Novel coumarins and related copper complexes with biological activity: DNA binding, molecular docking and in vitro antiproliferative activity.

PubMed

Pivetta, Tiziana; Valletta, Elisa; Ferino, Giulio; Isaia, Francesco; Pani, Alessandra; Vascellari, Sarah; Castellano, Carlo; Demartin, Francesco; Cabiddu, Maria Grazia; Cadoni, Enzo

2017-12-01

Coumarins show biological activity and are widely exploited for their therapeutic effects. Although a great number of coumarins substituted by heterocyclic moieties have been prepared, few studies have been carried out on coumarins containing pyridine heterocycle, which is known to modulate their physiological activities. We prepared and characterized three novel 3-(pyridin-2-yl)coumarins and their corresponding copper(II) complexes. We extended our investigations also to three known similar coumarins, since no data about their biochemical activity was previously been reported. The antiproliferative activity of the studied compounds was tested against human derived tumor cell lines and one human normal cell line. The DNA binding constants were determined and docking studies with DNA carried out. Selected Quantitative Structure-Activity Relationship (QSAR) descriptors were calculated in order to relate a set of structural and topological descriptors of the studied compounds to their DNA interaction and cytotoxic activity. Copyright © 2017 Elsevier Inc. All rights reserved.

Solvatochromic benzo[h] coumarins: Synthesis, solvatochromism, NLO and DFT study

NASA Astrophysics Data System (ADS)

Warde, Umesh; Sekar, Nagaiyan

2017-10-01

Three benzo[h] coumarins were synthesized and analyzed for their potential NLOphoric properties. Coumarins were synthesized using Knoevenagel condensation method by reacting hydroxyl-naphthalene aldehyde with cyano-methylelene-benzazoles containing NH, O and S elements respectively as the active methylene compounds. The absorption maxima for the coumarins are not affected by the solvent polarity but emission maxima does. Emission solvatochromism was analyzed using various solvent polarity functions which highlights the polarity dependency of the emission profile. Coumarins showed satisfactory values for first and second hyperpolarizability which are comparable using solvatochromism and DFT. NLO properties are also compared with the limits of hyperpolarizability calculated using sum rule of quantum mechanics. Results show that the NLO properties predicted by DFT are close to the upper limits of hyperpolarizability. The functional CAM-B3LYP is proven to be suitable for predicting NLO properties for these coumarins compared to functional B3LYP. The present study highlights the importance of such molecules for incorporating in advanced NLOphores.

A comparison of US and Norwegian regulation of coumarin in tobacco products

PubMed Central

Givel, M

2003-01-01

Objective: This paper examines policy processes regarding why the USA and Norway have not regulated coumarin in tobacco. Design: A qualitative analysis of all tobacco industry documents regarding coumarin since the 1950s from the 1998 US Master Settlement Agreement and subsequent legal settlements. Additional data were collected from newspaper reports, general internet search engines, journal articles, scholarly reports, court cases, statutes, regulations, and informal correspondence with tobacco control experts in Norway. Main outcome measure: An overview, summary, and analysis of all documents related to coumarin. Results: In the USA from 1954 until 1985 when coumarin was reportedly removed from domestic cigarettes, but not from pipe tobacco until 1996, and not at all from imported Indian bidi cigarettes, regulatory efforts were stymied. In Norway, from 1973 to the present, the tobacco industry has never disclosed whether its tobacco products contain coumarin. In both the USA and Norway, the extreme delay and lack of vigorous evidence gathering and significant remedies were caused by tobacco industry assertions that revealing tobacco additives was a violation of trade secrets, and by weak regulatory authority and efforts to regulate coumarin. Conclusion: Vigorous and expeditious regulatory investigations and remedies for harmful additives in tobacco, such as coumarin, can protect the public health. Astute insider and outsider political advocacy by health advocates is required to hold elected officials and civil servants publicly accountable for failing to enact disclosure laws and to engage in effective regulatory efforts. PMID:14660776

Effect of coumarins on HL-60 cell differentiation.

PubMed

Kawaii, S; Tomono, Y; Katase, E; Ogawa, K; Yano, M

2000-01-01

Twenty-eight coumarins, including 7 furocoumarins, were examined for their activity of induction of terminal differentiation of human promyelocytic leukemia cells (HL-60) by nitro blue tetrazolium (NBT) reducing, nonspecific esterase, specific esterase and phagocytic activities. Esculetin, nordalbergin, 6,7-dihydroxy-4-methylcoumarin and imperatorin had strong activity among the coumarins examined. HL-60 cells treated with these coumarins differentiated into mature monocyte/macrophage. The structure-activity relationship established from the results revealed that 6,7-dihydroxy moiety had an important role in the induction of differentiation of HL-60.

New coumarin carboxylates having trifluoromethyl, diethylamino and morpholino terminal groups: Synthesis and mesomorphic characterisations

NASA Astrophysics Data System (ADS)

Srinivasa, Hosapalya Thimmaiah; Harishkumar, Hosanagara Narayana; Palakshamurthy, Bandrehalli Siddagangappa

2017-03-01

New set of trifluromethyl, diethylamino and morpholino derived coumarin compounds were prepared by reacting various coumarin 3-carboxylic acids with various phenyl esters with peripheral alkyl, ester and polar cyano moieties in the presence of EDC.HCl/DMAP as esterification agent. The chemical structures of new coumarin derivatives were confirmed by standard spectroscopic techniques and mesomorphic behaviours were established by polarised optical microscopy (POM) and differential scanning calorimetry (DSC). Trifluoromethane and morpholino derivatives show SmA/Nematic phase, while diethylamino derivatives did not show liquid crystalline property.

13C CP MAS NMR and GIAO-CHF calculations of coumarins.

PubMed

Zolek, Teresa; Paradowska, Katarzyna; Wawer, Iwona

2003-01-01

13C cross-polarization magic-angle spinning NMR spectra were recorded for a series of solid coumarins. Ab initio calculations of shielding constants were performed with the use of GIAO-CHF method. The combined CPMAS NMR and theoretical approach was successful in characterizing solid-state conformations of coumarins; a relationship sigma (ppm) = -1.032 xdelta + 205.28 (R(2) = 0.9845) can be used to obtain structural information for coumarins, for which solid-state NMR or crystal structure data are not available. Copyright 2002 Elsevier Science (USA)

Broadband Light-Harvesting Molecular Triads with High FRET Efficiency Based on the Coumarin-Rhodamine-BODIPY Platform.

PubMed

He, Longwei; Zhu, Sasa; Liu, Yong; Xie, Yinan; Xu, Qiuyan; Wei, Haipeng; Lin, Weiying

2015-08-17

Broadband capturing and FRET-based light-harvesting molecular triads, CRBs, based on the coumarin-rhodamine-BODIPY platform were rationally designed and synthesized. The absorption band of CRBs starts from blue-green to yellow-orange regions (330-610 nm), covering the strong radiation scope of sunlight. The peripheral coumarin and BODIPY chromophore energy could transfer to the central acceptor rhodamine by a one-step direct way. The energy of the coumarin moiety could also transfer to the BODIPY unit, subsequently transferring to the rhodamine core by two-step sequential ways. Both the efficiencies of the coumarin moiety and the BODIPY unit to the rhodamine core in CRBs, determined by two different ways, are very high. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

21 CFR 189.130 - Coumarin.

Code of Federal Regulations, 2012 CFR

2012-04-01

... detecting coumarin in food are in sections 19.016-19.024 of the “Official Methods of Analysis of the... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Coumarin. 189.130 Section 189.130 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN...

21 CFR 189.130 - Coumarin.

Code of Federal Regulations, 2013 CFR

2013-04-01

... detecting coumarin in food are in sections 19.016-19.024 of the “Official Methods of Analysis of the... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Coumarin. 189.130 Section 189.130 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN...

