation, using 2,3-dichloro-5,6-dicyano-1,4-benzoquinone, of ethyl (1RS,6SR)-6-(4-bromophenyl)-4-(4-fluorophenyl)-2-oxocyclohex-3-ene-1-carboxylate, prepared in a similar manner to (II) and (III), produces ethyl 4''-bromo-4-fluoro-5'-hydroxy-1,1':3',1''-terphenyl-4'-carboxylate, C21H16BrFO3, (IV), which crystallizes with Z' = 2 in the space group P-1. There are no significant intermolecular interactions in the structures of compounds (I) and (II), but for the major disorder component of compound (III), the molecules are linked into sheets by a combination of C-H...O and C-H...π(arene) hydrogen bonds. The two independent molecules of compound (IV) form two different centrosymmetric dimers, one built from inversion-related pairs of C-H...O hydrogen bonds and the other from inversion-related pairs of C-H...π(arene) hydrogen bonds. Comparisons are made with related compounds.

Enantioselective synthesis of chiral 3-aryl-1-indanones through rhodium-catalyzed asymmetric intramolecular 1,4-addition.

PubMed

Yu, Yue-Na; Xu, Ming-Hua

2013-03-15

Enantioselective synthesis of potentially useful chiral 3-aryl-1-indanones was achieved through a rhodium-catalyzed asymmetric intramolecular 1,4-addition of pinacolborane chalcone derivatives using extraordinary simple MonoPhos as chiral ligand under relatively mild conditions. This novel protocol offers an easy access to a wide variety of enantioenriched 3-aryl-1-indanone derivatives in high yields (up to 95%) with excellent enantioselectivities (up to 95% ee).

Silencing CHALCONE SYNTHASE in Maize Impedes the Incorporation of Tricin into Lignin and Increases Lignin Content.

PubMed

Eloy, Nubia B; Voorend, Wannes; Lan, Wu; Saleme, Marina de Lyra Soriano; Cesarino, Igor; Vanholme, Ruben; Smith, Rebecca A; Goeminne, Geert; Pallidis, Andreas; Morreel, Kris; Nicomedes, José; Ralph, John; Boerjan, Wout

2017-02-01

Lignin is a phenolic heteropolymer that is deposited in secondary-thickened cell walls, where it provides mechanical strength. A recent structural characterization of cell walls from monocot species showed that the flavone tricin is part of the native lignin polymer, where it is hypothesized to initiate lignin chains. In this study, we investigated the consequences of altered tricin levels on lignin structure and cell wall recalcitrance by phenolic profiling, nuclear magnetic resonance, and saccharification assays of the naturally silenced maize (Zea mays) C2-Idf (inhibitor diffuse) mutant, defective in the CHALCONE SYNTHASE Colorless2 (C2) gene. We show that the C2-Idf mutant produces highly reduced levels of apigenin- and tricin-related flavonoids, resulting in a strongly reduced incorporation of tricin into the lignin polymer. Moreover, the lignin was enriched in β-β and β-5 units, lending support to the contention that tricin acts to initiate lignin chains and that, in the absence of tricin, more monolignol dimerization reactions occur. In addition, the C2-Idf mutation resulted in strikingly higher Klason lignin levels in the leaves. As a consequence, the leaves of C2-Idf mutants had significantly reduced saccharification efficiencies compared with those of control plants. These findings are instructive for lignin engineering strategies to improve biomass processing and biochemical production. © 2017 American Society of Plant Biologists. All Rights Reserved.

Silencing CHALCONE SYNTHASE in Maize Impedes the Incorporation of Tricin into Lignin and Increases Lignin Content

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eloy, Nubia B.; Voorend, Wannes; Lan, Wu

Lignin is a phenolic heteropolymer that is deposited in secondary-thickened cell walls, where it provides mechanical strength. A recent structural characterization of cell walls from monocot species showed that the flavone tricin is part of the native lignin polymer, where it is hypothesized to initiate lignin chains. In this study, we investigated the consequences of altered tricin levels on lignin structure and cell wall recalcitrance by phenolic profiling, nuclear magnetic resonance, and saccharification assays of the naturally silenced maize (Zea mays) C2-Idf (inhibitor diffuse) mutant, defective in the CHALCONE SYNTHASE Colorless2 (C2) gene. We show that the C2-Idf mutant producesmore » highly reduced levels of apigenin- and tricin-related flavonoids, resulting in a strongly reduced incorporation of tricin into the lignin polymer. Moreover, the lignin was enriched in β-β and β-5 units, lending support to the contention that tricin acts to initiate lignin chains and that, in the absence of tricin, more monolignol dimerization reactions occur. In addition, the C2-Idf mutation resulted in strikingly higher Klason lignin levels in the leaves. As a consequence, the leaves of C2-Idf mutants had significantly reduced saccharification efficiencies compared with those of control plants. These findings are instructive for lignin engineering strategies to improve biomass processing and biochemical production.« less

Silencing CHALCONE SYNTHASE in Maize Impedes the Incorporation of Tricin into Lignin and Increases Lignin Content1[OPEN

PubMed Central

2017-01-01

Lignin is a phenolic heteropolymer that is deposited in secondary-thickened cell walls, where it provides mechanical strength. A recent structural characterization of cell walls from monocot species showed that the flavone tricin is part of the native lignin polymer, where it is hypothesized to initiate lignin chains. In this study, we investigated the consequences of altered tricin levels on lignin structure and cell wall recalcitrance by phenolic profiling, nuclear magnetic resonance, and saccharification assays of the naturally silenced maize (Zea mays) C2-Idf (inhibitor diffuse) mutant, defective in the CHALCONE SYNTHASE Colorless2 (C2) gene. We show that the C2-Idf mutant produces highly reduced levels of apigenin- and tricin-related flavonoids, resulting in a strongly reduced incorporation of tricin into the lignin polymer. Moreover, the lignin was enriched in β-β and β-5 units, lending support to the contention that tricin acts to initiate lignin chains and that, in the absence of tricin, more monolignol dimerization reactions occur. In addition, the C2-Idf mutation resulted in strikingly higher Klason lignin levels in the leaves. As a consequence, the leaves of C2-Idf mutants had significantly reduced saccharification efficiencies compared with those of control plants. These findings are instructive for lignin engineering strategies to improve biomass processing and biochemical production. PMID:27940492

Analytical methods for quantitation of prenylated flavonoids from hops.

PubMed

Nikolić, Dejan; van Breemen, Richard B

2013-01-01

The female flowers of hops ( Humulus lupulus L.) are used as a flavoring agent in the brewing industry. There is growing interest in possible health benefits of hops, particularly as estrogenic and chemopreventive agents. Among the possible active constituents, most of the attention has focused on prenylated flavonoids, which can chemically be classified as prenylated chalcones and prenylated flavanones. Among chalcones, xanthohumol (XN) and desmethylxanthohumol (DMX) have been the most studied, while among flavanones, 8-prenylnaringenin (8-PN) and 6-prenylnaringenin (6-PN) have received the most attention. Because of the interest in medicinal properties of prenylated flavonoids, there is demand for accurate, reproducible and sensitive analytical methods to quantify these compounds in various matrices. Such methods are needed, for example, for quality control and standardization of hop extracts, measurement of the content of prenylated flavonoids in beer, and to determine pharmacokinetic properties of prenylated flavonoids in animals and humans. This review summarizes currently available analytical methods for quantitative analysis of the major prenylated flavonoids, with an emphasis on the LC-MS and LC-MS-MS methods and their recent applications to biomedical research on hops. This review covers all methods in which prenylated flavonoids have been measured, either as the primary analytes or as a part of a larger group of analytes. The review also discusses methodological issues relating to the quantitative analysis of these compounds regardless of the chosen analytical approach.

Tailoring tobacco hairy root metabolism for the production of stilbenes.

PubMed

Hidalgo, Diego; Georgiev, Milen; Marchev, Andrey; Bru-Martínez, Roque; Cusido, Rosa M; Corchete, Purificación; Palazon, Javier

2017-12-21

Tobacco hairy root (HR) cultures, which have been widely used for the heterologous production of target compounds, have an innate capacity to bioconvert exogenous t-resveratrol (t-R) into t-piceatannol (t-Pn) and t-pterostilbene (t-Pt). We established genetically engineered HR carrying the gene encoding stilbene synthase (STS) from Vitis vinifera and/or the transcription factor (TF) AtMYB12 from Arabidopsis thaliana, in order to generate a holistic response in the phenylpropanoid pathway and coordinate the up-regulation of multiple metabolic steps. Additionally, an artificial microRNA for chalcone synthase (amiRNA CHS) was utilized to arrest the normal flux through the endogenous chalcone synthase (CHS) enzyme, which would otherwise compete for precursors with the STS enzyme imported for the flux deviation. The transgenic HR were able to biosynthesize the target stilbenes, achieving a production of 40 μg L -1 of t-R, which was partially metabolized into t-Pn and t-Pt (up to 2.2 μg L -1 and 86.4 μg L -1 , respectively), as well as its glucoside piceid (up to 339.7 μg L -1 ). Major metabolic perturbations were caused by the TF AtMYB12, affecting both primary and secondary metabolism, which confirms the complexity of biotechnological systems based on seed plant in vitro cultures for the heterologous production of high-value molecules.

Analysis of the Expression of Anthocyanin Pathway Genes in Developing Vitis vinifera L. cv Shiraz Grape Berries and the Implications for Pathway Regulation.

PubMed Central

Boss, P. K.; Davies, C.; Robinson, S. P.

1996-01-01

Anthocyanin synthesis in Vitis vinifera L. cv Shiraz grape berries began 10 weeks postflowering and continued throughout berry ripening. Expression of seven genes of the anthocyanin biosynthetic pathway (phenylalanine ammonia lyase [PAL], chalcone synthase [CHS], chalcone isomerase [CHI], flavanone-3-hydroxylase [F3H], dihydroflavonol 4-reductase [DFR], leucoanthocyanidin dioxygen-ase [LDOX], and UDP glucose-flavonoid 3-o-glucosyl transferase [UFGT]) was determined. In flowers and grape berry skins, expression of all of the genes, except UFGT, was detected up to 4 weeks postflowering, followed by a reduction in this expression 6 to 8 weeks postflowering. Expression of CHS, CHI, F3H, DFR, LDOX, and UFGT then increased 10 weeks postflowering, coinciding with the onset of anthocyanin synthesis. In grape berry flesh, no PAL or UFGT expression was detected at any stage of development, but CHS, CHI, F3H, DFR, and LDOX were expressed up to 4 weeks postflowering. These results indicate that the onset of anthocyanin synthesis in ripening grape berry skins coincides with a coordinated increase in expression of a number of genes in the anthocyanin biosynthetic pathway, suggesting the involvement of regulatory genes. UFGT is regulated independently of the other genes, suggesting that in grapes the major control point in this pathway is later than that observed in maize, petunia, and snapdragon. PMID:12226348

Silencing CHALCONE SYNTHASE in Maize Impedes the Incorporation of Tricin into Lignin and Increases Lignin Content

DOE PAGES

Eloy, Nubia B.; Voorend, Wannes; Lan, Wu; ...

2016-12-09

Lignin is a phenolic heteropolymer that is deposited in secondary-thickened cell walls, where it provides mechanical strength. A recent structural characterization of cell walls from monocot species showed that the flavone tricin is part of the native lignin polymer, where it is hypothesized to initiate lignin chains. In this study, we investigated the consequences of altered tricin levels on lignin structure and cell wall recalcitrance by phenolic profiling, nuclear magnetic resonance, and saccharification assays of the naturally silenced maize (Zea mays) C2-Idf (inhibitor diffuse) mutant, defective in the CHALCONE SYNTHASE Colorless2 (C2) gene. We show that the C2-Idf mutant producesmore » highly reduced levels of apigenin- and tricin-related flavonoids, resulting in a strongly reduced incorporation of tricin into the lignin polymer. Moreover, the lignin was enriched in β-β and β-5 units, lending support to the contention that tricin acts to initiate lignin chains and that, in the absence of tricin, more monolignol dimerization reactions occur. In addition, the C2-Idf mutation resulted in strikingly higher Klason lignin levels in the leaves. As a consequence, the leaves of C2-Idf mutants had significantly reduced saccharification efficiencies compared with those of control plants. These findings are instructive for lignin engineering strategies to improve biomass processing and biochemical production.« less

An Antedrug of the CXCL12 Neutraligand Blocks Experimental Allergic Asthma without Systemic Effect in Mice*

PubMed Central

Daubeuf, François; Hachet-Haas, Muriel; Gizzi, Patrick; Gasparik, Vincent; Bonnet, Dominique; Utard, Valérie; Hibert, Marcel; Frossard, Nelly; Galzi, Jean-Luc

2013-01-01

The chemokine receptor CXCR4 and its chemokine CXCL12 are involved in normal tissue patterning but also in tumor cell growth and survival as well as in the recruitment of immune and inflammatory cells, as successfully demonstrated using agents that block either CXCL12 or CXCR4. In order to achieve selectivity in drug action on the CXCR4/CXCL12 pair, in particular in the airways, drugs should be delivered as selectively as possible in the treated tissue and should not diffuse in the systemic circulation, where it may reach undesired organs. To this end, we used a previously unexploited Knoevenagel reaction to create a short lived drug, or soft drug, based on the CXCL12-neutralizing small molecule, chalcone 4, which blocks binding of CXCL12 to CXCR4. We show that the compound, carbonitrile-chalcone 4, blocks the recruitment of eosinophils to the airways in ovalbumin-sensitized and challenged mice in vivo when administered directly to the airways by the intranasal route, but not when administered systemically by the intraperitoneal route. We show that the lack of effect at a distant site is due to the rapid degradation of the molecule to inactive fragments. This approach allows selective action of the CXCL12 neutraligands although the target protein is widely distributed in the organism. PMID:23449983

Licochalcone A, a novel antiparasitic agent with potent activity against human pathogenic protozoan species of Leishmania.

PubMed Central

Chen, M; Christensen, S B; Blom, J; Lemmich, E; Nadelmann, L; Fich, K; Theander, T G; Kharazmi, A

1993-01-01

Licochalcone A, an oxygenated chalcone isolated from the roots of Chinese licorice plant, inhibited the growth of both Leishmania major and Leishmania donovani promastigotes and amastigotes. The structure of the licochalcone A was established by mass and nuclear magnetic resonance spectroscopies and by synthesis, and its purity was verified by high-pressure liquid chromatography. The 50% inhibition of growth of logarithmic- and stationary-phase promastigotes of L. major, as measured by [3H]thymidine uptake, were 4 and 2.5 micrograms/ml, respectively. The growth of L. major promastigotes was totally inhibited after a 20-h incubation period with licochalcone A at 5 micrograms/ml. At a concentration of 0.5 microgram/ml, licochalcone A markedly reduced the infection rate of human peripheral blood monocyte-derived macrophages and U937 cells with L. major promastigotes and exhibited a strong intracellular killing of the parasite. These data show that intracellular Leishmania amastigotes are more susceptible than promastigotes to licochalcone A. Results of studies on the site of action of licochalcone A indicate that the target organelle appears to be the parasite mitochondria. These findings demonstrate that licochalcone A in concentrations that are nontoxic to host cells exhibits a strong antileishmanial activity and that appropriate substituted chalcones might be a new class of antileishmanial drugs. Images PMID:8109916

O2-Dependent Efficacy of Novel Piperidine- and Piperazine-Based Chalcones against the Human Parasite Giardia intestinalis

PubMed Central

Bahadur, Vijay; Mastronicola, Daniela; Tiwari, Hemandra Kumar; Kumar, Yogesh; Falabella, Micol; Pucillo, Leopoldo Paolo; Sarti, Paolo

2014-01-01

Giardia intestinalis is the most frequent protozoan agent of intestinal diseases worldwide. Though commonly regarded as an anaerobic pathogen, it preferentially colonizes the fairly oxygen-rich mucosa of the proximal small intestine. Therefore, when testing new potential antigiardial drugs, O2 should be taken into account, since it also reduces the efficacy of metronidazole, the gold standard drug against giardiasis. In this study, 46 novel chalcones were synthesized by microwave-assisted Claisen-Schmidt condensation, purified, characterized by high-resolution mass spectrometry, 1H and 13C nuclear magnetic resonance, and infrared spectroscopy, and tested for their toxicity against G. intestinalis under standard anaerobic conditions. As a novel approach, compounds showing antigiardial activity under anaerobiosis were also assayed under microaerobic conditions, and their selectivity against parasitic cells was assessed in a counterscreen on human epithelial colorectal adenocarcinoma cells. Among the tested compounds, three [30(a), 31(e), and 33] were more effective in the presence of O2 than under anaerobic conditions and killed the parasite 2 to 4 times more efficiently than metronidazole under anaerobiosis. Two of them [30(a) and 31(e)] proved to be selective against parasitic cells, thus representing potential candidates for the design of novel antigiardial drugs. This study highlights the importance of testing new potential antigiardial agents not only under anaerobic conditions but also at low, more physiological O2 concentrations. PMID:24217695

Cytotoxic chalcones from some Indonesian Cryptocarya

NASA Astrophysics Data System (ADS)

Kurniadewi, F.; Syah, Y. M.; Juliawaty, L. D.; Hakim, E. H.; Koyama, K.; Kinoshita, K.

2017-07-01

Malignant tumors are one of the main causes of death in the world. Until now the search for cytotoxic (antitumor) compounds from nature, particularly from plants, is being a continuation activities. One group of plants that produce potential cytotoxic compounds is the Cryptocarya, one of the large genera of the Lauraceae family. As a part of our chemical and cytotoxic evaluation of the Cryptocarya species, we examined three species of Indonesian Cryptocarya. The sample of the wood of C. konishii hayata was collected from Cibodas Botanical Garden, West Java while the stem bark of C. phoebeopsis and C. cagayanensis were obtained from Sorong, Papua. Our investigation of flavonoid constituents on these species afforded three chalcone compounds i.e. desmethylinfectocaryone (1), infectocaryone (2) and cryptocaryone (3). The molecular structures of the isolated compounds were determined based on spectroscopic data, including UV, IR, 1D and 2D NMR. Cytotoxic effects of the compounds were evaluated using MTT [3-(4,5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide] assay. Compound 1, 2 and 3 displayed strong cytotoxic properties (IC50 < 2 μg/mL) against Murine Leukemia P388 and HL 60 (blood premyelocytic leukemia) cells whereas 2 and 3 exhibited strong cytotoxicity properties against HCT116 (colon cancer). Cryptocaryone (3) also showed moderate cytotoxic properties (IC50 < 10 μg/mL) towards A549 (human lung adenocarcinoma epithelial) cells.

Likelihood analysis of the chalcone synthase genes suggests the role of positive selection in morning glories (Ipomoea).

PubMed

Yang, Ji; Gu, Hongya; Yang, Ziheng

2004-01-01

Chalcone synthase (CHS) is a key enzyme in the biosynthesis of flavonoides, which are important for the pigmentation of flowers and act as attractants to pollinators. Genes encoding CHS constitute a multigene family in which the copy number varies among plant species and functional divergence appears to have occurred repeatedly. In morning glories (Ipomoea), five functional CHS genes (A-E) have been described. Phylogenetic analysis of the Ipomoea CHS gene family revealed that CHS A, B, and C experienced accelerated rates of amino acid substitution relative to CHS D and E. To examine whether the CHS genes of the morning glories underwent adaptive evolution, maximum-likelihood models of codon substitution were used to analyze the functional sequences in the Ipomoea CHS gene family. These models used the nonsynonymous/synonymous rate ratio (omega = d(N)/ d(S)) as an indicator of selective pressure and allowed the ratio to vary among lineages or sites. Likelihood ratio test suggested significant variation in selection pressure among amino acid sites, with a small proportion of them detected to be under positive selection along the branches ancestral to CHS A, B, and C. Positive Darwinian selection appears to have promoted the divergence of subfamily ABC and subfamily DE and is at least partially responsible for a rate increase following gene duplication.

Chalcone synthase genes from milk thistle (Silybum marianum): isolation and expression analysis.

PubMed

Sanjari, Sepideh; Shobbar, Zahra Sadat; Ebrahimi, Mohsen; Hasanloo, Tahereh; Sadat-Noori, Seyed-Ahmad; Tirnaz, Soodeh

2015-12-01

Silymarin is a flavonoid compound derived from milk thistle (Silybum marianum) seeds which has several pharmacological applications. Chalcone synthase (CHS) is a key enzyme in the biosynthesis of flavonoids; thereby, the identification of CHS encoding genes in milk thistle plant can be of great importance. In the current research, fragments of CHS genes were amplified using degenerate primers based on the conserved parts of Asteraceae CHS genes, and then cloned and sequenced. Analysis of the resultant nucleotide and deduced amino acid sequences led to the identification of two different members of CHS gene family,SmCHS1 and SmCHS2. Third member, full-length cDNA (SmCHS3) was isolated by rapid amplification of cDNA ends (RACE), whose open reading frame contained 1239 bp including exon 1 (190 bp) and exon 2 (1049 bp), encoding 63 and 349 amino acids, respectively. In silico analysis of SmCHS3 sequence contains all the conserved CHS sites and shares high homology with CHS proteins from other plants.Real-time PCR analysis indicated that SmCHS1 and SmCHS3 had the highest transcript level in petals in the early flowering stage and in the stem of five upper leaves, followed by five upper leaves in the mid-flowering stage which are most probably involved in anthocyanin and silymarin biosynthesis.

Variation in Key Flavonoid Biosynthetic Enzymes and Phytochemicals in 'Rio Red' Grapefruit (Citrus paradisi Macf.) during Fruit Development.

PubMed

Chaudhary, Priyanka R; Bang, Haejeen; Jayaprakasha, Guddadarangavvanahally K; Patil, Bhimanagouda S

2016-11-30

In the current study, the phytochemical contents and expression of genes involved in flavonoid biosynthesis in Rio Red grapefruit were studied at different developmental and maturity stages for the first time. Grapefruit were harvested in June, August, November, January, and April and analyzed for the levels of carotenoids, vitamin C, limonoids, flavonoids, and furocoumarins by HPLC. In addition, genes encoding for phenylalanine ammonia-lyase (PAL), chalcone synthase (CHS), chalcone isomerase (CHI), and 1,2-rhamnosyltransferase (2RT) were isolated, and their expression in grapefruit juice vesicles was studied. Fruit maturity had significant influence on the expression of the genes, with PAL, CHS, and CHI having higher expression in immature fruits (June), whereas 2RT expression was higher in mature fruits (November and January). The levels of flavonoids (except naringin and poncirin), vitamin C, and furocoumarins gradually decreased from June to April. Furthermore, limonin levels sharply decreased in January. Lycopene decreased whereas β-carotene gradually increased with fruit maturity. Naringin did not exactly follow the pattern of 2RT or of PAL, CHS, and CHI expression, indicating that the four genes may have complementary effects on the level of naringin. Nevertheless, of the marketable fruit stages, early-season grapefruits harvested in November contained more beneficial phytochemicals as compared to mid- and late-season fruits harvested in January and April, respectively.

Crystal structures, in-silico study and anti-microbial potential of synthetic monocarbonyl curcuminoids

NASA Astrophysics Data System (ADS)

Ud Din, Zia; Serrano, N. F. G.; Ademi, Kastriot; Sousa, C. P.; Deflon, Victor Marcelo; Maia, Pedro Ivo da Silva; Rodrigues-Filho, Edson

2017-09-01

In this work the screening of 20 unsymmetrical chalcone and curcuminoids analogues in regard of their antimicrobial properties was conducted. Electron donating groups in the aromatic rings in the chalcone and curcuminoid derivatives produced higher antimicrobial effect. Compounds 1, 9 and 15 exhibited good activity against Escherichia coli and Staphylococcus aureus. These compounds were further evaluated against nine micro-organisms of pathological interest. Pharmmaper was used for target fishing of compounds against important bacterial targets. Molecular Docking helped to verify the results of these compounds against the selected bacterial target D-alanyl-D-alanine carboxypeptidase (PDB ID: 1PW1). The crystal structure of ligand and docked conformers in the active site of 1PW1 were analyzed. As a result structure-activity relationships are proposed. Structures of compounds 14 and 16 were obtained through single crystals X-ray diffraction studies. Compound 14 crystallizes in monoclinic space group P21/c with unit cell dimensions a = 13.1293(3) Å, b = 17.5364(4) Å, c = 15.1433(3) Å, β = 95.6440(10), V = 3469.70(13) Å3 and Z = 8. Compound 16 crystallizes in triclinic space group Pī with unit cell dimensions a = 6.8226(4) Å, b = 7.2256(4) Å, c = 18.1235(12) Å, β = 87.322(4), V = 850.57(9) Å3 and Z = 2.

An anti-inflammatory chalcone derivative prevents heart and kidney from hyperlipidemia-induced injuries by attenuating inflammation.

PubMed

Chen, Xiong; Yu, Weihui; Li, Weixin; Zhang, Hailing; Huang, Weijian; Wang, Jingying; Zhu, Weiwei; Fang, Qilu; Chen, Chao; Li, Xiaokun; Liang, Guang

2018-01-01

Obesity is a growing pandemic in both developed and developing countries. Lipid overload in obesity generates a chronic, low-grade inflammation state. Increased inflammation in heart and renal tissues has been shown to promote the progression of heart and renal damage in obesity. Previously, we found that a novel chalcone derivative, L6H21, inhibited lipopolysaccharide-induced inflammatory response. In the present study, we investigated the effects of L6H21 on inflammatory responses in culture and in animal models of lipid overload. We utilized palmitic acid (PA) challenging in mouse peritoneal macrophages and apolipoprotein E knockout (ApoE -/- ) mice fed a high fat diet (HFD) to study whether L6H21 mitigates the inflammatory response. Our studies show that L6H21 significantly reduced PA-induced expression of inflammatory cytokines in macrophages by inhibiting mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NFκB) signaling pathways. L6H21 also reduced fibrosis in the kidney and heart tissues, and indices of inflammatory response in the ApoE -/- mice fed a HFD. These effects in vivo were also associated with inhibition of MAPK and NFκB signaling by L6H21. These findings strongly suggest that L6H21 may be a potential agent for high fat diet-induced injuries in heart and kidney. Copyright © 2017. Published by Elsevier Inc.

Increased chalcone synthase (CHS) expression is associated with dicamba resistance in Kochia scoparia.

PubMed

Pettinga, Dean J; Ou, Junjun; Patterson, Eric L; Jugulam, Mithila; Westra, Philip; Gaines, Todd A

2017-10-30

Resistance to the synthetic auxin herbicide dicamba is increasingly problematic in Kochia scoparia. The resistance mechanism in an inbred dicamba-resistant K. scoparia line (9425R) was investigated using physiological and transcriptomics (RNA-Seq) approaches. No differences were found in dicamba absorption or metabolism between 9425R and a dicamba-susceptible line, but 9425R was found to have significantly reduced dicamba translocation. Known auxin-responsive genes ACC synthase (ACS) and indole-3-acetic acid amino synthetase (GH3) were transcriptionally induced following dicamba treatment in dicamba-susceptible K. scoparia but not in 9425R. Chalcone synthase (CHS), the gene regulating synthesis of the flavonols quertecin and kaemperfol, was found to have twofold higher transcription in 9425R both without and 12 h after dicamba treatment. Increased CHS transcription co-segregated with dicamba resistance in a forward genetics screen using an F 2 population. Prior work has shown that the flavonols quertecin and kaemperfol compete with auxin for intercellular movement and vascular loading via ATP-binding cassette subfamily B (ABCB) membrane transporters. The results of this study support a model in which constitutively increased CHS expression in the meristem produces more flavonols that would compete with dicamba for intercellular transport by ABCB transporters, resulting in reduced dicamba translocation. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Synthesis and Crystal Structure of a Chalcone Derivative

NASA Astrophysics Data System (ADS)

Singh, Vikram D.; Salian, Vinutha V.; Narayana, B.; Sarojini, B. K.; Kamni; Anthal, Sumati; Kant, Rajni

2017-12-01

(2E)-3-(anthrance-9-yl)-1-(3,4-dichlorophenyl)prop-2-en-1-one [C23H14OCl2] is synthesized and its crystal structure is determined by single X-ray diffraction. There exist two molecules in the asymmetric unit. The dihedral angle between the benzene and anthracene moiety of the molecule A and B is 86.51(12)° and 76.42(13)°, respectively. No classical hydrogen bonds are observed and only van der Waals forces stabilize the crystal packing.

Trypanocidal activity of a new pterocarpan and other secondary metabolites of plants from Northeastern Brazil flora.

PubMed

Vieira, Nashira Campos; Espíndola, Laila Salmen; Santana, Jaime Martins; Veras, Maria Leopoldina; Pessoa, Otília Deusdênia Loiola; Pinheiro, Sávio Moita; de Araújo, Renata Mendonça; Lima, Mary Anne Sousa; Silveira, Edilberto Rocha

2008-02-15

Two hundred fifteen compounds isolated from plants of Northeastern Brazil flora have been assayed against epimastigote forms of Trypanosoma cruzi, using the tetrazolium salt MTT as an alternative method. Eight compounds belonging to four different species: Harpalyce brasiliana (Fabaceae), Acnistus arborescens and Physalis angulata (Solanaceae), and Cordia globosa (Boraginaceae) showed significant activity. Among them, a novel and a known pterocarpan, a chalcone, four withasteroids, and a meroterpene benzoquinone were the represented chemical classes.

Synthesis and cytotoxicity of 2,5-dihydroxychalcones and related compounds.

PubMed

Nam, Nguyen-Hai; Hong, Dong-Ho; You, Young-Jae; Kim, Yong; Bang, Seong-Cheol; Kim, Hwan-Mook; Ahn, Byung-Zun

2004-06-01

A series of 2, 5-dihydroxychalcones and related compounds were synthesized, and their cytotoxicities against tumor cell lines and human umbilical venous endothelial cells (HUVEC) evaluated. It was found that chalcones, with electron-withdrawing substituents on an A ring, exhibited significant cytotoxicities. Among the synthesized compounds, 2'-chloro-2, 5-dihydroxychalcone (9) was most potent, with an IC50 value as low as 0.31 microg/mL. This compound also exhibited a significant cytotoxic selectivity toward HUVEC.

Molecular Diversity by Olefin Cross-Metathesis on Solid Support. Generation of Libraries of Biologically Promising β-Lactam Derivatives.

PubMed

Méndez, Luciana; Poeylaut-Palena, Andrés A; Mata, Ernesto G

2018-05-16

The application of the reagent-based diversification strategy for generation of libraries of biologically promising β-lactam derivatives is described. Key features are the versatility of the linker used and the cross-metathesis functionalization at the cleavage step. From an immobilized primary library, diversity was expanded by applying different cleavage conditions, leading to a series of cholesterol absorption inhibitor analogues together with interesting hybrid compounds through incorporation of a chalcone moiety.

Design and environmentally benign synthesis of novel thiophene appended pyrazole analogues as anti-inflammatory and radical scavenging agents: Crystallographic, in silico modeling, docking and SAR characterization.

PubMed

Prabhudeva, Malledevarapura Gurumurthy; Bharath, Srinivasan; Kumar, Achutha Dileep; Naveen, Shivalingegowda; Lokanath, Neratur Krishnappagowda; Mylarappa, Bantaganahalli Ningappa; Kumar, Kariyappa Ajay

2017-08-01

Oxidative-stress induces inflammatory diseases and infections caused by drug-resistant microbial strains are on the rise necessitating the discovery of novel small-molecules for intervention therapy. The current study presents an effective and new green protocol for the synthesis of thiophene-appended pyrazoles through 3+2 annulations method. Chalcones 3(a-g) were prepared from 5-chloro-2-acetylthiophene and aromatic aldehydes by Claisen-Schmidt approach. The reaction of chalcones 3(a-g) with phenylhydrazine hydrochlorides 4(a-b) in acetic acid (30%) medium and also with freshly prepared citrus extract medium under reflux conditions produced the thiophene appended pyrazoles 5(a-l) in moderate yields. Structures of synthesized new pyrazoles were confirmed by spectral studies, elemental analysis and single crystal X-ray diffraction studies. Further, preliminary assessment of the anti-inflammatory properties of the compounds showed that, amongst the series, compounds 5d, 5e and 5l have excellent anti-inflammatory activities. Further, compounds 5c, 5d, 5g, and 5i exhibited excellent DPPH radical scavenging abilities in comparison with the standard ascorbic acid. Furthermore, using detailed structural modeling and docking efforts, combined with preliminary SAR, we show possible structural and chemical features on both the small-molecules and the protein that might contribute to the binding and inhibition. Copyright © 2017 Elsevier Inc. All rights reserved.

Elevated gene expression in chalcone synthase enzyme suggests an increased production of flavonoids in skin and synchronized red cell cultures of North American native grape berries.

PubMed

Davis, Gina; Ananga, Anthony; Krastanova, Stoyanka; Sutton, Safira; Ochieng, Joel W; Leong, Stephen; Tsolova, Violetka

2012-06-01

Anthocyanins are antioxidants and are among the natural products synthesized via the flavonoid biosynthesis pathway. Anthocyanins have been recommended for dietary intake in the prevention of cardiovascular diseases, cancer, and age-related conditions such as Alzheimer's disease or dementia. With an increasingly aging population in many parts of the world, strategies for the commercial production of in vitro synchronized red cell cultures as natural antioxidants will be a significant contribution to human medicine. Red pigmented fruits such as grapes (Vitis sp.) are a major source of bioavailable anthocyanins and other polyphenols. Since the level of antioxidants varies among cultivars, this study is the first one that phytochemically and genetically characterizes native grape cultivars of North America to determine the optimal cultivar and berry cells for the production of anthocyanins as antioxidants. Using real-time PCR and bioinformatics approaches, we tested for the transcript expression of the chalcone synthase (CHS) gene, an enzyme involved in the flavonoid and anthocyanin biosynthesis pathway, in different parts of physiologically mature grape berries and in vitro synchronized red cells. A low level of expression was recorded in berry flesh, compared with an elevated expression in berry skins and in vitro synchronized red cells, suggesting increased production of flavonoids in skin and cell cultures. This preliminary study demonstrates the potential of functional genomics in natural products research as well as in systematic studies of North American native grapes, specifically in muscadine (Vitis rotundifolia).