21 CFR 189.130 - Coumarin.

Code of Federal Regulations, 2010 CFR

2010-04-01

... detecting coumarin in food are in sections 19.016-19.024 of the “Official Methods of Analysis of the... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Coumarin. 189.130 Section 189.130 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN...

Novel push-pull fluorescent dyes - 7-(diethylamino)furo- and thieno[3,2-c]coumarins derivatives: structure, electronic spectra and TD-DFT study

NASA Astrophysics Data System (ADS)

Akchurin, Igor O.; Yakhutina, Anna I.; Bochkov, Andrei Y.; Solovjova, Natalya P.; Medvedev, Michael G.; Traven, Valerii F.

2018-05-01

Novel push-pull fluorescent dyes - 7-(diethylamino)furo- and 7-(diethylamino)thieno[3,2-c]coumarins derivatives have been synthesized using formyl derivatives of furo- and thieno[3,2-c]coumarins as starting materials. Electron absorption and fluorescent spectra of the dyes have been recorded in different solvents. Structure and solvent effects on the dyes spectral characteristics were analyzed. The fusion of five-membered heterocycle to coumarin provides a definite increase of Stokes shifts in all solvents and results in higher quantum yields of fluorescence. The absorption and emission bands of thieno[3,2-c] coumarin derivatives are definitely shifted to the red region (3-30 nm) compared to similar derivatives of furo[3,2-c]coumarin. TD-DFT calculations of some of the studied compounds have shown that hybrid DFT functionals and adequate representation of molecular environment are essential for obtaining accurate UV-Vis absorption spectra for the dyes with extended π-system. The longest-wave electron transitions in the studied compounds were computationally shown to be of push-pull nature.

Effect of solvent polarity levels on separation of xanthone and coumarin from Calophyllum inophyllum leaves extract

NASA Astrophysics Data System (ADS)

Susanto, D. F.; Hapsari, S.; Trilutfiani, Z.; Borhet, A.; Aparamarta, H. W.; Widjaja, A.; Gunawan, S.

2018-03-01

Calophyllum inophyllum has various benefits that can be utilized from root, stem, leaf, until seed. C. inophyllum leaves contain many bioactive compounds, such as xanthone and coumarin which are useful as antioxidant, and inhibitors of enzyme activity from HIV virus. The aim of this research was to investigate the effect of solvent polarity levels on the separation of xanthone and coumarin compounds contained in the crude extract of C. inophyllum leaves. Crude leaves extract was obtained by percolation method. Moreover, Liquid Liquid Extraction (LLE) was used for separating xanthone and coumarin compounds. It was performed by methanol (polar solvent) and hexane (non-polar solvent) with solvent ratio of 1. Methanol concentration in water used were 20%, 50%, 80%, and 100%. Each fraction obtained was tested qualitatively using Thin Layer Chromatography (TLC) and quantitatively using Gas Chromatography (GC) to analyze xanthone and coumarin. The best separation result was obtained by using 50% methanol. In this results, coumarin and xanthones were separated in methanol fraction (81.18% recovery) and in hexane fraction (81.91% recovery), respectively.

Tagging RDT&E Volume 2--Appendices A-G

DTIC Science & Technology

1994-03-01

significantly from the index matched case. C - 20 S• nj= 1.4 0 a nj= 1.5 o nj= 1.6 C • ni= 1.64 10 S15 *% 0 -0.0 0.5 1.0 1.5 2.0 Fiber-Dump Separation...index matching fluid, dump fiber characteristics, laser fluence, and laser wavelength. C -30 * Coumarin 460 o Coumarin 500 * Rhodamine 590a A Kiton Red...Splice • IE-5 o Coumarin 460 * Coumarin 500 T Rhodamine 590 A Kitton Red 620 * DCM 0 LDS 698 OEO0 450 500 550 600 650 700 Wavelength (rim) Figure C -21

Solvatochromic studies on 4-Bromomethyl-7-methyl coumarins

NASA Astrophysics Data System (ADS)

Khanapurmath, Netravati; Kulkarni, Manohar V.; Pallavi, L.; Yenagi, Jayashree; Tonannavar, Jagdish

2018-05-01

Non- and dinitro 4-bromomethyl-7-methyl coumarins and new mono- and trinitro 4-bromomethyl-7-methyl coumarins have been synthesized. Effect of nitro groups on the photophysical properties of the parent 4-bromomethyl-7-methyl coumarin has been reported. Their ground and excited state dipole moments have been estimated by solvatochromic method using nine solvents. A reasonable agreement has been observed between calculated and observed dipole moments. Reduction in dipole moment has been observed for mono- and dinitro compounds where as the trinitro compound was found to have higher dipole moment in the excited state.

[Simultaneous analysis of aromatic aldehydes and coumarins with high pressure liquid chromatography. Application to wines and brandies stored in oak barrels].

PubMed

Salagoity-Auguste, M H; Tricard, C; Sudraud, P

1987-04-17

Aromatic aldehydes (vanillin, syringaldehyde, coniferaldehyde and sinapaldehyde) and coumarins (esculetin, umbelliferone, scopoletin and methylumbelliferone) are natural wood compounds. Storage of wines and brandies in oak barrels increases notably aldehydes and coumarins (particularly scopoletin) concentrations. These compounds were separated by high-performance liquid chromatography, on hydrocarbon bonded reversed-phase packings, with a water-acetonitrile elution gradient. They were first extracted from wines and brandies by diethyl ether and then injected on chromatographic column. A double detection was used to determine simultaneously aromatic aldehydes and coumarins by UV absorption and fluorescence respectively.

Pharmacological and Nutritional Effects of Natural Coumarins and Their Structure-Activity Relationships.

PubMed

Zhu, Jing-Jing; Jiang, Jian-Guo

2018-05-11

Coumarins are fused benzene and pyrone ring systems with a wide spectrum of bioactivities including anti-tumor, anti-inflammation, antiviral and antibacterial effects. In this paper, the current development of coumarins-based drugs is introduced, and their structure-activity relationship is discussed by reviewing the relevant literatures published in the past twenty years. Coumarin molecules can be customized by the target site to prevent systemic side effects by virtue of structural modification. The ortho-phenolic hydroxyl on the benzene ring had remarkable antioxidant and anti-tumor activities. Coumarins with aryl groups at the C-4 position have good activities in anti-HIV, anti-tumor, anti-inflammation and analgesia. C-3 phenylcoumarins have strong anti-HIV and antioxidant effects. Tetracycline pyranocoumarins can significantly inhibit the HIV, osthol structural analogues have antimicrobial activity. Praeruptorin C and its derivatives play an important role in lowering blood pressure and dilating coronary arteries, and khellactone derivatives have significant inhibitory effects on AIDS, cancer and cardiovascular diseases. It is concluded that the specific site on the core structure of coumarin exhibits one or more activities due to the electronic or steric effects of the substituents. This review is designed to be conducive to rational design and development of more active and less toxic agents with a coumarin scaffold. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

PEG-coumarin based biocompatible self-assembled fluorescent nanoaggregates synthesized via click reactions and studies of aggregation behavior.

PubMed

Behl, Gautam; Sikka, Manisha; Chhikara, Aruna; Chopra, Madhu

2014-02-15

Click chemistry has found wide application in drug discovery, bioconjugation reactions, polymer chemistry and synthesis of amphiphilic materials with pharmaceutical and biomedical applications. Triazole substitution via a click reaction alters photophysical properties of coumarin. Both coumarin and triazole moieties participate in π-π stacking interactions. Hence it should be possible to prepare fluorescent self-assembly systems by conjugation of coumarin to poly (ethylene glycol) (PEG) via click reactions exhibiting hydrophilic, hydrophobic and π-π stacking interactions. Moreover, the materials can be suitable platforms to assess fluorescence modulation effect of triazole substitution on coumarins. PEG supported coumarin conjugates were synthesized and the fluorescence modulation effect of the formation of triazole on coumarin was assessed. Their aggregation properties were studied by surface tension measurements, dynamic light scattering (DLS), transmission electron microscopy (TEM), fluorescence and (1)H NMR spectroscopy. The conjugates were found to form nanoaggregates in the size range of 100-120 nm with a negative free energy of micellization (~-27 kJ mol(-1)) confirming aggregation and self-assembly. The Quantum yield of 4-methyl-7-propargylcoumarin (7P4MC) was enhanced after triazole formation with azide functionalized PEG (methoxy-PEG350 azide). The conjugates were found to exhibit π-π stacking interactions in addition to hydrophilic and hydrophobic interactions. They were found to be biocompatible with human pancreatic cancer cells. Copyright © 2013 Elsevier Inc. All rights reserved.

Early and late effects of coumarin therapy started before percutaneous coronary intervention: Clinical, angiographic and cost-effective outcome of the Balloon Angioplasty and Anticoagulation Study (BAAS).

PubMed

Ten Berg, J M; Kelder, J C; Suttorp, M J; Mast, E G; Bal, E T; Ernst, J M P G; Plokker, H W M

2002-05-01

Coronary angioplasty frequently creates a thrombogenic surface with subsequent mural thrombosis that may lead to acute complications and possibly stimulates the development of restenosis. Whether coumarins can prevent these complications is unclear. In the Balloon Angioplasty and Anticoagulation Study (BAAS), the effect of coumarins started before the procedure on early and late outcome was studied. Patients were randomised to aspirin only or to aspirin plus coumarins. Half of the patients were randomised to undergo six-month angiographic follow-up. Study medication was started one week before coronary angioplasty and the target international normalised ratio (INR) was 2.1-4.8 during angioplasty and six-month follow-up. 'Optimal' anticoagulation was defined as an INR in the target range for at least 70% of the follow-up time. In addition, cost-effectiveness of coumarin treatment was measured. At one year death, myocardial infarction, target-lesion revascularisation and stroke were observed in 14.3% of the 530 patients randomised to aspirin plus coumarin versus in 20.3% of the 528 patients randomised to aspirin alone (relative risk 0.71; 95% CI 0.54-0.93). The incidence of major bleedings and false aneurysms during hospitalisation was 3.2% and 1.0%, respectively, (relative risk 3.39; 95% CI 1.26-9.11). Optimal anticoagulation was an independent predictor of late thrombotic events (relative risk, 0.33; 95% CI, 0.19-0.57). Quantitative coronary analysis was performed of 301 lesions in the ASA group and of 297 lesions in the coumarin group. At six months, the minimal luminal diameter was similar in the ASA and coumarin group. However, optimal anticoagulation was an independent predictor of angiographic outcome at six months. Optimal anticoagulation led to a 0.21 mm (95% CI: 0.05-0.37) larger MLD as compared with suboptimal anticoagulation whereas aspirin use led to a 0.12 mm (95% CI -0.28-0.04) smaller MLD. When including all costs, the savings associated with coumarin treatment were estimated at € 235 per patient after one year. Coumarin pretreatment reduces early and late events in patients undergoing percutaneous coronary intervention at the expense of a small increase in nonfatal bleeding complications. Furthermore, an optimal level of anticoagulation is associated with a significantly better outcome as compared with a suboptimal level of anticoagulation. In addition, coumarin treatment reduces costs.

Ratiometric fluorescence sensing of mercuric ion based on dye-doped lanthanide coordination polymer particles.

PubMed

Zhang, Zhenzhen; Wu, Yongmei; He, Shizhen; Xu, Yuanyuan; Li, Gaiping; Ye, Baoxian

2018-07-19

This work focused on the development of a novel ratiometric fluorescence sensor for detection of Hg 2+ by using dye-doped lanthanide infinite coordination polymer (Ln-ICP) particles. The dye-doped Ln-ICP used herein was prepared by self-assemble of adenosine monophosphate (AMP) with Ce 3+ and Tb 3+ (Ce/Tb-AMP) through self-adaptive chemistry, in which the fluorescent dye coumarin was encapsulated during the assembly process as a guest molecule. Under 310 nm irradiation, the obtained coumarin@Ce/Tb-AMP itself emitted characteristic green luminescence of Tb 3+ , accompanied with a weak fluorescence at 445 nm originated from coumarin encapsulated in the Ce/Tb-AMP networks. The fluorescence emission of coumarin became strong when it was released to the solution. In the presence of Hg 2+ , the coumarin@Ce/Tb-AMP was destroyed due to the specific coordination interaction between AMP and Hg 2+ , which leaded to the release of coumarin to the solution meanwhile. Consequently, the fluorescence of Ce/Tb-AMP was quenched, while that of coumarin enhanced. On the basis of this strategy, we developed a novel ratiometric fluorescent sensor for the detection of Hg 2+ by measuring the ratio of fluorescent intensity of the coumarin@Ce/Tb-AMP suspension, which showed a wide linear range from 0.08 to 1000 nM and detection limit of 0.03 nM with high selectivity and sensitivity. Furthermore, the constructed ratiometric fluorescent sensor was successfully applied in detecting Hg 2+ in drinking water and human blood serum (HBS) with satisfactory results. Copyright © 2018 Elsevier B.V. All rights reserved.

Photochemical synthesis and photophysical properties of coumarins bearing extended polyaromatic rings studied by emission and transient absorption measurements.

PubMed

Yamaji, Minoru; Hakoda, Yuma; Okamoto, Hideki; Tani, Fumito

2017-04-12

We prepared a variety of coumarin derivatives having expanded π-electron systems along the direction crossing the C 3 -C 4 bond of the coumarin skeleton via a photochemical cyclization process and investigated their photophysical features as a function of the number (n) of the added benzene rings based on emission and transient absorption measurements. Upon increasing n, the fluorescence quantum yields of the π-extended coumarins increased. Expanding the π-electron system on the C 3 -C 4 bond of the coumarin skeleton was found to be efficient for increasing the fluorescence ability more than that on the C 7 -C 8 bond. Introducing the methoxy group at the 7-position was also efficient for enhancing the fluorescence quantum yield and rate of the expanded coumarins. The non-radiative process from the fluorescence state was not substantially influenced by the expanded π-electron system. The competitive process with the fluorescence was found to be intersystem crossing to the triplet state based on the observations of the triplet-triplet absorption. The effects of the expanded π-electron systems on the fluorescence ability were investigated with the aid of TD-DFT calculations.

Chirality transfer effects in proline-substituted coumarin compounds.

PubMed

Park, Eun-Kyung; Park, Bongjeong; Choi, Jun-Ho; Choi, Kihang; Cho, Minhaeng

2009-08-13

Conformations of proline-substituted chromophores are determined by using circular dichroism (CD) spectroscopy and quantum chemistry calculation method. Coumarin is chosen for the optical chromophore and proline amino acid is attached to its C7 position. The coumarin-proline conjugate considered contains both fluorophore and peptide linker where any polypeptides or biomolecules can be additionally connected to the free carboxyl group of the proline. Thus, the coumarin-proline is a potentially useful composite chirality-probe system for studies of protein dynamics in solution. However, detailed conformation of coumarin ring with respect to the proline ring has to be determined first. We found that there are two possible conformers, which differ from each other by the relative orientation of the coumarin ring. Comparing the measured CD spectra with the calculated ones, we directly show that only one of the two conformers is dominant in polar solvents except for water. The present study suggests that the local structure around an optical chromophore, when it is introduced to polypeptides or other biomolecules, can be studied by examining the electronic optical activity of the probe chromophore, as long as the chirality transfer from the attached amino acid to the chromophore is significantly large.