PpASCL, the Physcomitrella patens Anther-Specific Chalcone Synthase-Like Enzyme Implicated in Sporopollenin Biosynthesis, Is Needed for Integrity of the Moss Spore Wall and Spore Viability

PubMed Central

Daku, Rhys M.; Rabbi, Fazle; Buttigieg, Josef; Coulson, Ian M.; Horne, Derrick; Martens, Garnet; Ashton, Neil W.; Suh, Dae-Yeon

2016-01-01

Sporopollenin is the main constituent of the exine layer of spore and pollen walls. The anther-specific chalcone synthase-like (ASCL) enzyme of Physcomitrella patens, PpASCL, has previously been implicated in the biosynthesis of sporopollenin, the main constituent of exine and perine, the two outermost layers of the moss spore cell wall. We made targeted knockouts of the corresponding gene, PpASCL, and phenotypically characterized ascl sporophytes and spores at different developmental stages. Ascl plants developed normally until late in sporophytic development, when the spores produced were structurally aberrant and inviable. The development of the ascl spore cell wall appeared to be arrested early in microspore development, resulting in small, collapsed spores with altered surface morphology. The typical stratification of the spore cell wall was absent with only an abnormal perine recognisable above an amorphous layer possibly representing remnants of compromised intine and/or exine. Equivalent resistance of the spore walls of ascl mutants and the control strain to acetolysis suggests the presence of chemically inert, defective sporopollenin in the mutants. Anatomical abnormalities of late-stage ascl sporophytes include a persistent large columella and an air space incompletely filled with spores. Our results indicate that the evolutionarily conserved PpASCL gene is needed for proper construction of the spore wall and for normal maturation and viability of moss spores. PMID:26752629

Molecular and Biochemical Analysis of Chalcone Synthase from Freesia hybrid in Flavonoid Biosynthetic Pathway

PubMed Central

Sun, Wei; Meng, Xiangyu; Liang, Lingjie; Jiang, Wangshu; Huang, Yafei; He, Jing; Hu, Haiyan; Almqvist, Jonas; Gao, Xiang; Wang, Li

2015-01-01

Chalcone synthase (CHS) catalyzes the first committed step in the flavonoid biosynthetic pathway. In this study, the cDNA (FhCHS1) encoding CHS from Freesia hybrida was successfully isolated and analyzed. Multiple sequence alignments showed that both the conserved CHS active site residues and CHS signature sequence were found in the deduced amino acid sequence of FhCHS1. Meanwhile, crystallographic analysis revealed that protein structure of FhCHS1 is highly similar to that of alfalfa CHS2, and the biochemical analysis results indicated that it has an enzymatic role in naringenin biosynthesis. Moreover, quantitative real-time PCR was performed to detect the transcript levels of FhCHS1 in flowers and different tissues, and patterns of FhCHS1 expression in flowers showed significant correlation to the accumulation patterns of anthocyanin during flower development. To further characterize the functionality of FhCHS1, its ectopic expression in Arabidopsis thaliana tt4 mutants and Petunia hybrida was performed. The results showed that overexpression of FhCHS1 in tt4 mutants fully restored the pigmentation phenotype of the seed coats, cotyledons and hypocotyls, while transgenic petunia expressing FhCHS1 showed flower color alteration from white to pink. In summary, these results suggest that FhCHS1 plays an essential role in the biosynthesis of flavonoid in Freesia hybrida and may be used to modify the components of flavonoids in other plants. PMID:25742495

Molecular and Biochemical Analysis of Chalcone Synthase from Freesia hybrid in flavonoid biosynthetic pathway.

PubMed

Sun, Wei; Meng, Xiangyu; Liang, Lingjie; Jiang, Wangshu; Huang, Yafei; He, Jing; Hu, Haiyan; Almqvist, Jonas; Gao, Xiang; Wang, Li

2015-01-01

Chalcone synthase (CHS) catalyzes the first committed step in the flavonoid biosynthetic pathway. In this study, the cDNA (FhCHS1) encoding CHS from Freesia hybrida was successfully isolated and analyzed. Multiple sequence alignments showed that both the conserved CHS active site residues and CHS signature sequence were found in the deduced amino acid sequence of FhCHS1. Meanwhile, crystallographic analysis revealed that protein structure of FhCHS1 is highly similar to that of alfalfa CHS2, and the biochemical analysis results indicated that it has an enzymatic role in naringenin biosynthesis. Moreover, quantitative real-time PCR was performed to detect the transcript levels of FhCHS1 in flowers and different tissues, and patterns of FhCHS1 expression in flowers showed significant correlation to the accumulation patterns of anthocyanin during flower development. To further characterize the functionality of FhCHS1, its ectopic expression in Arabidopsis thaliana tt4 mutants and Petunia hybrida was performed. The results showed that overexpression of FhCHS1 in tt4 mutants fully restored the pigmentation phenotype of the seed coats, cotyledons and hypocotyls, while transgenic petunia expressing FhCHS1 showed flower color alteration from white to pink. In summary, these results suggest that FhCHS1 plays an essential role in the biosynthesis of flavonoid in Freesia hybrida and may be used to modify the components of flavonoids in other plants.

Synergistic anticancer effect of cisplatin and Chal-24 combination through IAP and c-FLIPL degradation, Ripoptosome formation and autophagy-mediated apoptosis

PubMed Central

Shi, Shaoqing; Wang, Qiong; Xu, Jennings; Jang, Jun-Ho; Padilla, Mabel T.; Nyunoya, Toru; Xing, Chengguo; Zhang, Lin; Lin, Yong

2015-01-01

Drug resistance is a major hurdle in anticancer chemotherapy. Combined therapy using drugs with distinct mechanisms of function may increase anticancer efficacy. We have recently identified the novel chalcone derivative, chalcone-24 (Chal-24), as a potential therapeutic that kills cancer cells through activation of an autophagy-mediated necroptosis pathway. In this report, we investigated if Chal-24 can be combined with the frontline genotoxic anticancer drug, cisplatin for cancer therapy. The combination of Chal-24 and cisplatin synergistically induced apoptotic cytotoxicity in lung cancer cell lines, which was dependent on Chal-24-induced autophagy. While cisplatin slightly potentiated the JNK/Bcl2/Beclin1 pathway for autophagy activation, its combination with Chal-24 strongly triggered proteasomal degradation of the cellular inhibitor of apoptosis proteins (c-IAPs) and formation of the Ripoptosome complex that contains RIP1, FADD and caspase 8. Furthermore, the cisplatin and Chal-24 combination induced dramatic degradation of cellular FLICE (FADD-like IL-1β-converting enzyme)-inhibitory protein large (cFLIPL) which suppresses Ripoptosome-mediated apoptosis activation. These results establish a novel mechanism for potentiation of anticancer activity with the combination of Chal-24 and cisplatin: to enhance apoptosis signaling through Ripoptosome formation and to release the apoptosis brake through c-FLIPL degradation. Altogether, our work suggests that the combination of Chal-24 and cisplatin could be employed to improve chemotherapy efficacy. PMID:25682199

Chalcones in bioactive Argentine propolis collected in arid environments.

PubMed

Solórzano, Eliana; Vera, Nancy; Cuello, Soledad; Ordoñez, Roxana; Zampini, Catiana; Maldonado, Luis; Bedascarrasbure, Enrique; Isla, María I

2012-07-01

The aim of this study was to assess the chemical and biological profile of propolis samples collected in arid environments of north-western Argentina. The samples were from two phytogeographical regions (Prepuna and Monte de Catamarca Province). Propolis ethanolic extracts (PEE) and chloroform (CHL), hexane (HEX) and aqueous (AQ) sub-extracts of samples from three regions (CAT-I; CAT-II and CAT-III) were obtained. All PEE exhibited antioxidant activity in the DPPH radical scavenging assay (SC50 values between 28 and 43 microg DW/mL). The CHL extract was the most active (SC50 values between 10 and 37 microg DW/mL). The antioxidant activity in the beta-carotene bleaching assays was more effective for PEE and CHL (IC50 values between 2 and 9 microg DW/mL, respectively). A similar pattern was observed for antibacterial activity. The highest inhibitory effect on the growth of human Gram-positive bacteria was observed for CHL-III and CHL-I (Monte region) with minimal inhibitory concentration values (MIC100) of 50 to 100 microg DW/mL. Nine compounds were identified by HPLC-PAD. Two of them (2', 4'- dihydroxychalcone and 2',4'- dihydroxy 3'-methoxychalcone) were found only in propolis samples from the Monte phytogeographical region. We consider that the Argentine arid region is appropriate to place hives in order to obtain propolis of excellent quality because the dominant life forms in that environment are shrubby species that produce resinous exudates with a high content of chalcones, flavones and flavonols.

Absence of genotoxic effects of the chalcone (E)-1-(2-hydroxyphenyl)-3-(4-methylphenyl)-prop-2-en-1-one) and its potential chemoprevention against DNA damage using in vitro and in vivo assays

PubMed Central

2017-01-01

The chalcone (E)-1-(2-hydroxyphenyl)-3-(4-methylphenyl)-prop-2-en-1-one), or 2HMC, displays antileishmanial, antimalarial, and antioxidant activities. The aim of this study was to investigate the cytotoxic, genotoxic, mutagenic, and protective effects of 2HMC using the Ames mutagenicity test, the mouse bone marrow micronucleus test, and the comet assay in mice. In the assessment using the Ames test, 2HMC did not increase the number of His+ revertants in Salmonella typhimurium strains, demonstrating lack of mutagenicity. 2HMC showed no significant increase in micronucleated polychromatic erythrocyte frequency (MNPCE) in the micronucleus test, or in DNA strand breaks using the comet assay, evidencing absence of genotoxicity. Regarding cytotoxicity, 2HMC exhibited moderate cytotoxicity in mouse bone marrow cells by micronucleus test. 2HMC showed antimutagenic action in co-administration with the positive controls, sodium azide (SA) and 4-nitroquinoline-1-oxide (4NQO), in the Ames test. Co-administered and mainly pre-administered with cyclophosphamide (CPA), 2HMC caused a decrease in the frequency of MNPCE using the micronucleus test and in DNA strand breaks using the comet assay. Thus, 2HMC exhibited antimutagenic and antigenotoxic effects, displaying a DNA-protective effect against CPA, SA, and 4NQO carcinogens. In conclusion, 2HMC presented antimutagenic, antigenotoxic and moderate cytotoxic effects; therefore it is a promising molecule for cancer prevention. PMID:28207781

Absence of genotoxic effects of the chalcone (E)-1-(2-hydroxyphenyl)-3-(4-methylphenyl)-prop-2-en-1-one) and its potential chemoprevention against DNA damage using in vitro and in vivo assays.

PubMed

Lima, Débora Cristina da Silva; Vale, Camila Regina do; Véras, Jefferson Hollanda; Bernardes, Aline; Pérez, Caridad Noda; Chen-Chen, Lee

2017-01-01

The chalcone (E)-1-(2-hydroxyphenyl)-3-(4-methylphenyl)-prop-2-en-1-one), or 2HMC, displays antileishmanial, antimalarial, and antioxidant activities. The aim of this study was to investigate the cytotoxic, genotoxic, mutagenic, and protective effects of 2HMC using the Ames mutagenicity test, the mouse bone marrow micronucleus test, and the comet assay in mice. In the assessment using the Ames test, 2HMC did not increase the number of His+ revertants in Salmonella typhimurium strains, demonstrating lack of mutagenicity. 2HMC showed no significant increase in micronucleated polychromatic erythrocyte frequency (MNPCE) in the micronucleus test, or in DNA strand breaks using the comet assay, evidencing absence of genotoxicity. Regarding cytotoxicity, 2HMC exhibited moderate cytotoxicity in mouse bone marrow cells by micronucleus test. 2HMC showed antimutagenic action in co-administration with the positive controls, sodium azide (SA) and 4-nitroquinoline-1-oxide (4NQO), in the Ames test. Co-administered and mainly pre-administered with cyclophosphamide (CPA), 2HMC caused a decrease in the frequency of MNPCE using the micronucleus test and in DNA strand breaks using the comet assay. Thus, 2HMC exhibited antimutagenic and antigenotoxic effects, displaying a DNA-protective effect against CPA, SA, and 4NQO carcinogens. In conclusion, 2HMC presented antimutagenic, antigenotoxic and moderate cytotoxic effects; therefore it is a promising molecule for cancer prevention.

Synthesis, antihyperglycemic activity and computational studies of antioxidant chalcones and flavanones derived from 2,5 dihydroxyacetophenone

NASA Astrophysics Data System (ADS)

Tajammal, Affifa; Batool, Majda; Ramzan, Ayesha; Samra, Malka M.; Mahnoor, Idrees; Verpoort, Francis; Irfan, Ahmad; Al-Sehemi, Abdullah G.; Munawar, Munawar Ali; Basra, Muhammad Asim R.

2017-11-01

Chronic exposure of supraphysiologic glucose concentration to cells and tissues resulted in glucose toxicity which causes oxidative stress. Antioxidants have promising effect in suppressing the oxidative stress in the pathogenesis of diabetes mellitus (DM). Condensation of 2,5-dihydroxyacetophenone with different nitrobenzaldehydes was used to synthesize antioxidant nitro substituted chalcones along with nitro substituted flavanones in one step protocol. The compounds were characterized by IR, 1H NMR and 13C NMR and then screened for their in vitro antioxidant and in vivo antihyperglycemic activities. Postulated structures of the synthesized compounds were in agreement with their spectral data. The results indicated that the novel compound (2E)-1-(2,5-Dihydroxyphenyl)-3-(2-nitrophenyl) prop-2-en-1-one (2a) was potent antioxidant because of its lower IC50 value compared with trolox and ascorbic acid. Compound 2a also exhibited excellent antihyperglycemic activity in diabetic rats while the compound (E)-1-(2,5-Dihydroxyphenyl)-3-(4-nitrophenyl)prop-2-one (2c) suppressed the hyperglycemia more effectively in normal rats. The radical scavenging activity behavior was elucidated on the basis of hydrogen atom transfer and one-electron transfer mechanisms by density functional theory (DFT). The compound 2a showed the smallest ionization potential and bond dissociation enthalpy. Experimental and computational investigations concluded that compound 2a might be an effective antihyperglycemic agent because of its antioxidative nature and smallest ionization potential.

UV light selectively coinduces supply pathways from primary metabolism and flavonoid secondary product formation in parsley

PubMed Central

Logemann, Elke; Tavernaro, Annette; Schulz, Wolfgang; Somssich, Imre E.; Hahlbrock, Klaus

2000-01-01

The UV light-induced synthesis of UV-protective flavonoids diverts substantial amounts of substrates from primary metabolism into secondary product formation and thus causes major perturbations of the cellular homeostasis. Results from this study show that the mRNAs encoding representative enzymes from various supply pathways are coinduced in UV-irradiated parsley cells (Petroselinum crispum) with two mRNAs of flavonoid glycoside biosynthesis, encoding phenylalanine ammonia-lyase and chalcone synthase. Strong induction was observed for mRNAs encoding glucose 6-phosphate dehydrogenase (carbohydrate metabolism, providing substrates for the shikimate pathway), 3-deoxyarabinoheptulosonate 7-phosphate synthase (shikimate pathway, yielding phenylalanine), and acyl-CoA oxidase (fatty acid degradation, yielding acetyl-CoA), and moderate induction for an mRNA encoding S-adenosyl-homocysteine hydrolase (activated methyl cycle, yielding S-adenosyl-methionine for B-ring methylation). Ten arbitrarily selected mRNAs representing various unrelated metabolic activities remained unaffected. Comparative analysis of acyl-CoA oxidase and chalcone synthase with respect to mRNA expression modes and gene promoter structure and function revealed close similarities. These results indicate a fine-tuned regulatory network integrating those functionally related pathways of primary and secondary metabolism that are specifically required for protective adaptation to UV irradiation. Although the response of parsley cells to UV light is considerably broader than previously assumed, it contrasts greatly with the extensive metabolic reprogramming observed previously in elicitor-treated or fungus-infected cells. PMID:10677554

Synthesis, docking and ADMET studies of novel chalcone triazoles for anti-cancer and anti-diabetic activity.