A Method for LC-MS/MS Profiling of Coumarins in Zanthoxylum zanthoxyloides (Lam.) B. Zepernich and Timler Extracts and Essential Oils.

PubMed

Tine, Yoro; Renucci, Franck; Costa, Jean; Wélé, Alassane; Paolini, Julien

2017-01-22

The metabolites from the coumarin class, present in tissues of plants belonging mainly to the Rutaceae and Apiaceae families, included compounds with high chemical diversity such as simple coumarins and furocoumarins. These health-promoting components are recognized for their valuable biological activities in herbal preparations but also for their phototoxic effects. In this work, a targeted liquid chromatography (LC) coupled with tandem mass spectrometry (MS²) was developed for the screening of 39 reference standards of coumarins and furocoumarins in essential oils and plant extracts. Chromatographic separation was accomplished on reversed phase column using water/acetonitrile as the mobile phase and detection was performed on a hybrid QqQ/linear ion trap spectrometer fitted with an atmospheric pressure chemical ionization (APCI) source operating in positive ion mode. This analytical approach was applied to investigate the coumarin compositions of fruit essential oils and methanolic extracts obtained from separated parts (fruit, leaf, stem, trunk, and root) of Zanthoxylum zanthoxyloides . Ten coumarins and six furanocoumarins were reported in this species and data analyses were used to assess the suitability of these compounds to the metabolomics-based differentiation of plant organs. The quantification criteria of the metabolites in extract samples included linearity, limit of quantification, limit of detection, and matrix effect were validated. As reported for other species of the Rutaceae family, the concentration of coumarins was drastically higher in Z. zanthoxyloides fruits than in other plant organs.

Comparative evaluation of flavone from Mucuna pruriens and coumarin from Ionidium suffruticosum for hypolipidemic activity in rats fed with high fat diet.

PubMed

Dharmarajan, Satheesh Kumar; Arumugam, Kottai Muthu

2012-10-02

The objective of the study is a comparative evaluation of flavone isolated from Mucuna pruriens and coumarin isolated from Ionidium suffruticosum was assessed for the hypolipidemic activity in rats fed with high fat diet. The acute toxicity study was found that flavone (M.pruriens) and coumarin (I.suffruticosum) are safe up to 100 mg/kg, so one tenth of this dose (10 mg/kg) was consider as a evaluation dose. High fat diet group of rats showed significant (p<0.001) elevation in plasma total and LDL-cholesterol, triglycerides and phospholipids. Administration of flavone (M. pruriens) and coumarin isolated from (I.suffruticosum) at the dose of 10mg/kg b.wt/day along with high fat diet significantly (p<0.001) prevented the rise in the plasma total and LDL-cholesterol, triglycerides and phospholipids than that of other extracts. However, treatment of coumarin isolated from (I.suffruticosum) had showed more cardio protective effect against hyperlipidemia than that of flavone (M.pruriens).

Esculetin and esculin (esculetin 6-O-glucoside) occur as inclusions and are differentially distributed in the vacuole of palisade cells in Fraxinus ornus leaves: a fluorescence microscopy analysis.

PubMed

Tattini, Massimiliano; Di Ferdinando, Martina; Brunetti, Cecilia; Goti, Andrea; Pollastri, Susanna; Bellasio, Chandra; Giordano, Cristiana; Fini, Alessio; Agati, Giovanni

2014-11-01

The location of individual coumarins in leaves of Fraxinus ornus acclimated at full solar irradiance was estimated using their specific UV- and fluorescence spectral features. Using a combination of UV-induced fluorescence and blue light-induced fluorescence of tissues stained with diphenylborinic acid 2-amino-ethylester, in wide field or confocal laser scanning microscopy, we were able to visualize the distribution of esculetin and esculetin 6-O-glucoside (esculin) in palisade cells. Coumarins are not uniformly distributed in the cell vacuole, but accumulate mostly in the adaxial portion of palisade cells. Our study indeed shows, for the first time, that coumarins in palisade cells accumulate as vacuolar inclusions, as previously reported in the pertinent literature only for anthocyanins. Furthermore, esculetin and esculin have a different vacuolar distribution: esculetin largely predominates in the first 15 μm from the adaxial epidermis. This leads to hypothesize for esculetin and esculin different transport mechanisms from the endoplasmic reticulum to the vacuole as well as potentially different roles in photoprotection. Our study open to new experiments aimed at exploring the mechanisms that deliver coumarins to the vacuole using different fluorescence signatures of coumarin aglycones and coumarin glycosides. Copyright © 2014 Elsevier B.V. All rights reserved.

Determination of coumarin in seasonal bakery products using QuEChERS and GC-MS.

PubMed

Vetter, F; Müller, C; Stöckelhuber, M; Bracher, F

2017-06-01

Cinnamon is a traditional herbal drug, but more importantly, it is used as a flavor compound in the production of foodstuff. Due to the content of significant concentrations of coumarin in Cassia cinnamon, effective control of the coumarin content in seasonal bakery products like ginger bread and cinnamon biscuits is urgently needed. Here we present a novel, fast and fully validated protocol for the determination of coumarin in marketed bakery products using the QuEChERS sample preparation technique in combination with GC-MS analysis. Ten grams of homogenized sample was mixed with 20 mL acetonitrile/water (1:1) and 5 g magnesium sulfate/sodium chloride mixture (4:1). The organic phase was cleaned by dSPE with 25 mg magnesium sulfate/PSA (5:1). The LOD was 0.15 μg/mL and the LOQ 0.50 μg/mL. We detected a mean coumarin content of 19.5 μg/kg in 9 out of 14 seasonal food products (ranging from 1.45 to 39.4 mg/kg). No coumarin was detected in five cinnamon containing products. With this investigation we demonstrate that the QuEChERS sample preparation, previously applied mainly to the analysis of pesticides in vegetables, is also suitable for other complex matrices.

Ultrafast Electron Transfer across a Nanocapsular Wall: Coumarins as Donors, Viologen as Acceptor, and Octa Acid Capsule as the Mediator.

PubMed

Chuang, Chi-Hung; Porel, Mintu; Choudhury, Rajib; Burda, Clemens; Ramamurthy, V

2018-01-11

Results of our study on ultrafast electron transfer (eT) dynamics from coumarins (coumarin-1, coumarin-480, and coumarin-153) incarcerated within octa acid (OA) capsules as electron donors to methyl viologen dissolved in water as acceptor are presented. Upon photoexcitation, coumarin inside the OA capsule transfers an electron to the acceptor electrostatically attached to the capsule leading to a long-lived radical-ion pair separated by the OA capsular wall. This charge-separated state returns to the neutral ground state via back electron transfer on the nanosecond time scale. This system allows for ultrafast electron transfer processes through a molecular wall from the apolar capsular interior to the highly polar (aqueous) environment on the femtosecond time scale. Employing femtosecond transient absorption spectroscopy, distinct rates of both forward (1-25 ps) and backward eT (700-1200 ps) processes were measured. Further understanding of the energetics is provided using Rehm-Weller analysis for the investigated photoinduced eT reactions. The results provide the rates of the eT across a molecular wall, akin to an isotropic solution, depending on the standard free energy of the reaction. The insights from this work could be utilized in the future design of efficient electron transfer processes across interfaces separating apolar and polar environments.

The influence of naphthaleneacetic acid (NAA) and coumarin on flavonoid production by fungus Phellinus sp.: modeling of production kinetic profiles.