PubMed

Chinthala, Yakaiah; Thakur, Sneha; Tirunagari, Shalini; Chinde, Srinivas; Domatti, Anand Kumar; Arigari, Niranjana Kumar; K V N S, Srinivas; Alam, Sarfaraz; Jonnala, Kotesh Kumar; Khan, Feroz; Tiwari, Ashok; Grover, Paramjit

2015-03-26

A series of novel chalcone-triazole derivatives were synthesized and screened for in vitro anticancer activity on the human cancer cell lines IMR32 (neuroblastoma), HepG2 (hepatoma) and MCF-7 (breast adenocarcinoma), DU-145 (prostate carcinoma), and A549 (lung adenocarcinoma). Among the tested compounds, 4r showed the most promising anticancer activity in all the cell lines whereas, compounds 4c (IC50 65.86 μM), 4e (IC50 66.28 μM), 4o (IC50 35.81 μM), 4q (IC50 50.82 μM) and 4s (IC50 48.63 μM) showed better activity than the standard doxorubicin (IC50 69.33 μM) in A549 cell line alone. Rat intestinal α-glucosidase inhibitory activity of the synthesized derivatives showed 4m (IC50 67.77 μM), 4p (IC50 74.94 in μM) and 4s (IC50 102.10 μM) as most active compared to others. The in silico docking of synthesized derivatives 4a-4t with DNA topoisomerase IIα revealed the LibDock score in the range of 71.2623-118.29 whereas, compounds 4h, 4m, 4p and 4s with docking target α-glucosidase were in the range of 100.372-107.784. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Plant defense genes are regulated by ethylene

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ecker, J.R.; Davis, R.W.

One of the earliest detectable events during plant-pathogen interaction is a rapid increase in ethylene biosynthesis. This gaseous plant stress hormone may be a signal for plants to activate defense mechanisms against invading pathogens such as bacteria, fungi, and viruses. The effect of ethylene on four plant genes involved in three separate plant defense response pathways was examined; these included (i and ii) genes that encode L-phenylalanine ammonia-lyase (EC 4.3.1.5) and 4-coumarate:CoA ligase (4-coumarate:CoA ligase (AMP-forming), EC 6.2.1.12), enzymes of the phenylpropanoid pathway, (iii) the gene encoding chalcone synthase, an enzyme of the flavonoid glycoside pathway, and (iv) the genesmore » encoding hydroxyproline-rich glycoprotein, a major protein component(s) of plant cell walls. Blot hybridization analysis of mRNA from ethylene-treated carrot roots reveals marked increases in the levels of phenylalanine ammonia-lyase mRNA, 4-coumarate CoA ligase mRNA, chalcone synthase mRNA, and certain hydroxyproline-rich glycoprotein transcripts. The effect of ethylene on hydroxyproline-rich glycoprotein mRNA accumulation was different from that of wounding. Ethylene induces two hydroxyproline-rich glycoprotein mRNAs (1.8 and 4.0 kilobases), whereas wounding of carrot root leads to accumulation of an additional hydroxyproline-rich mRNA (1.5 kilobases). These results indicate that at least two distinct signals, ethylene and a wound signal, can affect the expression of plant defense-response genes.« less

Silybin content and overexpression of chalcone synthase genes in Silybum marianum L. plants under abiotic elicitation.

PubMed

El-Garhy, Hoda A S; Khattab, Salah; Moustafa, Mahmoud M A; Abou Ali, Rania; Abdel Azeiz, Ahmed Z; Elhalwagi, Abeer; El Sherif, Fadia

2016-11-01

Silymarin, a Silybum marianum seed extract containing a mixture of flavonolignans including silybin, is being used as an antihepatotoxic therapy for liver diseases. In this study, the enhancing effect of gamma irradiation on plant growth parameters of S. marianum under salt stress was investigated. The effect of gamma irradiation, either as a single elicitor or coupled with salinity, on chalcone synthase (CHS) gene expression and silybin A + B yield was also evaluated. The silybin A + B content in S. marianum fruits was estimated by liquid chromatography-mass spectrometry (LC-MS/MS). An increase in silybin content was accompanied by up-regulation of the CHS1, CHS2 and CHS3 genes, which are involved in the silybin biosynthetic pathway. The highest silybin A + B production (0.77 g/100 g plant DW) and transcript levels of the three studied genes (100.2-, 91.9-, and 24.3-fold increase, respectively) were obtained with 100GY gamma irradiation and 4000 ppm salty water. The CHS2 and CHS3 genes were partially sequenced and submitted to the NCBI database under the accession numbers KT252908.1 and KT252909.1, respectively. Developing new approaches to stimulate silybin biosynthetic pathways could be a useful tool to potentiate the use of plants as renewable resources of medicinal compounds. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

The effects of metyrapone, chalcone epoxide, benzil, clotrimazole and related compounds on the activity of microsomal epoxide hydrolase in situ, in purified form and in reconstituted systems towards different substrates.

PubMed

Seidegård, J; DePierre, J W; Guenthner, T M; Oesch, F

1986-09-01

The influence of metyrapone, chalcone epoxide, benzil and clotrimazole on the activity of microsomal epoxide hydrolase towards styrene oxide, benzo[a]pyrene 4,5-oxide, estroxide and androstene oxide was investigated. The studies were performed using liver microsomes from rats, rabbits, mice and humans; epoxide hydrolase purified from rat liver microsomes to apparent homogeneity; and the purified enzyme incorporated into liposomes composed of egg-yolk phosphatidylcholine or total rat liver microsomal lipids. All four effectors were found to activate the hydrolysis of styrene oxide by epoxide hydrolase in situ in rat liver microsomal membranes, in agreement with earlier findings. Epoxide hydrolase activity towards styrene oxide in liver microsomes from mouse, rabbit and man was also increased by all four effectors. The most striking effect was a 680% activation by clotrimazole in rat liver microsomes. However, none of the effectors activated microsomal epoxide hydrolase more than 50% when benzo[a]pyrene 4,5-oxide, estroxide or androstene oxide was used as substrate. Indeed, clotrimazole was found to inhibit microsomal epoxide hydrolase activity towards estroxide 30-50% and towards androstene oxide 60-90%. The effects of these four compounds were found to be virtually identical in the preparations from rats, rabbits, mice and humans. The effects of metyrapone, chalcone epoxide, benzil and clotrimazole on purified epoxide hydrolase were qualitatively the same as those on epoxide hydrolase in intact microsomes, but much smaller in magnitude. These effects were increased in magnitude only slightly by incorporation of the purified enzyme into liposomes made from egg-yolk phosphatidylcholine. However, when incorporation into liposomes composed of total microsomal lipids was performed, the effects seen were essentially of the same magnitude as with intact microsomes. When the extent of activation was plotted against effector concentration, three different patterns were found with different effectors. Activation of epoxide hydrolase activity towards styrene oxide by clotrimazole was found to be uncompetitive with the substrate and highly structure specific. On the other hand, inhibition of epoxide hydrolase activity towards androstene oxide by clotrimazole was found to be competitive in microsomes. It is concluded that the marked effects of these four modulators on microsomal epoxide hydrolase activity are due to an interaction with the enzyme protein itself, but that the presence of total microsomal phospholipids allows the maximal expression leading to similar degrees of modulation as those observed in intact microsomes.(ABSTRACT TRUNCATED AT 400 WORDS)

One-pot synthesis of pyrrole-2-carboxylates and -carboxamides via an electrocyclization/oxidation sequence.

PubMed

Imbri, Dennis; Netz, Natalie; Kucukdisli, Murat; Kammer, Lisa Marie; Jung, Philipp; Kretzschmann, Annika; Opatz, Till

2014-12-05

An electrocyclic ring closure is the key step of an efficient one-pot method for the synthesis of pyrrole-2-carboxylates and -carboxamides from chalcones and glycine esters or amides. The 3,4-dihydro-2H-pyrrole intermediates generated in situ are oxidized to the corresponding pyrroles by stoichiometric oxidants or by catalytic copper(II) and air in moderate to high yields. A wide range of functional groups are tolerated, and further combination with an in situ bromination gives access to polyfunctional pyrrole scaffolds.

Synthesis, crystal structure and redox properties of dihydropyrazole-bridged ferrocene-based derivatives

NASA Astrophysics Data System (ADS)

Li, Heng-Dong; Ma, Zai-He; Yang, Kun; Xie, Li-Li; Yuan, Yao-Feng

2012-09-01

Dihydropyrazole-bridged ferrocene-based derivatives were prepared by corresponding chalcones with hydrazine hydrate, then acylation with 3-(ethoxycarbonyl)propionyl chloride directly in high yields and purity. All of these compounds were characterized by MS, IR, 1H NMR, 13C NMR and elemental analysis. The relationship between the structure and redox properties was investigated based on the results of single crystal X-ray structure determinations and cyclic voltammetry. The mechanism of the electron transfer for representative compound 4b was verified by density functional theory (DFT) calculations.

Tyrosinase inhibitors from the wood of Artocarpus heterophyllus.

PubMed

Nguyen, Nhan Trung; Nguyen, Mai Ha Khoa; Nguyen, Hai Xuan; Bui, Ngan Kim Nguyen; Nguyen, Mai Thanh Thi

2012-11-26

From the methanolic-soluble extract of the wood of Artocarpus heterophyllus, four new flavones, artocarmins A-D (1-4), and three new chalcones, artocarmitins A-C (5-7), have been isolated together with 13 known compounds. Their structures were determined on the basis of the spectroscopic data. Compounds 1-4, 6, 7, 9-16, and 20 displayed significant tyrosinase inhibitory activity. The most active compound, morachalcone A (12) (IC50, 0.013 μM), was 3000 times more active as a tyrosinase inhibitor than a positive control, kojic acid (IC50, 44.6 μM).

Acylphloroglucinol Biosynthesis in Strawberry Fruit1

PubMed Central

Song, Chuankui; Ring, Ludwig; Hoffmann, Thomas; Huang, Fong-Chin; Slovin, Janet; Schwab, Wilfried

2015-01-01

Phenolics have health-promoting properties and are a major group of metabolites in fruit crops. Through reverse genetic analysis of the functions of four ripening-related genes in the octoploid strawberry (Fragaria × ananassa), we discovered four acylphloroglucinol (APG)-glucosides as native Fragaria spp. fruit metabolites whose levels were differently regulated in the transgenic fruits. The biosynthesis of the APG aglycones was investigated by examination of the enzymatic properties of three recombinant Fragaria vesca chalcone synthase (FvCHS) proteins. CHS is involved in anthocyanin biosynthesis during ripening. The F. vesca enzymes readily catalyzed the condensation of two intermediates in branched-chain amino acid metabolism, isovaleryl-Coenzyme A (CoA) and isobutyryl-CoA, with three molecules of malonyl-CoA to form phlorisovalerophenone and phlorisobutyrophenone, respectively, and formed naringenin chalcone when 4-coumaroyl-CoA was used as starter molecule. Isovaleryl-CoA was the preferred starter substrate of FvCHS2-1. Suppression of CHS activity in both transient and stable CHS-silenced fruit resulted in a substantial decrease of APG glucosides and anthocyanins and enhanced levels of volatiles derived from branched-chain amino acids. The proposed APG pathway was confirmed by feeding isotopically labeled amino acids. Thus, Fragaria spp. plants have the capacity to synthesize pharmaceutically important APGs using dual functional CHS/(phloriso)valerophenone synthases that are expressed during fruit ripening. Duplication and adaptive evolution of CHS is the most probable scenario and might be generally applicable to other plants. The results highlight that important promiscuous gene function may be missed when annotation relies solely on in silico analysis. PMID:26169681

Crystal structures of three 1-[4-(4-bromo-but-oxy)-phen-yl] chalcone derivatives: (E)-1-[4-(4-bromo-but-oxy)-phen-yl]-3-phenyl-prop-2-en-1-one, (E)-1-[4-(4-bromo-but-oxy)-phen-yl]-3-(4-meth-oxy-phen-yl)prop-2-en-1-one and (E)-1-[4-(4-bromo-but-oxy)-phen-yl]-3-(3,4-di-meth-oxy-phen-yl)prop-2-en-1-one.

PubMed

Maragatham, Gunasekaran; Selvarani, Sivasamy; Rajakumar, Perumal; Lakshmi, Srinivasakannan

2017-07-01

The crystal structures of three chalcones with a bromo-substituted but-oxy side chain, viz . ( E )-1-[4-(4-bromo-but-oxy)-phen-yl]-3-phenyl-prop-2-en-1-one, C 19 H 19 BrO 2 , (I), ( E )-1-[4-(4-bromo-but-oxy)-phen-yl]-3-(4-meth-oxy-phen-yl)prop-2-en-1-one, C 20 H 21 BrO 3 , (II), and ( E )-1-[4-(4-bromo-but-oxy)-phen-yl]-3-(3,4-di-meth-oxy-phen-yl)prop-2-en-1-one, C 21 H 23 BrO 4 , (III), are reported. In all mol-ecules, the conformation of the keto group with respect to the olefinic bond is s - cis . Mol-ecules of (I) and (II) are nearly planar, while mol-ecule (III) is not planar. In the crystal of compounds (I) and (II), mol-ecules are linked into chains parallel to the c axis by C-H⋯π inter-actions. In the crystal of compound (III), mol-ecules are linked by a pairs of C-H⋯O hydrogen bonds, forming inversion dimers. Weak C-Br⋯π inter-actions are also observed in (III).

Introduction of a Chimeric Chalcone Synthase Gene into Petunia Results in Reversible Co-Suppression of Homologous Genes in trans.

PubMed Central

Napoli, C; Lemieux, C; Jorgensen, R

1990-01-01

We attempted to overexpress chalcone synthase (CHS) in pigmented petunia petals by introducing a chimeric petunia CHS gene. Unexpectedly, the introduced gene created a block in anthocyanin biosynthesis. Forty-two percent of plants with the introduced CHS gene produced totally white flowers and/or patterned flowers with white or pale nonclonal sectors on a wild-type pigmented background; none of hundreds of transgenic control plants exhibited such phenotypes. Progeny testing of one plant demonstrated that the novel color phenotype co-segregated with the introduced CHS gene; progeny without this gene were phenotypically wild type. The somatic and germinal stability of the novel color patterns was variable. RNase protection analysis of petal RNAs isolated from white flowers showed that, although the developmental timing of mRNA expression of the endogenous CHS gene was not altered, the level of the mRNA produced by this gene was reduced 50-fold from wild-type levels. Somatic reversion of plants with white flowers to phenotypically parental violet flowers was associated with a coordinate rise in the steady-state levels of the mRNAs produced by both the endogenous and the introduced CHS genes. Thus, in the altered white flowers, the expression of both genes was coordinately suppressed, indicating that expression of the introduced CHS gene was not alone sufficient for suppression of endogenous CHS transcript levels. The mechanism responsible for the reversible co-suppression of homologous genes in trans is unclear, but the erratic and reversible nature of this phenomenon suggests the possible involvement of methylation. PMID:12354959

Acylphloroglucinol Biosynthesis in Strawberry Fruit.

PubMed

Song, Chuankui; Ring, Ludwig; Hoffmann, Thomas; Huang, Fong-Chin; Slovin, Janet; Schwab, Wilfried

2015-11-01

Phenolics have health-promoting properties and are a major group of metabolites in fruit crops. Through reverse genetic analysis of the functions of four ripening-related genes in the octoploid strawberry (Fragaria × ananassa), we discovered four acylphloroglucinol (APG)-glucosides as native Fragaria spp. fruit metabolites whose levels were differently regulated in the transgenic fruits. The biosynthesis of the APG aglycones was investigated by examination of the enzymatic properties of three recombinant Fragaria vesca chalcone synthase (FvCHS) proteins. CHS is involved in anthocyanin biosynthesis during ripening. The F. vesca enzymes readily catalyzed the condensation of two intermediates in branched-chain amino acid metabolism, isovaleryl-Coenzyme A (CoA) and isobutyryl-CoA, with three molecules of malonyl-CoA to form phlorisovalerophenone and phlorisobutyrophenone, respectively, and formed naringenin chalcone when 4-coumaroyl-CoA was used as starter molecule. Isovaleryl-CoA was the preferred starter substrate of FvCHS2-1. Suppression of CHS activity in both transient and stable CHS-silenced fruit resulted in a substantial decrease of APG glucosides and anthocyanins and enhanced levels of volatiles derived from branched-chain amino acids. The proposed APG pathway was confirmed by feeding isotopically labeled amino acids. Thus, Fragaria spp. plants have the capacity to synthesize pharmaceutically important APGs using dual functional CHS/(phloriso)valerophenone synthases that are expressed during fruit ripening. Duplication and adaptive evolution of CHS is the most probable scenario and might be generally applicable to other plants. The results highlight that important promiscuous gene function may be missed when annotation relies solely on in silico analysis. © 2015 American Society of Plant Biologists. All Rights Reserved.

The synthetic α-bromo-2',3,4,4'-tetramethoxychalcone (α-Br-TMC) inhibits the JAK/STAT signaling pathway.

PubMed

Pinz, Sophia; Unser, Samy; Brueggemann, Susanne; Besl, Elisabeth; Al-Rifai, Nafisah; Petkes, Hermina; Amslinger, Sabine; Rascle, Anne

2014-01-01

Signal transducer and activator of transcription STAT5 and its upstream activating kinase JAK2 are essential mediators of cytokine signaling. Their activity is normally tightly regulated and transient. However, constitutive activation of STAT5 is found in numerous cancers and a driving force for malignant transformation. We describe here the identification of the synthetic chalcone α-Br-2',3,4,4'-tetramethoxychalcone (α-Br-TMC) as a novel JAK/STAT inhibitor. Using the non-transformed IL-3-dependent B cell line Ba/F3 and its oncogenic derivative Ba/F3-1*6 expressing constitutively activated STAT5, we show that α-Br-TMC targets the JAK/STAT pathway at multiple levels, inhibiting both JAK2 and STAT5 phosphorylation. Moreover, α-Br-TMC alters the mobility of STAT5A/B proteins in SDS-PAGE, indicating a change in their post-translational modification state. These alterations correlate with a decreased association of STAT5 and RNA polymerase II with STAT5 target genes in chromatin immunoprecipitation assays. Interestingly, expression of STAT5 target genes such as Cis and c-Myc was differentially regulated by α-Br-TMC in normal and cancer cells. While both genes were inhibited in IL-3-stimulated Ba/F3 cells, expression of the oncogene c-Myc was down-regulated and that of the tumor suppressor gene Cis was up-regulated in transformed Ba/F3-1*6 cells. The synthetic chalcone α-Br-TMC might therefore represent a promising novel anticancer agent for therapeutic intervention in STAT5-associated malignancies.

Phosphorus starvation induces post-transcriptional CHS gene silencing in Petunia corolla.

PubMed

Hosokawa, Munetaka; Yamauchi, Takayoshi; Takahama, Masayoshi; Goto, Mariko; Mikano, Sachiko; Yamaguchi, Yuki; Tanaka, Yoshiyuki; Ohno, Sho; Koeda, Sota; Doi, Motoaki; Yazawa, Susumu

2013-05-01

The corolla of Petunia 'Magic Samba' exhibits unstable anthocyanin expression depending on its phosphorus content. Phosphorus deficiency enhanced post-transcriptional gene silencing of chalcone synthase - A in the corolla. Petunia (Petunia hybrida) 'Magic Samba' has unstable red-white bicolored corollas that respond to nutrient deficiency. We grew this cultivar hydroponically using solutions that lacked one or several nutrients to identify the specific nutrient related to anthocyanin expression in corolla. The white area of the corolla widened under phosphorus (P)-deficient conditions. When the P content of the corolla grown under P-deficient conditions dropped to <2,000 ppm, completely white corollas continued to develop in >40 corollas until the plants died. Other elemental deficiencies had no clear effects on anthocyanin suppression in the corolla. After phosphate was resupplied to the P-deficient plants, anthocyanin was restored in the corollas. The expression of chalcone synthase-A (CHS-A) was suppressed in the white area that widened under P-suppressed conditions, whereas the expression of several other genes related to anthocyanin biosynthesis was enhanced more in the white area than in the red area. Reddish leaves and sepals developed under the P-deficient condition, which is a typical P-deficiency symptom. Two genes related to anthocyanin biosynthesis were enhanced in the reddish organs. Small interfering RNA analysis of CHS-A showed that the suppression resulted from post-transcriptional gene silencing (PTGS). Thus, it was hypothesized that the enhancement of anthocyanin biosynthetic gene expression due to P-deficiency triggered PTGS of CHS-A, which resulted in white corolla development.

Comparative Proteomic Analysis of the Graft Unions in Hickory (Carya cathayensis) Provides Insights into Response Mechanisms to Grafting Process

PubMed Central

Xu, Dongbin; Yuan, Huwei; Tong, Yafei; Zhao, Liang; Qiu, Lingling; Guo, Wenbin; Shen, Chenjia; Liu, Hongjia; Yan, Daoliang; Zheng, Bingsong

2017-01-01

Hickory (Carya cathayensis), a tree with high nutritional and economic value, is widely cultivated in China. Grafting greatly reduces the juvenile phase length and makes the large scale cultivation of hickory possible. To reveal the response mechanisms of this species to grafting, we employed a proteomics-based approach to identify differentially expressed proteins in the graft unions during the grafting process. Our study identified 3723 proteins, of which 2518 were quantified. A total of 710 differentially expressed proteins (DEPs) were quantified and these were involved in various molecular functional and biological processes. Among these DEPs, 341 were up-regulated and 369 were down-regulated at 7 days after grafting compared with the control. Four auxin-related proteins were down-regulated, which was in agreement with the transcription levels of their encoding genes. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the ‘Flavonoid biosynthesis’ pathway and ‘starch and sucrose metabolism’ were both significantly up-regulated. Interestingly, five flavonoid biosynthesis-related proteins, a flavanone 3-hyfroxylase, a cinnamate 4-hydroxylase, a dihydroflavonol-4-reductase, a chalcone synthase, and a chalcone isomerase, were significantly up-regulated. Further experiments verified a significant increase in the total flavonoid contents in scions, which suggests that graft union formation may activate flavonoid biosynthesis to increase the content of a series of downstream secondary metabolites. This comprehensive analysis provides fundamental information on the candidate proteins and secondary metabolism pathways involved in the grafting process for hickory. PMID:28496455

Targeting myeloid differentiation protein 2 by the new chalcone L2H21 protects LPS-induced acute lung injury.

PubMed

Zhang, Yali; Xu, Tingting; Wu, Beibei; Chen, Hongjin; Pan, Zheer; Huang, Yi; Mei, Liqin; Dai, Yuanrong; Liu, Xing; Shan, Xiaoou; Liang, Guang

2017-04-01

Acute inflammatory diseases are the leading causes of mortality in intensive care units. Myeloid differentiation 2 (MD-2) is required for recognizing lipopolysaccharide (LPS) by toll-like receptor 4 (TLR4), and represents an attractive therapeutic target for LPS-induced inflammatory diseases. In this study, we report a chalcone derivative, L2H21, as a new MD2 inhibitor, which could inhibit LPS-induced inflammation both in vitro and in vivo. We identify that L2H21 as a direct inhibitor of MD-2 by binding to Arg 90 and Tyr 102 residues in MD-2 hydrophobic pocket using a series of biochemical experiments, including surface plasmon response, molecular docking and amino acid mutation. L2H21 dose dependently inhibited LPS-induced inflammatory cytokine expression in primary macrophages. In mice with LPS intratracheal instillation, L2H21 significantly decreased LPS-induced pulmonary oedema, pathological changes in lung tissue, protein concentration increase in bronchoalveolar lavage fluid, inflammatory cells infiltration and inflammatory gene expression, accompanied with the decrease in pulmonary TLR4/MD-2 complex. Meanwhile, administration with L2H21 protects mice from LPS-induced mortality at a degree of 100%. Taken together, this study identifies a new MD2 inhibitor L2H21 as a promising candidate for the treatment of acute lung injury (ALI) and sepsis, and validates that inhibition of MD-2 is a potential therapeutic strategy for ALI. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Probing antioxidant activity of 2'-hydroxychalcones: crystal and molecular structures, in vitro antiproliferative studies and in vivo effects on glucose regulation.

PubMed

Rossi, Miriam; Caruso, Francesco; Crespi, Erica J; Pedersen, Jens Z; Nakano, Gail; Duong, Michelle; McKee, Celia; Lee, Sharon; Jiwrajka, Manasi; Caldwell, Charles; Baffour, Francis; Karlin, Dylan Alex; Lidoff, Genevieve; Leone, Stefano; Balducci, Valentina; Miler, Jaroslav; Incerpi, Sandra

2013-10-01

In order to better understand the antioxidant behavior of a series of polyphenolic 2'-hydroxychalcones, we describe the results of several chemical and biological studies, in vitro and in vivo. Single crystal X-ray methods elucidated their molecular structures and important intermolecular interactions such as H-bonding and molecular stacking in the crystal structures that contribute to our knowledge in explaining antioxidant activity. The results of experiments using the 1,1-diphenyl-2-dipicrylhydrazyl (DPPH) UV-vis spectroscopic method indicate that a hydroxyl group in position 5' induces the highest antioxidant activity. Consequently, 2,2',5'-trihydroxychalcone was selected for further study in vitro towards ROS scavenging in L-6 myoblasts and THP-1 human monocytes, where it shows an excellent antioxidant activity in a concentration range lower than that reported by most studies of related molecules. In addition, this chalcone shows a very selective activity: it inhibits the proliferation of leukemic cells, but it does not affect the normal L-6 myoblasts and human fibroblasts. In studying 2,2',5'-trihydroxychalcone's effect on weight gain and serum glucose and insulin levels in Zucker fatty (fa(-)/fa(-)) rats we found that supplementing the diet with a 10 mg/kg dose of this chalcone (3 times weekly) blunted the increase in glucose that co-occurs with weight gain over the 6-week treatment period. It is concluded that 2,2',5'-trihydroxychalcone has the potential to serve as a protective agent for some debilitating diseases. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Cinnamoylated chloroquine analogues: A new structural class of antimalarial agents.

PubMed

Gayam, Venkatareddy; Ravi, Subban

2017-07-28

A novel series of cinnamoylated chloroquine hybrid analogues were synthesized and evaluated as antimalarial agents. The trans cinnamic acid derivatives (3-8) were synthesized by utilizing substituted aldehydes and malanoic acid in DMF catalysed by DABCO. The final cinnamoylated chloroquine analogues (9-14) were synthesized by utilizing DCC coupling reagent. The amido chloroquine (17) was prepared from acid (16) and compound 2 in benzene using SOCl 2 as chlorinating agent. The corresponding ester (15) was prepared from 2-hydroxy acetophenone and 2-bromoacetates in actonitrile in presence of K 2 CO 3  as base followed by basic hydrolysis. The preparation of amide based chloroquine-chalcone analogues (18-22), were obtained by the combination of amido chloroquine (17) and aldehydes in 10% aq. KOH in methanol at room temperature. Further we prepared epichlorohydrin based chloroquine-chalcone analogues (25-28), by reacting the epoxide (24a, 24b and 24c) with 2 and methelenedioxy aniline. In vitro antimalarial activity against chloroquine sensitive strain 3D7, chloroquine resistant strain K1 of P. falciparum and in vitro cytotoxicity of compounds using VERO cell line was carried out. The synthesized molecules showed significant in vitro antimalarial activity especially against CQ resistant strain (K1). Among tested compounds, 13, 9 and 10 were found to be the most potent compounds of the series with IC 50 value of 44.06, 48.04 and 59.37 nM against chloroquine resistant K1 strain. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

The accumulation and localization of chalcone synthase in grapevine (Vitis vinifera L.).

PubMed

Wang, Huiling; Wang, Wei; Zhan, JiCheng; Yan, Ailing; Sun, Lei; Zhang, Guojun; Wang, Xiaoyue; Ren, Jiancheng; Huang, Weidong; Xu, Haiying

2016-09-01

Chalcone synthase (CHS, E.C.2.3.1.74) is the first committed enzyme in the flavonoid pathway. Previous studies have primarily focused on the cloning, expression and regulation of the gene at the transcriptional level. Little is yet known about the enzyme accumulation, regulation at protein level, as well as its localization in grapevine. In present study, the accumulation, tissue and subcellular localization of CHS in different grapevine tissues (Vitis vinifera L. Cabernet Sauvignon) were investigated via the techniques of Western blotting, immunohistochemical localization, immunoelectron microscopy and confocal microscopy. The results showed that CHS were mainly accumulated in the grape berry skin, leaves, stem tips and stem phloem, correlated with flavonoids accumulation. The accumulation of CHS is developmental dependent in grape berry skin and flesh. Immunohistochemical analysis revealed that CHS were primarily localized in the exocarp and vascular bundles of the fruits during berry development; in palisade, spongy tissues and vascular bundles of the leaves; in the primary phloem and pith ray in the stems; in the growth point, leaf primordium, and young leaves of leaf buds; and in the endoderm and primary phloem of grapevine roots. Furthermore, at the subcellular level, the cell wall, cytoplasm and nucleus localized patterns of CHS were observed in the grapevine vegetative tissue cells. Results above indicated that distribution of CHS in grapevine was organ-specific and tissue-specific. This work will provide new insight for the biosynthesis and regulation of diverse flavonoid compounds in grapevine. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Elevated Gene Expression in Chalcone Synthase Enzyme Suggests an Increased Production of Flavonoids in Skin and Synchronized Red Cell Cultures of North American Native Grape Berries

PubMed Central

Davis, Gina; Ananga, Anthony; Krastanova, Stoyanka; Sutton, Safira; Ochieng, Joel W.; Leong, Stephen

2012-01-01

Anthocyanins are antioxidants and are among the natural products synthesized via the flavonoid biosynthesis pathway. Anthocyanins have been recommended for dietary intake in the prevention of cardiovascular diseases, cancer, and age-related conditions such as Alzheimer's disease or dementia. With an increasingly aging population in many parts of the world, strategies for the commercial production of in vitro synchronized red cell cultures as natural antioxidants will be a significant contribution to human medicine. Red pigmented fruits such as grapes (Vitis sp.) are a major source of bioavailable anthocyanins and other polyphenols. Since the level of antioxidants varies among cultivars, this study is the first one that phytochemically and genetically characterizes native grape cultivars of North America to determine the optimal cultivar and berry cells for the production of anthocyanins as antioxidants. Using real-time PCR and bioinformatics approaches, we tested for the transcript expression of the chalcone synthase (CHS) gene, an enzyme involved in the flavonoid and anthocyanin biosynthesis pathway, in different parts of physiologically mature grape berries and in vitro synchronized red cells. A low level of expression was recorded in berry flesh, compared with an elevated expression in berry skins and in vitro synchronized red cells, suggesting increased production of flavonoids in skin and cell cultures. This preliminary study demonstrates the potential of functional genomics in natural products research as well as in systematic studies of North American native grapes, specifically in muscadine (Vitis rotundifolia). PMID:22364203

The diphenylether herbicide lactofen induces cell death and expression of defense-related genes in soybean.

PubMed

Graham, Madge Y

2005-12-01

Lactofen belongs to the diphenylether class of herbicides, which targets protoporphyrinogen oxidase, which in turn causes singlet oxygen generation. In tolerant plants like soybean (Glycine max), the chemical nonetheless causes necrotic patches called "bronzing" in contact areas. Here it is shown that such bronzing is accompanied by cell death, which was quantified from digital microscopic images using Assess Software. Cellular autofluorescence accompanied cell death, and a homolog of the cell death marker gene, Hsr203j, was induced by lactofen in treated soybean tissues. Thus, this form of chemically induced cell death shares some hallmarks of certain types of programmed cell death. In addition to the cell death phenotype, lactofen caused enhanced expressions of chalcone synthase and chalcone reductase genes, mainly in the exposed and immediately adjacent (proximal) cells. Furthermore, isoflavone synthase genes, which are wound inducible in soybean, were up-regulated by lactofen in both proximal and distal cell zones in minimally wounded cotyledons and further enhanced in wounded tissues. Moreover, if the wall glucan elicitor from Phytophthora sojae was present during lactofen treatment, the induction of isoflavone synthase was even more rapid. These results are consistent with the fact that lactofen triggers massive isoflavone accumulations and activates the capacity for glyceollin elicitation competency. In addition, lactofen induces late expression of a selective set of pathogenesis-related (PR) protein genes, including PR-1a, PR-5, and PR-10, mainly in treated proximal tissues. These various results are discussed in the context of singlet oxygen-induced responses and lactofen's potential as a disease resistance-inducing agent.

Modification of phenolic metabolism in soybean hairy roots through down regulation of chalcone synthase or isoflavone synthase.

PubMed

Lozovaya, Vera V; Lygin, Anatoliy V; Zernova, Olga V; Ulanov, Alexander V; Li, Shuxian; Hartman, Glen L; Widholm, Jack M

2007-02-01

Soybean hairy roots, transformed with the soybean chalcone synthase (CHS6) or isoflavone synthase (IFS2) genes, with dramatically decreased capacity to synthesize isoflavones were produced to determine what effects these changes would have on susceptibility to a fungal pathogen. The isoflavone and coumestrol concentrations were decreased by about 90% in most lines apparently due to gene silencing. The IFS2 transformed lines had very low IFS enzyme activity in microsomal fractions as measured by the conversion of naringenin to genistein. The CHS6 lines with decreased isoflavone concentrations had 5 to 20-fold lower CHS enzyme activities than the appropriate controls. Both IFS2 and CHS transformed lines accumulated higher concentrations of both soluble and cell wall bound phenolic acids compared to controls with higher levels found in the CHS6 lines indicating alterations in the lignin biosynthetic branch of the pathway. Induction of the soybean phytoalexin glyceollin, of which the precursor is the isoflavone daidzein, by the fungal pathogen Fusarium solani f. sp. glycines (FSG) that causes soybean sudden death syndrome (SDS) showed that the low isoflavone transformed lines did not accumulate glyceollin while the control lines did. The (iso)liquritigenin content increased upon FSG induction in the IFS2 transformed roots indicating that the pathway reactions before this point can control isoflavonoid synthesis. The lowest fungal growth rate on hairy roots was found on the FSG partially resistant control roots followed by the SDS sensitive control roots and the low isoflavone transformants. The results indicate the importance of phytoalexin synthesis in root resistance to the pathogen.