PubMed

Ma, Xiao-Kui; Li, Le; Peterson, Eric Charles; Ruan, Tingting; Duan, Xiaoyi

2015-11-01

For the purpose of improving the fungal production of flavonoids, the influence of naphthaleneacetic acid (NAA) and coumarin on flavonoid production by fungus Phellinus sp. P0988 was investigated by developing the corresponding kinetics of flavonoid production in a 7-L bioreactor. Phellinus sp. was confirmed to form flavonoids in pellets and broth when cultivated in basic medium, and the optimum concentration of NAA and coumarin in medium for flavonoid production were determined to be 0.03 and 0.02 g/L, respectively. The developed unstructured mathematical models were in good agreement with the experimental results with respect to flavonoid production kinetic profiles with NAA and coumarin supplementation at optimum levels and revealed significant accuracy in terms of statistical consistency and robustness. Analysis of these kinetic processes indicated that NAA and coumarin supplementations imposed a stronger positive influence on flavonoid production and substrate consumption compared to their effects on cell growth. The separate addition of NAA and coumarin resulted in enhancements in final product accumulation and productivity, achieving final flavonoid concentrations of 3.60 and 2.75 g/L, respectively, and glucose consumption showed a significant decrease compared to the non-supplemented control as well. Also, the separate presence of NAA and coumarin respectively decreased maintenance coefficients (M s) from 2.48 in the control to 1.39 and 0.22, representing decreases of 43.9 and 91.1 %, respectively. The current study is the first known application of mathematical kinetic models to explore the influence of medium components adding on flavonoid production by fungi.

The Distribution of Coumarins and Furanocoumarins in Citrus Species Closely Matches Citrus Phylogeny and Reflects the Organization of Biosynthetic Pathways

PubMed Central

Dugrand-Judek, Audray; Olry, Alexandre; Hehn, Alain; Costantino, Gilles; Ollitrault, Patrick; Froelicher, Yann; Bourgaud, Frédéric

2015-01-01

Citrus plants are able to produce defense compounds such as coumarins and furanocoumarins to cope with herbivorous insects and pathogens. In humans, these chemical compounds are strong photosensitizers and can interact with medications, leading to the “grapefruit juice effect”. Removing coumarins and furanocoumarins from food and cosmetics imply additional costs and might alter product quality. Thus, the selection of Citrus cultivars displaying low coumarin and furanocoumarin contents constitutes a valuable alternative. In this study, we performed ultra-performance liquid chromatography coupled with mass spectrometry analyses to determine the contents of these compounds within the peel and the pulp of 61 Citrus species representative of the genetic diversity all Citrus. Generally, Citrus peel contains larger diversity and higher concentrations of coumarin/furanocoumarin than the pulp of the same fruits. According to the chemotypes found in the peel, Citrus species can be separated into 4 groups that correspond to the 4 ancestral taxa (pummelos, mandarins, citrons and papedas) and extended with their respective secondary species descendants. Three of the 4 ancestral taxa (pummelos, citrons and papedas) synthesize high amounts of these compounds, whereas mandarins appear practically devoid of them. Additionally, all ancestral taxa and their hybrids are logically organized according to the coumarin and furanocoumarin pathways described in the literature. This organization allows hypotheses to be drawn regarding the biosynthetic origin of compounds for which the biogenesis remains unresolved. Determining coumarin and furanocoumarin contents is also helpful for hypothesizing the origin of Citrus species for which the phylogeny is presently not firmly established. Finally, this work also notes favorable hybridization schemes that will lead to low coumarin and furanocoumarin contents, and we propose to select mandarins and Ichang papeda as Citrus varieties for use in creating species devoid of these toxic compounds in future breeding programs. PMID:26558757

A highly sensitive and selective off-on fluorescent chemosensor for hydrazine based on coumarin β-diketone

NASA Astrophysics Data System (ADS)

Wu, Wei-Na; Wu, Hao; Wang, Yuan; Mao, Xian-Jie; Zhao, Xiao-Lei; Xu, Zhou-Qing; Fan, Yun-Chang; Xu, Zhi-Hong

2018-01-01

A coumarin-based sensor C1, namely 3-acetoacetylcoumarin was designed, synthesized and applied for hydrazine detection. Hydrazinolysis of the chemosensor gives a fluorescent coumarin-pyrazole product C1 - N2H4 [3-(3-methyl-1H-pyrazol-5-yl)coumarin], and thus resulting in a prominent fluorescence off-on response toward hydrazine under physiological conditions. The probe is highly selective toward hydrazine over cations, anions and other biologically/environmentally abundant analytes. The detection limit of the probe is 3.2 ppb. The sensing mechanism was supported by 1H NMR, IR, MS and DFT calculation. The application of the fluorescent probe in monitoring intracellular hydrazine in glioma cell line U251 was also demonstrated.

In vitro antifungal activity of coumarin extracted from Loeselia mexicana Brand.

PubMed

Navarro-García, Victor M; Rojas, Gabriela; Avilés, Margarita; Fuentes, Macrina; Zepeda, Gerardo

2011-09-01

The bis-coumarin daphnoretin and its monomeric precursors scopoletin and umbelliferone were isolated for the first time from the aerial part of Loeselia mexicana Brand (a vegetal species used in Mexican traditional medicine) using chromatographic techniques. The structures of these compounds were determined by (1) H and (13) C NMR analyses. These coumarins were evaluated for in vitro antifungal activity. The three compounds tested showed significant antifungal activity. © 2011 Blackwell Verlag GmbH.

Synthesis and characterization of mixed monolayer protected gold nanorods and their Raman activities

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

Mlambo, Mbuso; Nanotechnology Innovation Centre, Advanced Materials Division, Mintek, Private Bag X3015, Randburg 2125; Mdluli, Phumlani S.

2013-10-15

Graphical abstract: Gold nanorods surface functionalization. - Highlights: • Mixed monolayer protected gold nanorods. • Surface enhanced Raman spectroscopy. • HS-(CH{sub 2}){sub 11}-NHCO-coumarin as a Raman active compound. - Abstract: The cetyltrimethylammonium bromide (CTAB) gold nanorods (AuNRs) were prepared by seed-mediated route followed by the addition of a Raman active compound (HS-(CH{sub 2}){sub 11}-NHCO-coumarin) on the gold nanorods surfaces. Different stoichiometric mixtures of HS-(CH{sub 2}){sub 11}-NHCO-coumarin and HS-PEG-(CH{sub 2}){sub 11}COOH were evaluated for their Raman activities. The lowest stoichiometric ratio HS-(CH{sub 2}){sub 11}-NHCO-coumarin adsorbed on gold nanorods surface was detected and enhanced by Raman spectroscopy. The produced mixed monolayer protectedmore » gold nanorods were characterized by UV-vis spectrometer for optical properties, transmission electron microscope (TEM) for structural properties (shape and aspect ratio) and their zeta potentials (charges) were obtained from ZetaSizer to determine the stability of the produced mixed monolayer protected gold nanorods. The Raman results showed a surface enhanced Raman scattering (SERS) enhancement at the lowest stoichiometric ratio of 1% HS-(CH{sub 2}){sub 11}-NHCO-coumarin compared to high ratio of 50% HS-(CH{sub 2}){sub 11}-NHCO-coumarin on the surface of gold nanorods.« less

Comparative evaluation of flavone from Mucuna pruriens and coumarin from Ionidium suffruticosum for hypolipidemic activity in rats fed with high Fat diet