Effects of two 6-quinolinyl chalcones on the integrity of plasma membrane of Paracoccidioides brasiliensis.

PubMed

de Sá, Nívea P; Cisalpino, Patrícia S; Tavares, Luciana C; Espíndola, Leandro; Borelli, Beatriz M; Barbeira, Paulo Js; Cardoso Perdigão, Gabriele de Matos; Souza-Fagundes, Elaine M; Rosa, Carlos A; Pizzolatti, Moacir G; Johann, Susana

2017-03-01

Paracoccidioidomycosis is the most prevalent systemic mycosis in Latin America, yet few therapeutic options exist. Our aim was to search for new compounds with high efficacy, low toxicity, shorter treatment time and affordable cost. We studied two synthetic 6-quinolinyl chalcones, 3b and 3e, to determine their effects on VERO cells, antifungal activity, survival curve, interaction with other drugs and phenotypic effects against several isolates of Paracoccidioides spp. In this study, we verified that the compounds were not toxic, exhibited superior in vitro activity compared with that shown by trimethoprim-sulfamethoxazole, and after 5 days of treatment, decreased the fungal cell viability by approximately 70%. Additionally, no interactions were observed between the tested compounds and other drugs. We also found that these compounds induced morphological changes, such as shriveling of cells, fragmentation of the plasma membrane and cytoplasmic disorganization in vitro. The changes observed by microscopy assays corroborate the observation made with propidium iodide, where the number of cells stained with the compounds was higher than that observed after amphotericin B treatment. We observed an increase in the efflux of K + and a loss of intracellular contents in cells treated with 3b and 3e, confirming their effects on fungal membranes. However, damage to the membrane was not associated with a decrease in membrane ergosterol levels. The experimental evidences showed no direct indications of cellular wall damage caused by these compounds. Thus, these results confirm the antifungal potential of 3b and 3e against Paracoccidioides spp. with possible action on the membrane.

Inhibitory effects of compounds isolated from the dried branches and leaves of murta (Myrceugenia euosma) on lipid accumulation in 3T3-L1 cells.

PubMed

Oikawa, Naoki; Nobushi, Yasuhito; Wada, Taira; Sonoda, Kumiko; Okazaki, Yuzo; Tsutsumi, Shigetoshi; Park, Yong Kun; Kurokawa, Masahiko; Shimba, Shigeki; Yasukawa, Ken

2016-07-01

As obesity is a global health concern the demand for anti-obesity drugs is high. In this study, we investigated the anti-obesity effect of the dried branches and leaves of murta (Myrceugenia euosma Legrand, Myrtaceae). A methanol extract of the dried branches and leaves of murta inhibited adipogenesis in 3T3-L1 cells. Three known flavanones-cryptostrobin (1), pinocembrin (4), and 5,7-dihydroxy-6,8-dimethylflavanone (6), and three chalcones-2',6'-dihydroxy-3'-methyl-4'-methoxychalcone (2), pinostrobin chalcone (3), and 2',6'-dihydroxy-4'-methoxy-3',5'-dimethylchalcone (5) were isolated from the active fraction. Structures of these compounds were identified using various spectral data. Each of these compounds also inhibited adipogenesis in 3T3-L1 cells. In particular, compound 3 was a more potent inhibitor of triglyceride accumulation than the positive control berberine. Gene expression studies revealed that treatment of 3T3-L1 cells with 3 lowers the expression levels of CCAAT/enhancer-binding protein α and peroxisome proliferator activator γ2 during adipogenesis without affecting cell viability. Treatment of 3T3-L1 cells with 3 reduced the expression levels of mRNAs encoding sterol regulatory element-binding protein 1c and several lipogenic enzymes, including fatty acid synthase and stearoyl CoA desaturase-1. These results indicate that the methanol extract and compounds isolated from the dried branches and leaves of murta exert their anti-obesity effects through the inhibition of adipogenesis.

Synthesis, X-ray crystal structures and catecholase activity investigation of new chalcone ligands

NASA Astrophysics Data System (ADS)

Thabti, Salima; Djedouani, Amel; Rahmouni, Samra; Touzani, Rachid; Bendaas, Abderrahmen; Mousser, Hénia; Mousser, Abdelhamid

2015-12-01

The reaction of dehydroacetic acid DHA carboxaldehyde and RCHO derivatives (R = quinoleine-8-; indole-3-; pyrrol-2- and 4-(dimethylamino)phenyl - afforded four new chalcone ligands (4-hydroxy-6-methyl-3-[(2E)-3-quinolin-8-ylprop-2-enoyl]-2H-pyran-2-one) L1, (4-hydroxy-3-[(2E)-3-(1H-indol-3-yl)prop-2-enoyl]-6-methyl-2H-pyran-2-one) L2, (4-hydroxy-6-methyl-3-[(2E)-3-(1H-pyrrol-2-yl)prop-2-enoyl]-2H-pyran-2-one) L3, and (3-{(2E)-3-[4-(dimethylamino)phenyl]prop-2-enoyl}-4-hydroxy-6-methyl-2H-pyran-2-one) L4. L3 and L4 were characterized by X-ray crystallography. Molecules crystallize with four and two molecules in the asymmetric unit, respectively and adopt an E conformation about the Cdbnd C bond. Both structures are stabilized by an extended network O-H … O. Furthermore, N-H … O and C-H … O hydrogen bonds are observed in L3 and L4 structures, respectively. The in situ generated copper (II) complexes of the four compounds L1, L2, L3 and L4 were examined for their catalytic activities and were found to catalyze the oxidation reaction of catechol to o-quinone under atmospheric dioxygen. The rates of this oxidation depend on three parameters: ligand, ion salts and solvent nature and the combination L2[Cu (CH3COO)2] leads to the faster catalytic process.

A Malus Crabapple Chalcone Synthase Gene, McCHS, Regulates Red Petal Color and Flavonoid Biosynthesis

PubMed Central

Song, Tingting; Yao, Yuncong

2014-01-01

Chalcone synthase is a key and often rate-limiting enzyme in the biosynthesis of anthocyanin pigments that accumulate in plant organs such as flowers and fruits, but the relationship between CHS expression and the petal coloration level in different cultivars is still unclear. In this study, three typical crabapple cultivars were chosen based on different petal colors and coloration patterns. The two extreme color cultivars, ‘Royalty’ and ‘Flame’, have dark red and white petals respectively, while the intermediate cultivar ‘Radiant’ has pink petals. We detected the flavoniods accumulation and the expression levels of McCHS during petals expansion process in different cultivars. The results showed McCHS have their special expression patterns in each tested cultivars, and is responsible for the red coloration and color variation in crabapple petals, especially for color fade process in ‘Radiant’. Furthermore, tobacco plants constitutively expressing McCHS displayed a higher anthocyanins accumulation and a deeper red petal color compared with control untransformed lines. Moreover, the expression levels of several anthocyanin biosynthetic genes were higher in the transgenic McCHS overexpressing tobacco lines than in the control plants. A close relationship was observed between the expression of McCHS and the transcription factors McMYB4 and McMYB5 during petals development in different crabapple cultivars, suggesting that the expression of McCHS was regulated by these transcription factors. We conclude that the endogenous McCHS gene is a critical factor in the regulation of anthocyanin biosynthesis during petal coloration in Malus crabapple. PMID:25357207

Free volume dependent fluorescence property of PMMA composite: Positron annihilation studies

NASA Astrophysics Data System (ADS)

Ravindrachary, V.; Praveena, S. D.; Bhajantri, R. F.; Ismayil, Crasta, Vincent

2013-02-01

The free volume related fluorescence properties of chalcone chromophore [1-(4-methylphenyl)-3-(4-N, N, dimethylaminophenyl)-2-propen-1-one doped Poly(methyl methacrylate) have been studied using fluorescence spectroscopy and Positron Annihilation lifetime spectroscopy techniques. The fluorescence spectra show that the fluorescence behavior depends on the free volume dependent polymer microstructure and varies with dopant concentration with in the composite. The origin and variation of fluorescence is understood by twisted internal charge transfer state as well as free volume. The Positron annihilation study shows that the free volume related microstructure of the composite is vary with doping level.

Synthesis, structure and in vitro cytostatic activity of ferrocene-Cinchona hybrids.

PubMed

Kocsis, László; Szabó, Ildikó; Bősze, Szilvia; Jernei, Tamás; Hudecz, Ferenc; Csámpai, Antal

2016-02-01

Exploring copper(I)- and ruthenium(II)-catalyzed azide-alkyne cycloadditions and a Sonogashira protocol, novel cytostatic ferrocene-cinchona hybrids were synthetized displaying significant in vitro activity on HepG-2 and HT-29 cells. Preliminary SAR studies disclosed that compounds incorporating linkers with 1,2,3-triazole and chalchone residues can be considered as promising lead structures. According to the best of our knowledge this is the first letter on the incorporation of ferrocene nucleus in the reputed cinchona family via triazole and chalcone linkers with established pharmaceutical profile. Copyright © 2015 Elsevier Ltd. All rights reserved.

Synthesis and biological evaluation of (E)-1-(substituted)-3-phenylprop-2-en-1-ones bearing rhodanines as potent anti-microbial agents.

PubMed

Song, Ming-Xia; Deng, Xian-Qing; Li, Ya-Ru; Zheng, Chang-Ji; Hong, Lan; Piao, Hu-Ri

2014-10-01

Herein, we report the design, syntheses and in vitro anti-microbial activity of two series of rhodanines with chalcone moiety. Anti-microbial tests showed that some of the synthesized compounds exhibited good inhibition (MIC = 1-8 µg/mL) against multi-drug-resistant Gram-positive organisms, including methicillin resistant and quinolone-resistant Staphylococcus aureus, in which the compound 4g was found to be the most potent with minimum inhibitory concentration (MIC) value of 1 µg/mL against two methicillin-resistant S. aureus.

The Synthetic α-Bromo-2′,3,4,4′-Tetramethoxychalcone (α-Br-TMC) Inhibits the JAK/STAT Signaling Pathway

PubMed Central

Brueggemann, Susanne; Besl, Elisabeth; Al-Rifai, Nafisah; Petkes, Hermina; Amslinger, Sabine; Rascle, Anne

2014-01-01

Signal transducer and activator of transcription STAT5 and its upstream activating kinase JAK2 are essential mediators of cytokine signaling. Their activity is normally tightly regulated and transient. However, constitutive activation of STAT5 is found in numerous cancers and a driving force for malignant transformation. We describe here the identification of the synthetic chalcone α-Br-2′,3,4,4′-tetramethoxychalcone (α-Br-TMC) as a novel JAK/STAT inhibitor. Using the non-transformed IL-3-dependent B cell line Ba/F3 and its oncogenic derivative Ba/F3-1*6 expressing constitutively activated STAT5, we show that α-Br-TMC targets the JAK/STAT pathway at multiple levels, inhibiting both JAK2 and STAT5 phosphorylation. Moreover, α-Br-TMC alters the mobility of STAT5A/B proteins in SDS-PAGE, indicating a change in their post-translational modification state. These alterations correlate with a decreased association of STAT5 and RNA polymerase II with STAT5 target genes in chromatin immunoprecipitation assays. Interestingly, expression of STAT5 target genes such as Cis and c-Myc was differentially regulated by α-Br-TMC in normal and cancer cells. While both genes were inhibited in IL-3-stimulated Ba/F3 cells, expression of the oncogene c-Myc was down-regulated and that of the tumor suppressor gene Cis was up-regulated in transformed Ba/F3-1*6 cells. The synthetic chalcone α-Br-TMC might therefore represent a promising novel anticancer agent for therapeutic intervention in STAT5-associated malignancies. PMID:24595334

Molecular characterization and functional analysis of chalcone synthase from Syringa oblata Lindl. in the flavonoid biosynthetic pathway.

PubMed

Wang, Yu; Dou, Ying; Wang, Rui; Guan, Xuelian; Hu, Zenghui; Zheng, Jian

2017-11-30

The flower color of Syringa oblata Lindl., which is often modulated by the flavonoid content, varies and is an important ornamental feature. Chalcone synthase (CHS) catalyzes the first key step in the flavonoid biosynthetic pathway. However, little is known about the role of S. oblata CHS (SoCHS) in flavonoid biosynthesis in this species. Here, we isolate and analyze the cDNA (SoCHS1) that encodes CHS in S. oblata. We also sought to analyzed the molecular characteristics and function of flavonoid metabolism by SoCHS1. We successfully isolated the CHS-encoding genomic DNA (gDNA) in S. oblata (SoCHS1), and the gene structural analysis indicated it had no intron. The opening reading frame (ORF) sequence of SoCHS1 was 1170bp long and encoded a 389-amino acid polypeptide. Multiple sequence alignment revealed that both the conserved CHS active site residues and CHS signature sequence were in the deduced amino acid sequence of SoCHS1. Crystallographic analysis revealed that the protein structure of SoCHS1 is highly similar to that of FnCHS1 in Freesia hybrida. The quantitative real-time polymerase chain reaction (PCR) performed to detect the SoCHS1 transcript expression levels in flowers, and other tissues revealed the expression was significantly correlated with anthocyanin accumulation during flower development. The ectopic expression results of Nicotiana tabacum showed that SoCHS1 overexpression in transgenic tobacco changed the flower color from pale pink to pink. In conclusion, these results suggest that SoCHS1 plays an essential role in flavonoid biosynthesis in S. oblata, and could be used to modify flavonoid components in other plant species. Copyright © 2017. Published by Elsevier B.V.

Anti-inflammatory, Antioxidant and Antimicrobial Activity Characterization and Toxicity Studies of Flowers of "Jarilla", a Medicinal Shrub from Argentina.

PubMed

Moreno, Alejandra; Nuño, Gabriela; Cuello, Soledad; Sayago, Jorge E; Alberto, María Rosa; Zampini, Catiana; Isla, María Inés

2015-06-01

Zuccagnia punctata Cav. (Fabaceae) is an Argentine medicinal aromatic shrub (jarilla pispito, puspus, lata and jarilla macho). The chalcones were identified as pigments responsible for the yellow color of the flowers. Hydroethanolic extracts were obtained both from fresh flowers and from flowers dried by lyophilization. The extracts were standardized by their phenolic and flavonoids content. Their fingerprints by HPLC-DAD indicated the presence of two chalcones as major compounds (2',4'-dihydroxychalcone and 2',4'-dihydroxy-3'-methoxychalcone). Both extracts showed the same total phenolic, non-flavonoid phenolic and flavonoid phenolic content and their phenolic profiles were similar. The polyphenolic extracts exhibited antioxidant (free radical scavenging and inhibitory activity on lipoperoxidation) and anti-inflammatory (inhibition of lipoxygenase and cyclooxygenase enzymes) activities. The flower extracts were active against six Candida species with MIC values between 60 and 120 μg GAE x mL(-1) and were also active on methicillin-resistant Staphylococcus aureus (MIC: 250 μg GAE x mL(-1)) and Enterococcus faecalis (MIC: 500 μg GAE x mL(-1)). The extracts were neither toxic (Artemia salina test) nor mutagenic (Ames test). Jarilla flowers could be considered as a new dietary supplement that could help to prevent pathologies associated with oxidative stress and the polyphenolic extract obtained from them could be considered as a standardized phytotherapeutic product with antimicrobial, antioxidant and anti-inflammatory activities. The aim of this work was to determine the pigments responsible for the yellow color of the flowers of Z. punctata and to evaluate the functional properties of the polyphenolic extract of the flowers. The toxicity (Artemia salina) and mutagenic activity (Ames test) of the extract were also evaluated.

Isolation and identification of antibacterial and cytotoxic compounds from the leaves of Muntingia calabura L.

PubMed

Sufian, Adila S; Ramasamy, Kalavathy; Ahmat, Norizan; Zakaria, Zainul A; Yusof, M Izwan M

2013-03-07

Muntingia calabura (Elaeocarpaceae) is one of the most common roadside trees in Malaysia. Its leaves, barks, flowers and roots have been used as a folk remedy for the treatment of fever, incipient cold, liver disease, as well as an antiseptic agent in Southeast Asia. The aim of this study is to isolate and identify the antibacterial and cytotoxic compounds from the leaves of Muntingia calabura L. Antibacterial and cytotoxic activities were determined by micro-broth dilution and MTT assays, respectively. Seven fractions (F1-F7), three flavones and a chalcone were isolated from the active EtOAc extract using bioassay-guided screening. The structures of four compounds were elucidated by spectroscopic methods and compared with published data. The compounds were further tested for their antibacterial and cytotoxic activities. Three flavones and a chalcone [5,7-dihydroxy-3,8-dimethoxyflavone (1), 2',4'-dihydroxychalcone (2), 5-hydroxy-3,7-dimethoxyflavone (3) and 3,5,7-trihydroxy-8-methoxyflavone (4)] were isolated from the active fraction F5 of EtOAc extract. Compounds 1 and 3 were isolated for the first time from Muntingia calabura L. Antibacterial activity indicates that compound 2 exhibited the most significant activity with MIC value of 50 μg/mL and 100 μg/mL against MSSA and MRSA, respectively. Cytotoxic activity indicates that compounds 2 and 3 exhibited very strong activity against HL60 with IC50 values of 3.43 μg/mL and 3.34 μg/mL, respectively. The antibacterial activity of the leaves of Muntingia calabura L. is ascribable to the active compound 2 while the cytotoxic activity is ascribable to the active compounds 2 and 3. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Differential inductions of phenylalanine ammonia-lyase and chalcone synthase during wounding, salicylic acid treatment, and salinity stress in safflower, Carthamus tinctorius

PubMed Central

Dehghan, Sara; Sadeghi, Mahnaz; Pöppel, Anne; Fischer, Rainer; Lakes-Harlan, Reinhard; Kavousi, Hamid Reza; Vilcinskas, Andreas; Rahnamaeian, Mohammad

2014-01-01

Safflower (Carthamus tinctorius L.) serves as a reference dicot for investigation of defence mechanisms in Asteraceae due to abundant secondary metabolites and high resistance/tolerance to environmental stresses. In plants, phenylpropanoid and flavonoid pathways are considered as two central defence signalling cascades in stress conditions. Here, we describe the isolation of two major genes in these pathways, CtPAL (phenylalanine ammonia-lyase) and CtCHS (chalcone synthase) in safflower along with monitoring their expression profiles in different stress circumstances. The aa (amino acid) sequence of isolated region of CtPAL possesses the maximum identity up to 96% to its orthologue in Cynara scolymus, while that of CtCHS retains the highest identity to its orthologue in Callistephus chinensis up to 96%. Experiments for gene expression profiling of CtPAL and CtCHS were performed after the treatment of seedlings with 0.1 and 1 mM SA (salicylic acid), wounding and salinity stress. The results of semi-quantitative RT–PCR revealed that both CtPAL and CtCHS genes are further responsive to higher concentration of SA with dissimilar patterns. Regarding wounding stress, CtPAL gets slightly induced upon injury at 3 hat (hours after treatment) (hat), whereas CtCHS gets greatly induced at 3 hat and levels off gradually afterward. Upon salinity stress, CtPAL displays a similar expression pattern by getting slightly induced at 3 hat, but CtCHS exhibits a biphasic expression profile with two prominent peaks at 3 and 24 hat. These results substantiate the involvement of phenylpropanoid and particularly flavonoid pathways in safflower during wounding and especially salinity stress. PMID:24865400

Functional Promiscuity of Two Divergent Paralogs of Type III Plant Polyketide Synthases1

PubMed Central

Pandith, Shahzad A.; Dhar, Niha; Bhat, Wajid Waheed; Kushwaha, Manoj; Gupta, Ajai P.; Shah, Manzoor A.; Vishwakarma, Ram

2016-01-01

Plants effectively defend themselves against biotic and abiotic stresses by synthesizing diverse secondary metabolites, including health-protective flavonoids. These display incredible chemical diversity and ubiquitous occurrence and confer impeccable biological and agricultural applications. Chalcone synthase (CHS), a type III plant polyketide synthase, is critical for flavonoid biosynthesis. It catalyzes acyl-coenzyme A thioesters to synthesize naringenin chalcone through a polyketidic intermediate. The functional divergence among the evolutionarily generated members of a gene family is pivotal in driving the chemical diversity. Against this backdrop, this study was aimed to functionally characterize members of the CHS gene family from Rheum emodi, an endangered and endemic high-altitude medicinal herb of northwestern Himalayas. Two full-length cDNAs (1,179 bp each), ReCHS1 and ReCHS2, encoding unique paralogs were isolated and characterized. Heterologous expression and purification in Escherichia coli, bottom-up proteomic characterization, high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry analysis, and enzyme kinetic studies using five different substrates confirmed their catalytic potential. Phylogenetic analysis revealed the existence of higher synonymous mutations in the intronless divergents of ReCHS. ReCHS2 displayed significant enzymatic efficiency (Vmax/Km) with different substrates. There were significant spatial and altitudinal variations in messenger RNA transcript levels of ReCHSs correlating positively with metabolite accumulation. Furthermore, the elicitations in the form of methyl jasmonate, salicylic acid, ultraviolet B light, and wounding, chosen on the basis of identified cis-regulatory promoter elements, presented considerable differences in the transcript profiles of ReCHSs. Taken together, our results demonstrate differential propensities of CHS paralogs in terms of the accumulation of flavonoids and their relative substrate selectivities. PMID:27268960

A chalcone isomerase-like protein enhances flavonoid production and flower pigmentation.

PubMed

Morita, Yasumasa; Takagi, Kyoko; Fukuchi-Mizutani, Masako; Ishiguro, Kanako; Tanaka, Yoshikazu; Nitasaka, Eiji; Nakayama, Masayoshi; Saito, Norio; Kagami, Takashi; Hoshino, Atsushi; Iida, Shigeru

2014-04-01

Flavonoids are major pigments in plants, and their biosynthetic pathway is one of the best-studied metabolic pathways. Here we have identified three mutations within a gene that result in pale-colored flowers in the Japanese morning glory (Ipomoea nil). As the mutations lead to a reduction of the colorless flavonoid compound flavonol as well as of anthocyanins in the flower petal, the identified gene was designated enhancer of flavonoid production (EFP). EFP encodes a chalcone isomerase (CHI)-related protein classified as a type IV CHI protein. CHI is the second committed enzyme of the flavonoid biosynthetic pathway, but type IV CHI proteins are thought to lack CHI enzymatic activity, and their functions remain unknown. The spatio-temporal expression of EFP and structural genes encoding enzymes that produce flavonoids is very similar. Expression of both EFP and the structural genes is coordinately promoted by genes encoding R2R3-MYB and WD40 family proteins. The EFP gene is widely distributed in land plants, and RNAi knockdown mutants of the EFP homologs in petunia (Petunia hybrida) and torenia (Torenia hybrida) had pale-colored flowers and low amounts of anthocyanins. The flavonol and flavone contents in the knockdown petunia and torenia flowers, respectively, were also significantly decreased, suggesting that the EFP protein contributes in early step(s) of the flavonoid biosynthetic pathway to ensure production of flavonoid compounds. From these results, we conclude that EFP is an enhancer of flavonoid production and flower pigmentation, and its function is conserved among diverse land plant species. © 2014 The Authors The Plant Journal © 2014 John Wiley & Sons Ltd.

Light quality affects flavonoid production and related gene expression in Cyclocarya paliurus.

PubMed

Liu, Yang; Fang, Shengzuo; Yang, Wanxia; Shang, Xulan; Fu, Xiangxiang

2018-02-01

Understanding the responses of plant growth and secondary metabolites to differential light conditions is very important to optimize cultivation conditions of medicinal woody plants. As a highly valued and multiple function tree species, Cyclocarya paliurus is planted and managed for timber production and medical use. In this study, LED-based light including white light (WL), blue light (BL), red light (RL), and green light (GL) were used to affect leaf biomass production, flavonoid accumulation and related gene expression of one-year C. paliurus seedlings in controlled environments. After the treatments of 60 days, the highest leaf biomass appeared in the treatment of WL, while the lowest leaf biomass was found under GL. Compared to WL, the total flavonoid contents of C. paliurus leaves were significantly higher in BL, RL, and GL, but the highest values of selected flavonoids (kaempferol, isoquercitrin and quercetin) were observed under BL. Furthermore, the greatest yields of total and selected flavonoids in C. paliurus leaves per seedling were also achieved under BL, indicating that blue light was effective for inducing the production of flavonoids in C. paliurus leaves. Pearson's correlation analysis showed that there were significantly positive correlations between leaf flavonoid content and relative gene expression of key enzymes (phenylalanine ammonia lyase, PAL; 4-coumaroyl CoA-ligase, 4CL; and chalcone synthase, CHS) in the upstream, which converting phenylalanine into the flavonoid skeleton of tetrahydroxy chalcone. It is concluded that manipulating light quality may be potential mean to achieve the highest yields of flavonoids in C. paliurus cultivation, however this needs to be further verified by more field trials. Copyright © 2018 Elsevier B.V. All rights reserved.

A wild ‘albino’ bilberry (Vaccinium myrtillus L.) from Slovenia shows three bottlenecks in the anthocyanin pathway and significant differences in the expression of several regulatory genes compared to the common blue berry type

PubMed Central

Veberic, Robert; Slatnar, Ana; Koron, Darinka; Miosic, Silvija; Chen, Ming-Hui; Haselmair-Gosch, Christian; Halbwirth, Heidi; Mikulic-Petkovsek, Maja

2017-01-01

Relative expressions of structural genes and a number of transcription factors of the anthocyanin pathway relevant in Vaccinium species, and related key enzyme activities were compared with the composition and content of metabolites in skins of ripe fruits of wild albino and blue bilberry (Vaccinium myrtillus) found in Slovenia. Compared to the common blue type, the albino variant had a 151-fold lower total anthocyanin and a 7-fold lower total phenolic content in their berry skin, which correlated with lower gene expression of flavonoid 3-O-glycosyltransferase (FGT; 33-fold), flavanone 3-hydroxylase (FHT; 18-fold), anthocyanidin synthase (ANS; 11-fold), chalcone synthase (CHS, 7.6-fold) and MYBPA1 transcription factor (22-fold). The expression of chalcone isomerase (CHI), dihydroflavonol 4-reductase (DFR), leucoanthocyanidin reductase (LAR), anthocyanidin reductase (ANR) and MYBC2 transcription factor was reduced only by a factor of 1.5–2 in the albino berry skins, while MYBR3 and flavonoid 3’,5’-hydroxylase (F3’5’H) were increased to a similar extent. Expression of the SQUAMOSA class transcription factor TDR4, in contrast, was independent of the color type and does therefore not seem to be correlated with anthocyanin formation in this variant. At the level of enzymes, significantly lower FHT and DFR activities, but not of phenylalanine ammonia-lyase (PAL) and CHS/CHI, were observed in the fruit skins of albino bilberries. A strong increase in relative hydroxycinnamic acid derivative concentrations indicates the presence of an additional bottleneck in the general phenylpropanoid pathway at a so far unknown step between PAL and CHS. PMID:29272302

Downregulation of putative UDP-glucose: flavonoid 3-O-glucosyltransferase gene alters flower coloring in Phalaenopsis.

PubMed

Chen, Wen-Huei; Hsu, Chi-Yin; Cheng, Hao-Yun; Chang, Hsiang; Chen, Hong-Hwa; Ger, Mang-Jye

2011-06-01

Anthocyanin is the primary pigment contributing to red, violet, and blue flower color formation. The solubility of anthocyanins is enhanced by UDP glucose: flavonoid 3-O-glucosyltransferase (UFGT) through transfer of the glucosyl moiety from UDP-glucose to 3-hydroxyl group to produce the first stable pigments. To assess the possibility that UFGT is involved in the flower color formation in Phalaenopsis, the transcriptional activities of PeUFGT3, and other flower color-related genes in developing red or white flower buds were examined using RT-PCR analysis. In contrast with chalcone synthase, chalcone isomerase, and anthocyanidin synthase genes, PeUFGT3 transcriptional activity was higher expressed in the red color of Phalaenopsis cultivars. In the red labellum of Phalaenopsis 'Luchia Lady', PeUFGT3 also showed higher expression levels than that in the white perianth. PeUFGT3 was predominantly expressed in the red region of flower among various Phalaenopsis cultivars. To investigate the role of PeUFGT3 in red flower color formation, PeUFGT3 was specifically knocked down using RNA interference technology via virus inducing gene silencing in Phalaenopsis. The PeUFGT3-suppressed Phalaenopsis exhibited various levels of flower color fading that was well correlated with the extent of reduced level of PeUFGT3 transcriptional activity. Furthermore, there was a significant decrease in anthocyanin content in the PeUFGT3-suppressed Phalaenopsis flowers. The decrease of anthocyanin content due to PeUFGT3 gene silencing possibly caused the faded flower color in PeUFGT3-suppressed Phalaenopsis. Consequently, these results suggested that the glycosylation-related gene PeUFGT3 plays a critical role in red color formation in Phalaenopsis.

Gibberellic Acid Regulates Chalcone Synthase Gene Transcription in the Corolla of Petunia hybrida 1

PubMed Central

Weiss, David; van Blokland, Rik; Kooter, Jan M.; Mol, Joseph N. M.; van Tunen, Arjen J.

1992-01-01

The pigmentation of Petunia hybrida corollas is regulated by gibberellic acid (GA3). It controls the increase of flavonoid enzyme levels and their corresponding mRNAs. We have used an in vitro culture system for corollas to study the regulatory role of GA3 in the expression of flavonoid genes. By determining steady-state mRNA levels, we show that the accumulation of chalcone synthase (chs) mRNA in young corollas is dependent on the presence of both sucrose and GA3 in the culture medium. Whereas sucrose had a general metabolic effect on gene expression, the stimulatory role of GA3 was specific. Analysis of nascent transcripts in isolated corolla nuclei showed that changes in steady-state chs mRNA levels correlated very well with changes in the transcription rate. We therefore conclude that GA3 controls the expression of chs at the transcriptional level. Preculturing the corollas in sucrose medium without GA3 resulted in a lower chs mRNA level. The expression could be reinduced by the addition of GA3. The hormone is thus required for the induction but also for the maintenance of chs transcription. The delayed reinduction of chs expression, the lag time in the kinetics of chs mRNA accumulation, and the inhibitory effect of cycloheximide on the action of GA3 suggest that GA3 controls chs transcription in an indirect manner. Our data support a model in which GA3 induces the production of a regulatory protein such as a receptor or a trans-acting factor that is directly involved in chs transcription. ImagesFigure 1Figure 2Figure 3Figure 4Figure 5Figure 6 PMID:16668613

Proteomic analysis of tea plants (Camellia sinensis) with purple young shoots during leaf development

PubMed Central

Zhou, Qiongqiong; Chen, Zhidan; Lee, Jinwook; Li, Xinghui; Sun, Weijiang

2017-01-01

Tea products made from purple leaves are highly preferred by consumers due to the health benefits. This study developed a proteome reference map related to color changes during leaf growth in tea (Camellia sinensis) plant with purple young shoots using two-dimensional electrophoresis (2-DE). Forty-six differentially expressed proteins were detected in the gel and successfully identified by using MALDI-TOF/TOF-MS. The pronounced changes in the proteomic profile between tender purple leaves (TPL) and mature green leaves (MGL) included: 1) the lower activity of proteins associated with CO2 assimilation, energy metabolism and photo flux efficiency and higher content of anthocyanins in TPL than those in MGL may protect tender leaves against photo-damage; 2) the higher abundance of chalcone synthase (CHS), chalcone isomerase (CHI) and flavonol synthase (FLS) likely contributes to the synthesis of anthocyanins, catechins and flavonols in TPL tissues; 3) higher abundance of stress response proteins, such as glutathione S-transferases (GST) and phospholipid hydroperoxide glutathione peroxidase (PHGPx), could enhance the tolerance of TPL tissues to adverse condition in; and 4) the increased abundance of proteins related to protein synthesis, nucleic acids and cell wall proteins should be beneficial for the proliferation and expansion of leaf cell in TPL tissues. qPCR analysis showed that the expression of differentially abundant proteins was regulated at the transcriptional level. Therefore, the results indicated that higher abundance of CHI and CHS may account for the production of the purple-shoot phenotype in Wuyiqizhong 18 and thereby, enhancing the anthocyanin biosynthesis. The higher abundance of glutamine synthetase (GS) proteins related to the theanine biosynthesis may improve the flavor of tea products from TPL materials. Thus, this work should help to understand the molecular mechanisms underlying the changes in leaf color alteration. PMID:28520776

A wild 'albino' bilberry (Vaccinium myrtillus L.) from Slovenia shows three bottlenecks in the anthocyanin pathway and significant differences in the expression of several regulatory genes compared to the common blue berry type.