PubMed Central

2012-01-01

The objective of the study is a comparative evaluation of flavone isolated from Mucuna pruriens and coumarin isolated from Ionidium suffruticosum was assessed for the hypolipidemic activity in rats fed with high fat diet. The acute toxicity study was found that flavone (M.pruriens) and coumarin (I.suffruticosum) are safe up to 100mg/kg, so one tenth of this dose (10mg/kg) was consider as a evaluation dose. High fat diet group of rats showed significant (p<0.001) elevation in plasma total and LDL-cholesterol, triglycerides and phospholipids. Administration of flavone (M. pruriens) and coumarin isolated from (I.suffruticosum) at the dose of 10mg/kg b.wt/day along with high fat diet significantly (p<0.001) prevented the rise in the plasma total and LDL-cholesterol, triglycerides and phospholipids than that of other extracts. However, treatment of coumarin isolated from (I.suffruticosum) had showed more cardio protective effect against hyperlipidemia than that of flavone (M.pruriens). PMID:23031584

Coumarin benzothiazole derivatives as chemosensors for cyanide anions

NASA Astrophysics Data System (ADS)

Wang, Kangnan; Liu, Zhiqiang; Guan, Ruifang; Cao, Duxia; Chen, Hongyu; Shan, Yanyan; Wu, Qianqian; Xu, Yongxiao

2015-06-01

Four coumarin benzothiazole derivatives, N-(benzo[d]thiazol-2-yl)-2-oxo-2H-chromene-3-carboxamide (1), (Z)-N-(3-methylbenzo[d]thiazol-2(3H)-ylidene)-2-oxo-2H-chromene-3-carboxamide (2), 7-(diethylamino)-N-(benzo[d]thiazol-2-yl)-2-oxo-2H-chromene-3-carboxamide (3) and (Z)-7-(diethylamino)-N-(3-methylbenzo[d]thiazol-2(3H)-ylidene)-2-oxo-2H-chromene-3-carboxamide) (4), have been synthesized. Their crystal structures, photophysical properties in acetonitrile and recognition properties for cyanide anions have been investigated. All the compounds are generally planar, especially compound 1 exhibits perfect planarity with dihedral angle between benzothiazolyl group and coumarin group being only 3.63°. Coumarin benzothiazole compounds 1 and 3 can recognize cyanide anions by Michael addition reaction and compound 3 exhibits color change from yellow to colorless and green fluorescence was quenched completely, which can be observed by naked eye. Coumarin benzothiazolyliden compound 4 can recognize cyanide anions with fluorescence turn-on response based on the copper complex ensemble displacement mechanism.

A coumarin with an unusual structure from Cuphea ignea, its cytotoxicity and antioxidant activities.

PubMed

Moustafa, E S; Swilam, N F; Ghanem, O B; Hashim, A N; Nawwar, M A; Lindequist, U; Linscheid, M W

2018-04-02

Phenolic metabolite profiling using two dimensional paper chromatographic analysis (2 DPC) was used for assaying the complex mixture of phenolics of an aqueous ethanol aerial part extract of Cuphea ignea (Lytheraceae). A coumarin with a rare structure, namely, 7-hydroxy 3-methoxy coumarin 5-O-β-glucopyranoside was isolated from the investigated extract. The structure was elucidated by conventional methods and spectral analysis, including one and two dimensional NMR (1D and 2D NMR), as well as by interpretation of the spectra obtained by high resolution electrospray ionization mass technique (HRESIMS). The rare coumarin significantly inhibited reactive oxygen species production with an ED50 value of 6.31±1.64 μg/ml and 5.78±0.66 μg/ml as determined by the the free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH) and the oxygen radical absorption capacity (ORAC) assay respectively. The isolated coumarin presented a cytotoxic activity assessed by using the neutral red assay (NRU) against lung cancer cell line (H23) with IC50 of 40.38±2.75 μg/ml.

Rapid method for the determination of coumarin, vanillin, and ethyl vanillin in vanilla extract by reversed-phase liquid chromatography with ultraviolet detection.

PubMed

Ali, Laila; Perfetti, Gracia; Diachenko, Gregory

2008-01-01

A method is described for determining coumarin, vanillin, and ethyl vanillin in vanilla extract products. A product is diluted one-thousand-fold and then analyzed by reversed-phase liquid chromatography using a C18 column and a mobile phase consisting of 55% acetonitrile-45% aqueous acetic acid (1%) solution at a flow rate of 1.0 mL/min. Peaks are detected with a UV detector set at 275 nm. Vanilla extracts were spiked with 250, 500, and 1000 microg/g each of coumarin, vanillin, and ethyl vanillin. Recoveries averaged 97.4, 97.8, and 99.8% for coumarin, vanillin, and ethyl vanillin, respectively, with coefficient of variation values of 1.8, 1.3, and 1.3%, respectively. No significant difference was observed among the 3 spiking levels. A survey of 23 domestic and imported vanilla extract products was conducted using the method. None of the samples contained coumarin. The surveyed samples contained between 0.4 to 13.1 and 0.4 to 2.2 mg/g vanillin and ethyl vanillin, respectively.

Evaluation of the interaction of coumarins with biomembrane models studied by differential scanning calorimetry and Langmuir-Blodgett techniques.

PubMed

Sarpietro, Maria Grazia; Giuffrida, Maria Chiara; Ottimo, Sara; Micieli, Dorotea; Castelli, Francesco

2011-04-25

Three coumarins, scopoletin (1), esculetin (2), and esculin (3), were investigated by differential scanning calorimetry and Langmuir-Blodgett techniques to gain information about the interaction of these compounds with cellular membranes. Phospholipids assembled as multilamellar vesicles or monolayers (at the air-water interface) were used as biomembrane models. Differential scanning calorimetry was employed to study the interaction of these coumarins with multilamellar vesicles and to evaluate their absorption by multilamellar vesicles. These experiments indicated that 1-3 interact in this manner to different extents. The Langmuir-Blodgett technique was used to study the effect of these coumarins on the organization of phospholipids assembled as a monolayer. The data obtained were in agreement with those obtained in the calorimetric experiments.

β-glucuronidase inhibitory studies on coumarin derivatives.

PubMed

Khan, Khalid Mohammed; Fakhri, Muhammad Imran; Shaikh, Nimra Naveed; Saad, Syed Muhammad; Hussain, Shafqat; Perveen, Shahnaz; Choudhary, Muhammad Iqbal

2014-01-01

Twenty-three (23) derivatives of coumarin (5-27) were synthesized and screened for their in vitro β- glucuronidase (E. coli) inhibitory activities. Only three compounds, 7,8-dihydroxy-4-methyl-2H-chromen-2-one (9) (IC50 = 52.39 ± 1.85 µM), 3-chloro-6-hexyl-7-hydroxy-4-methyl-2H-chromen-2-one (18) (IC50 = 60.50 ± 0.87 µM), and 3,6- dichloro-7-hydroxy-4-methyl-2H-chromen-2-one (15) (IC50 = 380.26 ± 0.92 µM) displayed activities against β- glucuronidase as compared to standard D-saccharic acid 1,4-lactone (IC50 = 45.75 ± 2.16 µM). The results indicated that the activity of the synthetic coumarins depends upon the substituents present on the coumarin skeleton.

Analysis of limette and bergamot distilled essential oils by HPLC.

PubMed

Buiarelli, Francesca; Cartoni, Giampaolo; Coccioli, Franco; Jasionowska, Renata; Mazzarino, Monica

2002-04-01

This work examines the distilled essential oils of limette and bergamot in order to assess the presence of low volatile substances such as coumarins (bergapten) which, being toxic, must be eliminated before using these oils in the food industry. The quantitative determination of coumarins was carried out by spectrofluorimetric detection. The substances present in the chromatograms, obtained by HPLC with UV detection at 254 nm, were then identified. Moreover, a new coumarin that is present in small quantities was identified using HPLC-MS.

Supercritical CO2 Extraction of Lavandula angustifolia Mill. Flowers: Optimisation of Oxygenated Monoterpenes, Coumarin and Herniarin Content.