PubMed

Zorenc, Zala; Veberic, Robert; Slatnar, Ana; Koron, Darinka; Miosic, Silvija; Chen, Ming-Hui; Haselmair-Gosch, Christian; Halbwirth, Heidi; Mikulic-Petkovsek, Maja

2017-01-01

Relative expressions of structural genes and a number of transcription factors of the anthocyanin pathway relevant in Vaccinium species, and related key enzyme activities were compared with the composition and content of metabolites in skins of ripe fruits of wild albino and blue bilberry (Vaccinium myrtillus) found in Slovenia. Compared to the common blue type, the albino variant had a 151-fold lower total anthocyanin and a 7-fold lower total phenolic content in their berry skin, which correlated with lower gene expression of flavonoid 3-O-glycosyltransferase (FGT; 33-fold), flavanone 3-hydroxylase (FHT; 18-fold), anthocyanidin synthase (ANS; 11-fold), chalcone synthase (CHS, 7.6-fold) and MYBPA1 transcription factor (22-fold). The expression of chalcone isomerase (CHI), dihydroflavonol 4-reductase (DFR), leucoanthocyanidin reductase (LAR), anthocyanidin reductase (ANR) and MYBC2 transcription factor was reduced only by a factor of 1.5-2 in the albino berry skins, while MYBR3 and flavonoid 3',5'-hydroxylase (F3'5'H) were increased to a similar extent. Expression of the SQUAMOSA class transcription factor TDR4, in contrast, was independent of the color type and does therefore not seem to be correlated with anthocyanin formation in this variant. At the level of enzymes, significantly lower FHT and DFR activities, but not of phenylalanine ammonia-lyase (PAL) and CHS/CHI, were observed in the fruit skins of albino bilberries. A strong increase in relative hydroxycinnamic acid derivative concentrations indicates the presence of an additional bottleneck in the general phenylpropanoid pathway at a so far unknown step between PAL and CHS.

Production of 7-O-Methyl Aromadendrin, a Medicinally Valuable Flavonoid, in Escherichia coli

PubMed Central

Malla, Sailesh; Koffas, Mattheos A. G.; Kazlauskas, Romas J.

2012-01-01

7-O-Methyl aromadendrin (7-OMA) is an aglycone moiety of one of the important flavonoid-glycosides found in several plants, such as Populus alba and Eucalyptus maculata, with various medicinal applications. To produce such valuable natural flavonoids in large quantity, an Escherichia coli cell factory has been developed to employ various plant biosynthetic pathways. Here, we report the generation of 7-OMA from its precursor, p-coumaric acid, in E. coli for the first time. Primarily, naringenin (NRN) (flavanone) synthesis was achieved by feeding p-coumaric acid and reconstructing the plant biosynthetic pathway by introducing the following structural genes: 4-coumarate–coenzyme A (CoA) ligase from Petroselinum crispum, chalcone synthase from Petunia hybrida, and chalcone isomerase from Medicago sativa. In order to increase the availability of malonyl-CoA, a critical precursor of 7-OMA, genes for the acyl-CoA carboxylase α and β subunits (nfa9890 and nfa9940), biotin ligase (nfa9950), and acetyl-CoA synthetase (nfa3550) from Nocardia farcinica were also introduced. Thus, produced NRN was hydroxylated at position 3 by flavanone-3-hydroxylase from Arabidopsis thaliana, which was further methylated at position 7 to produce 7-OMA in the presence of 7-O-methyltransferase from Streptomyces avermitilis. Dihydrokaempferol (DHK) (aromadendrin) and sakuranetin (SKN) were produced as intermediate products. Overexpression of the genes for flavanone biosynthesis and modification pathways, along with malonyl-CoA overproduction in E. coli, produced 2.7 mg/liter (8.9 μM) 7-OMA upon supplementation with 500 μM p-coumaric acid in 24 h, whereas the strain expressing only the flavanone modification enzymes yielded 30 mg/liter (99.2 μM) 7-OMA from 500 μM NRN in 24 h. PMID:22101053

Advance in dietary polyphenols as aldose reductases inhibitors: structure-activity relationship aspect.

PubMed

Xiao, Jianbo; Ni, Xiaoling; Kai, Guoyin; Chen, Xiaoqing

2015-01-01

The dietary polyphenols as aldose reductases inhibitors (ARIs) have attracted great interest among researchers. The aim of this review is to give an overview of the research reports on the structure-activity relationship of dietary polyphenols inhibiting aldose reductases (AR). The molecular structures influence the inhibition of the following: (1) The methylation and methoxylation of the hydroxyl group at C3, C3', and C4' of flavonoids decreased or little affected the inhibitory potency. However, the methylation and methoxylation of the hydroxyl group at C5, C6, and C8 significantly enhanced the inhibition. Moreover, the methylation and methoxylation of C7-OH influence the inhibitory activity depending on the substitutes on rings A and B of flavonoids. (2) The glycosylation on 3-OH of flavonoids significantly increased or little affected the inhibition. However, the glycosylation on 7-OH and 4'-OH of flavonoids significantly decreased the inhibition. (3) The hydroxylation on A-ring of flavones and isoflavones, especially at positions 5 and 7, significantly improved the inhibition and the hydroxylation on C3' and C4' of B-ring of flavonoids remarkably enhanced the inhibition; however, the hydroxylation on the ring C of flavones significantly weakened the inhibition. (4) The hydrogenation of the C2=C3 double bond of flavones reduced the inhibition. (5) The hydrogenation of α=β double bond of stilbenes hardly affected the inhibition and the hydroxylation on C3' of stilbenes decreased the inhibition. Moreover, the methylation of the hydroxyl group of stilbenes obviously reduced the activity. (6) The hydroxylation on C4 of chalcone significantly increased the inhibition and the methylation on C4 of chalcone remarkably weakened the inhibition.

Interplay between the chalcone cardamonin and selenium in the biosynthesis of Nrf2-regulated antioxidant enzymes in intestinal Caco-2 cells.

PubMed

De Spirt, Silke; Eckers, Anna; Wehrend, Carina; Micoogullari, Mustafa; Sies, Helmut; Stahl, Wilhelm; Steinbrenner, Holger

2016-02-01

Selenoenzymes and nuclear factor erythroid 2-related factor 2 (Nrf2)-regulated phase II enzymes comprise key components of the cellular redox and antioxidant systems, which show multiple interrelations. Deficiency of the micronutrient selenium (Se) and impaired biosynthesis of selenoproteins have been reported to result in induction of Nrf2 target genes. Conversely, transcription of the selenoenzymes glutathione peroxidase 2 (GPx2) and thioredoxin reductase 1 (TrxR1) is up-regulated upon Nrf2 activation. Here, we have studied the interplay between Se and the secondary plant metabolite cardamonin, an Nrf2-activating chalcone, in the regulation of Nrf2-controlled antioxidant enzymes. Se-deficient and Se-repleted (sodium selenite-supplemented) human intestinal Caco-2 cells were exposed to cardamonin. Uptake of cardamonin by the Caco-2 cells was independent of their Se status. Cardamonin strongly induced gene expression of GPx2 and TrxR1. However, cardamonin treatment did not result in elevated GPx or TrxR activity and protein levels, possibly relating to a concomitant down-regulation of O-phosphoseryl-tRNA(Sec) kinase (PSTK), an enzyme involved in translation of selenoprotein mRNAs. On the other hand, induction of the Nrf2-regulated enzyme heme oxygenase 1 (HO-1) by cardamonin was diminished in Se-replete compared to Se-deficient cells. Our findings suggest that cardamonin interferes with the biosynthesis of Nrf2-regulated selenoenzymes, in contrast to the Nrf2-activating isothiocyanate compound sulforaphane, which has been shown earlier to synergize with Se-mediated cytoprotection. Conversely, the cellular Se status apparently affects the cardamonin-mediated induction of non-selenoprotein antioxidant enzymes such as HO-1. Copyright © 2015 Elsevier Inc. All rights reserved.

Synthesis, XRD crystal structure, spectroscopic characterization (FT-IR, 1H and 13C NMR), DFT studies, chemical reactivity and bond dissociation energy studies using molecular dynamics simulations and evaluation of antimicrobial and antioxidant activities of a novel chalcone derivative, (E)-1-(4-bromophenyl)-3-(4-iodophenyl)prop-2-en-1-one

NASA Astrophysics Data System (ADS)

Zainuri, D. Alwani; Arshad, Suhana; Khalib, N. Che; Razak, I. Abdul; Pillai, Renjith Raveendran; Sulaiman, S. Fariza; Hashim, N. Shafiqah; Ooi, K. Leong; Armaković, Stevan; Armaković, Sanja J.; Panicker, C. Yohannan; Van Alsenoy, C.

2017-01-01

In the present study, the title compound named as (E)-1-(4-bromophenyl)-3-(4-iodophenyl)prop-2-en-1-one was synthesized and structurally characterized by single-crystal X-ray diffraction. The compound crystallizes in the monoclinic system with P21/c space group with the unit cell parameters of a = 16.147 (2) Å, b = 14.270 (2) Å, c = 5.9058 (9) Å, β = 92.577 (3)° and Z = 4. The molecular geometry obtained from X-Ray structure determination was optimized by Density Functional Theory (DFT) using B3LYP/6-31G+(d, p)/Lanl2dz(f) method in the ground state. The IR spectrum was recorded and interpreted in details with the aid of Density Functional Theory (DFT) calculations and Potential Energy Distribution (PED) analysis. In order to investigate local reactivity properties of the title molecule, we have conducted DFT calculations of average local ionization energy surface and Fukui functions which were mapped to the electron density surface. In order to predict the open air stability and possible degradation properties, within DFT approach, we have also calculated bond dissociation energies. 1H and 13C NMR spectra were recorded and chemical shifts were calculated theoretically and compared with the experimental values. In addition, in vitro antimicrobial results show that the title compound has great potential of antibacterial activity against Staphylococcus aureus, Staphylococcus epidermidis and Micrococcus luteus bacteria and antifungal activity against Candida albicans in comparison to some reported chalcone derivatives. Antioxidant studies revealed the highest metal chelating activity of this compound.

Asymmetric Michael Addition Mediated by Chiral Ionic Liquids.

PubMed

Suzuki, Yumiko

2018-06-01

Chiral ionic liquids with a focus on their applications in asymmetric Michael additions and related reactions were reviewed. The examples were classified on the basis of the mode of asymmetric induction (e.g., external induction/non-covalent interaction or internal induction/covalent bond formation), the roles in reactions (as a solvent or catalyst), and their structural features (e.g., imidazolium-based chiral cations, other chiral oniums; proline derivatives). Most of the reactions with high chiral induction are Michael addition of ketones or aldehydes to chalcones or nitrostyrenes where proline-derived chiral ionic liquids catalyze the reaction through enamine/ iminium formation. Many reports demonstrate the recyclability of ionic liquid-tagged pyrrolidines.

Cytotoxic chalcones and flavonoids from the leaves of Muntingia calabura.

PubMed

Chen, Jih-Jung; Lee, Hsinn-Hsing; Duh, Chang-Yih; Chen, Ih-Sheng

2005-10-01

Two new dihydrochalcones, 2',4'-dihydroxy-3'-methoxydihydrochalcone, (-)-3'-methoxy-2',4',beta-trihydroxydihydrochalcone, a new flavanone, (2 S)-(-)-5'-hydroxy-7,3',4'-trimethoxyflavanone, and a new flavonol derivative, muntingone, along with sixteen known compounds, were isolated from the leaves of Muntingia calabura. The structures of these new compounds were determined using spectral analyses including extensive 2D NMR data. Among the isolates, (2 S)-5'-hydroxy-7,3',4'-trimethoxyflavanone, 4'-hydroxy-7-methoxyflavanone, 2',4'-dihydroxychalcone, and 2',4'-dihydroxy-3'-methoxychalcone exhibited cytotoxicity (IC (50) values < 4 microg/mL) against P-388 and/or HT-29 cell lines in vitro.

Surface and catalytic properties of acid metal carbons prepared by the sol gel method

NASA Astrophysics Data System (ADS)

Aguado-Serrano, J.; Rojas-Cervantes, M. L.; Martín-Aranda, R. M.; López-Peinado, A. J.; Gómez-Serrano, V.

2006-06-01

The sol-gel method has been applied for the synthesis of a series of acid metal-carbon xerogels (with M = V, Cr, Mo and Ni) by polymerisation of resorcinol with formaldehyde in the presence of metallic precursors. A blank sample was also prepared without any metal addition. The xerogels were heated in nitrogen at 1000 °C to obtain the pyrolysed products. The samples were characterised by different techniques such as thermal-mass spectrometry analysis, gas physisorption, and mercury porosimetry. In addition, the acid character of the pyrolysed products was tested by the Claisen-Schmidt condensation between benzaldehyde and acetophenone for the formation of chalcones.

Synthesis, biological activity and dyeing performance of some novel azo disperse dyes incorporating pyrazolo[1,5-a]pyrimidines for dyeing of polyester fabrics

NASA Astrophysics Data System (ADS)

Sayed, Ahmed Z.; Aboul-Fetouh, Mahmoud S.; Nassar, Hesham S.

2012-02-01

Several novel pyrazolopyrimidine azo compounds were achieved from diazotization of 4-aminoacetanilide and coupling with malononitrile and then refluxed with hydrazine hydrate to furnish 3,5-diamino-4-(4-acetamidophenylazo)-1H-pyrazole. The later compound was diazotized and coupled with substituted α-cyanocinnamate, α-cyanocinnamonitrile, 2-cyano-3-ethoxyacrylic acid ethyl ester, chalcones and ethylacetoacetate to produce novel dyestuffs. Structures of the dyes were fully characterized by using FT-IR, 1H NMR, mass spectroscopy and elemental analysis. The dyes were applied to polyester fiber, affording satisfactory results and showed biological activity towards various microorganisms.

Synthesis of 1-phenyl-3-(4'-nitrophenyl)-5-(3',4'-dimethoxy-6'-nitrophenyl)-2-pyrazoline and its antibacterial activity

NASA Astrophysics Data System (ADS)

Fauzi'ah, Lina; Wahyuningsih, Tutik Dwi

2017-03-01

Synthesis of pyrazoline substituted with nitro groups as antibacterial agent has been carried out by cycloaddition reaction. The compound was synthesized from chalcone and phenylhyrazine by refluxing them in 2-butanol for 24 h. The product was purified and characterized using FTIR and 1H-NMR spectrometers. The result showed that pyrazoline has been succesfully synthesized in 33.06% yield. The compund has antibacterial activity againts Bacillus subtilis and Shigella flexneri. However, it has tendency of activity for Gram-negative bacteria. In conclusion, the nitro groups that substituted in aromatic ring were predicted as a part of pharmacophore.

Discovery of gemfibrozil analogues that activate PPARα and enhance the expression of gene CPT1A involved in fatty acids catabolism.

PubMed

De Filippis, Barbara; Giancristofaro, Antonella; Ammazzalorso, Alessandra; D'Angelo, Alessandra; Fantacuzzi, Marialuigia; Giampietro, Letizia; Maccallini, Cristina; Petruzzelli, Michele; Amoroso, Rosa

2011-10-01

A new series of gemfibrozil analogues conjugated with α-asarone, trans-stilbene, chalcone, and their bioisosteric modifications were synthesized and evaluated to develop PPARα agonists. In this attempt, we have removed the methyls on the phenyl ring of gemfibrozil and introduced the above scaffolds in para position synthesizing two series of derivatives, keeping the dimethylpentanoic skeleton of gemfibrozil unaltered or demethylated. Four compounds exhibited good activation of the PPARα receptor and were also screened for their activity on PPARα-regulated gene CPT1A. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Growth and structure of a new photonic crystal: Chlorine substituted chalcone

NASA Astrophysics Data System (ADS)

Sarveshwara, H. P.; Raghavendra, S.; A, Jayarama; Menezes, Anthoni Praveen; Dharmaprakash, S. M.

2015-06-01

A new organic photonic material 3-(2, 4-dichlorophenyl)-1-(2,5-dimethylthiophen-3-yl)propan-1-one(DMTP) has been synthesized and crystallised in acetone solution. The functional groups present in the new material were identified by FTIR spectroscopy. The material is optically transparent in the wavelength range of 400-1100 nm. The crystal structure of DMTP was determined by single crystal X-ray diffraction. The title compound crystallizes in monoclinic system with a centrosymmetric space group P21/c. The Z-scan study revealed that the optical limiting property exhibited by the DMTP molecule is based on the reverse saturable absorption phenomena.

First X-ray crystal structure and internal reference diffusion-ordered NMR spectroscopy study of the prototypical Posner reagent, MeCu(SPh)Li(THF)3.

PubMed

Bertz, Steven H; Hardin, Richard A; Heavey, Thomas J; Jones, Daniel S; Monroe, T Blake; Murphy, Michael D; Ogle, Craig A; Whaley, Tara N

2013-07-29

Grow slow: The usual direct treatment of MeLi and CuSPh did not yield X-ray quality crystals of MeCu(SPh)Li. An indirect method starting from Me2CuLi⋅LiSPh and chalcone afforded the desired crystals by the slow reaction of the intermediate π-complex (see scheme). This strategy produced the first X-ray crystal structure of a Posner cuprate. A complementary NMR study showed that the contact ion pair was also the main species in solution. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.