PubMed

Jerković, Igor; Molnar, Maja; Vidović, Senka; Vladić, Jelena; Jokić, Stela

2017-11-01

Lavandula angustifolia is good source of oxygenated monoterpenes containing coumarins as well, which are all soluble in supercritical CO 2 (SC-CO 2 ). The study objective is to investigate SC-CO 2 extraction parameters on: the total yield; GC-MS profile of the extracts; relative content of oxygenated monoterpenes; the amount of coumarin and herniarin; and to determine optimal SC-CO 2 extraction conditions by response surface methodology (RSM). SC-CO 2 extraction was performed under different pressure, temperature and CO 2 flow rate determined by Box-Behnken design (BBD). The sample mass and the extraction time were kept constant. The chemical profiles and relative content of oxygenated monoterpenes (as coumarin equivalents, CE) were determined by GC-MS. Coumarin and herniarin concentrations were dosed by HPLC. SC-CO 2 extracts contained linalool (57.4-217.9 mg CE/100 g), camphor (10.6-154.4 mg CE/100 g), borneol (6.2-99.9 mg CE/100 g), 1,8-cineole (5.0-70.4 mg CE/100 g), linalyl acetate (86.1-267.9 mg CE/100 g), coumarin (0.95-18.16 mg/100 g), and herniarin (0.95-13.63 mg/100 g). The interaction between the pressure and CO 2 flow rate as well as between the temperature and CO 2 flow rate showed statistically significant influence on the extraction yield. Applying BBD, the optimum extraction conditions for higher monoterpenes and lower coumarin content were at 10 MPa, 41°C and CO 2 flow rate 2.3 kg/h, and at 30 MPa, 50°C and CO 2 flow rate 3 kg/h for higher monoterpenes and coumarin content. SC-CO 2 extraction is a viable technique for obtaining lavender extracts with desirable flavour components. The second-order model based on BBD predicts the results for SC-CO 2 extraction quite satisfactorily. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

A prodrug approach to the use of coumarins as potential therapeutics for superficial mycoses.

PubMed

Mercer, Derry K; Robertson, Jennifer; Wright, Kristine; Miller, Lorna; Smith, Shane; Stewart, Colin S; O Neil, Deborah A

2013-01-01

Superficial mycoses are fungal infections of the outer layers of the skin, hair and nails that affect 20-25% of the world's population, with increasing incidence. Treatment of superficial mycoses, predominantly caused by dermatophytes, is by topical and/or oral regimens. New therapeutic options with improved efficacy and/or safety profiles are desirable. There is renewed interest in natural product-based antimicrobials as alternatives to conventional treatments, including the treatment of superficial mycoses. We investigated the potential of coumarins as dermatophyte-specific antifungal agents and describe for the first time their potential utility as topical antifungals for superficial mycoses using a prodrug approach. Here we demonstrate that an inactive coumarin glycone, esculin, is hydrolysed to the antifungal coumarin aglycone, esculetin by dermatophytes. Esculin is hydrolysed to esculetin β-glucosidases. We demonstrate that β-glucosidases are produced by dermatophytes as well as members of the dermal microbiota, and that this activity is sufficient to hydrolyse esculin to esculetin with concomitant antifungal activity. A β-glucosidase inhibitor (conduritol B epoxide), inhibited antifungal activity by preventing esculin hydrolysis. Esculin demonstrates good aqueous solubility (<6 g/l) and could be readily formulated and delivered topically as an inactive prodrug in a water-based gel or cream. This work demonstrates proof-of-principle for a therapeutic application of glycosylated coumarins as inactive prodrugs that could be converted to an active antifungal in situ. It is anticipated that this approach will be applicable to other coumarin glycones.

A Prodrug Approach to the Use of Coumarins as Potential Therapeutics for Superficial Mycoses

PubMed Central

Mercer, Derry K.; Robertson, Jennifer; Wright, Kristine; Miller, Lorna; Smith, Shane; Stewart, Colin S.; O′Neil, Deborah A.

2013-01-01

Superficial mycoses are fungal infections of the outer layers of the skin, hair and nails that affect 20–25% of the world's population, with increasing incidence. Treatment of superficial mycoses, predominantly caused by dermatophytes, is by topical and/or oral regimens. New therapeutic options with improved efficacy and/or safety profiles are desirable. There is renewed interest in natural product-based antimicrobials as alternatives to conventional treatments, including the treatment of superficial mycoses. We investigated the potential of coumarins as dermatophyte-specific antifungal agents and describe for the first time their potential utility as topical antifungals for superficial mycoses using a prodrug approach. Here we demonstrate that an inactive coumarin glycone, esculin, is hydrolysed to the antifungal coumarin aglycone, esculetin by dermatophytes. Esculin is hydrolysed to esculetin β-glucosidases. We demonstrate that β-glucosidases are produced by dermatophytes as well as members of the dermal microbiota, and that this activity is sufficient to hydrolyse esculin to esculetin with concomitant antifungal activity. A β-glucosidase inhibitor (conduritol B epoxide), inhibited antifungal activity by preventing esculin hydrolysis. Esculin demonstrates good aqueous solubility (<6 g/l) and could be readily formulated and delivered topically as an inactive prodrug in a water-based gel or cream. This work demonstrates proof-of-principle for a therapeutic application of glycosylated coumarins as inactive prodrugs that could be converted to an active antifungal in situ. It is anticipated that this approach will be applicable to other coumarin glycones. PMID:24260474

Purification of coumarin compounds from Cortex fraxinus by adsorption chromatography.

PubMed

Yu, Minglan; Sun, Ailing; Zhang, Yongqing; Liu, Renmin

2014-10-01

In this paper, a chromatographic method for isolation and purification of coumarin compounds from Cortex fraxinus was established by using Superose 12 as the separation media for the first time. The conditions for separation were optimized. Four kinds of coumarin compounds including aesuletin, aesculin, fraxetin and fraxin were obtained. The purity of these compounds were 98.5, 99.1, 97.9 and 97.3%, respectively, which were determined by HPLC area normalization method. The chemical structures of the separated compounds were identified according to (1)H and (13)C nuclear magnetic resonance data. The retention behavior of the separated coumarin compounds on Superose 12 was also discussed. The retention is based on a mixture of hydrogen bonding and hydrophobic interactions between the coumarin compounds and the residues of the cross-linking reagents used in the manufacturing process of Superose 12. The results of this paper indicate that Superose 12 is not only suitable for size-exclusion chromatography of proteins and other biological macromolecules but also for low-molecular-weight natural products. © The Author [2013]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

[Quantitative method for simultaneous assay of four coumarins with one marker in Fraxini Cortex].

PubMed

Feng, Weihong; Wang, Zhimin; Zhang, Qiwei; Liu, Limei; Wang, Jinyu; Yang, Fei

2011-07-01

To establish a new quantitative method for simultaneous determination of multi-coumarins in Fraxini Cortex by using one chemical reference substance, and validate its feasibilities. The new quality evaluation method, quantitative analysis of multi-components by singer-marker (QAMS), was established and validated with Fraxini Cortex. Four main coumarins were selected as analytes to evaluate the quality and their relative correlation factors (RCF) were determined by HPLC-DAD. Within the linear range, the values of RCF at 340 nm of aesculin to asculetin, fraxin and fraxetin were 1.771, 0.799, 1.409, respectively. And the contents of aesculin in samples of Fraxini Cortex were authentically determined by the external standard method, and the contents of the three other coumarins were calculated by their RCF. The contents of these four coumarins in all samples were also determined by the external standard method. Within a certain range, the RCF had a good reproducibility (RSD 2.5%-3.9%). Significant differences were not observed between the quantitative results of two methods. It is feasible and suitable to evaluate the quality of Fraxini Cortex and its Yinpian by QAMS.

Magnetic nanoparticles modified with DTPA-AMC-rare earth for fluorescent and magnetic resonance dual mode imaging.

PubMed

Liu, Zengchen; Li, Bo; Wang, Baodui; Yang, Zhengyin; Wang, Qin; Li, Tianrong; Qin, Dongdong; Li, Yong; Wang, Mingfang; Yan, Mihui

2012-07-28

In the present study, we report new water-soluble cell fluorescence imaging and contrast agents that are based on DTPA-AMC(7-amino-4-methyl coumarin)-Eu(3+) and DTPA-AMC(7-amino-4-methyl coumarin)-Gd(3+) compounds conjugated to Fe(3)O(4) NPs via a PEG-NH(2) linker. The novel Fe(3)O(4) NP-conjugates present two main advantages for cell fluorescence labelling: water solubility and targeting ability. The in vitro experiments demonstrate that water-soluble Fe(3)O(4) NPs-DBI-PEG-NH-DTPA-AMC(7-amino-4-methyl coumarin)-Eu(3+) has excellent cell permeating activity. Moreover, the relaxation rate test of Fe(3)O(4) NPs-DBI-PEG-NH-DTPA-AMC(7-amino-4-methyl coumarin)-Gd(3+) shows a higher T1 relaxation effect than traditional DTPA-Gd(3+) MRI agents. According to in vivo liver MRI experiments, better contrast of the liver was achieved after addition of Fe(3)O(4) NPs-DBI-PEG-NH-DTPA-AMC(7-amino-4-methyl coumarin)-Gd(3+). The results will provide a significant guide for researchers exploring the biomedical applications of superparamagnetic Fe(3)O(4) NPs.

Review on Natural Coumarin Lead Compounds for Their Pharmacological Activity

PubMed Central

Venugopala, K. N.; Rashmi, V.; Odhav, B.

2013-01-01

Coumarin (2H-1-benzopyran-2-one) is a plant-derived natural product known for its pharmacological properties such as anti-inflammatory, anticoagulant, antibacterial, antifungal, antiviral, anticancer, antihypertensive, antitubercular, anticonvulsant, antiadipogenic, antihyperglycemic, antioxidant, and neuroprotective properties. Dietary exposure to benzopyrones is significant as these compounds are found in vegetables, fruits, seeds, nuts, coffee, tea, and wine. In view of the established low toxicity, relative cheapness, presence in the diet, and occurrence in various herbal remedies of coumarins, it appears prudent to evaluate their properties and applications further. PMID:23586066

Tyrosinase inhibitor activity of coumarin-resveratrol hybrids.

PubMed

Fais, Antonella; Corda, Marcella; Era, Benedetta; Fadda, M Benedetta; Matos, Maria Joao; Quezada, Elias; Santana, Lourdes; Picciau, Carmen; Podda, Gianni; Delogu, Giovanna

2009-07-13

In the present work we report on the contribution of the coumarin moiety to tyrosinase inhibition. Coumarin-resveratrol hybrids 1-8 have been resynthesized to investigate the structure-activity relationships and the IC(50) values of these compounds were measured. The results showed that these compounds exhibited tyrosinase inhibitory activity. Compound 3-(3',4',5'-trihydroxyphenyl)-6,8-dihydroxycoumarin (8)is the most potentcompound (0.27 mM), more so than umbelliferone (0.42 mM), used as reference compound. The kinetic studies revealed that compound 8 caused non-competitive tyrosinase inhibition.

The essential role of coumarin secretion for Fe acquisition from alkaline soil

PubMed Central

Clemens, Stephan; Weber, Michael

2016-01-01

ABSTRACT Plant productivity is limited by the scarcity of the essential micronutrient iron particularly in alkaline soils. The root secretion of phenolics has long been recognized as a component of the acidification-reduction strategy to acquire iron (strategy I). However, very little molecular insight into this process was available until recently several research groups independently discovered the important role of coumarins for the growth of Arabidopsis thaliana under Fe-limited conditions. Genome-wide analyses of iron deficiency responses, mutant screening and metabolomics experiments all converged on the finding that the synthesis and root exudation of scopoletin, esculetin and other coumarins is essential for iron uptake from substrates with low iron availability. Here we describe the evidence supporting this conclusion and discuss important questions that now have to be addressed in order to better understand the mechanistic basis of coumarin-dependent iron uptake and its significance within the plant kingdom. PMID:26618918

Coumarins as cholinesterase inhibitors: A review.

PubMed

de Souza, Luana G; Rennã, Magdalena N; Figueroa-Villar, Jose D

2016-07-25

The first report in literature of the isolation of coumarin was in the year 1820. After this report, other papers were published demonstrating the isolation and synthesis of coumarin and analogues. These compounds have been studying along the years for several different pathologies. One of these pathologies was Alzheimer's disease (AD), being the main cause of dementia in the contemporary world. There are two hypotheses to explain the pathogenesis mechanism and disease symptoms, then having the "amyloid hypothesis" and the "cholinergic hypothesis". Some drugs for AD are based on the theory of "cholinergic hypothesis", which objective is to increase the concentration of ACh in the synaptic cleft by the inhibition of cholinesterases. Over the last twenty years, many studies with coumarins compounds were reported as cholinesterases inhibitors. The aim of the present review is to discuss the studies and development of new compounds for AD treatment. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Influence of solvent and substituent on excited state characteristics of laser grade coumarin dyes.

PubMed

Sharma, Vijay K; Saharo, P D; Sharma, Neera; Rastogi, Ramesh C; Ghoshal, S K; Mohan, D

2003-04-01

Absorption and fluorescence emission of 4 and 7 substituted coumarins viz. C 440, C 490, C 485 and C 311 have been studied in various polar and non-polar organic solvents. These coumarin dyes are substituted with alkyl, amine and fluorine groups at 4- and 7-positions. They give different absorption and emission spectra in different solvents. The study leads to a possible assignment of energy level scheme for such coumarins including the effect on ground state and excited state dipole moments due to substitutions. Excited state dipole moments of these dyes are calculated by solvetochromic data experimentally and theoretically these are calculated by PM 3 method. The dipole moments in excited state, for all molecules investigated here, are higher than the corresponding values in the ground state. The increase in dipole moment has been explained in terms of the nature of excited state and resonance structure.

Determination of coumarins in the roots of Angelica dahurica by supercritical fluid chromatography.

PubMed

Pfeifer, Isabella; Murauer, Adele; Ganzera, Markus

2016-09-10

The fact that supercritical fluid chromatography (SFC) offers many desirable features is known for a long time. Yet, the number of applications on natural products is still limited, because robust and user-friendly instrumentation became available just a few years ago. As coumarins hardly have been studied by this technique we developed the first SFC assay for their determination in crude plant material. After method optimization eight standard compounds, including simple coumarins, linear and angular furanocoumarins, could be baseline separated in 6min using an Acquity UPC(2) CSH Fluoro-Phenyl 1.7μm column with supercritical CO2, methanol and diethylamine as mobile phase. Method validation confirmed that the assay is linear (R(2)≥0.9995), precise (intra-day variation≤5.8%; inter-day variation≤4.4%) and accurate (recovery rates from 96.5 to 104.2%). Detection limits determined at 300nm were below 2ng on-column, and the method showed to be well suited for the analysis of coumarins in Angelica dahurica roots. It was observed that qualitative as well as quantitative composition vary significantly. In all samples Imperatorin (0.09-0.28%) was the major coumarin, followed either by Isoimperatorin or Oxypeucedanin; the total coumarin content ranged from 0.16 to 0.77%. The results were in good agreement to published data, so that because of its speed and green nature SFC is definitely an interesting alternative for the analysis of this important class of natural products. Copyright © 2016 Elsevier B.V. All rights reserved.

In silico genotoxicity of coumarins: application of the Phenol-Explorer food database to functional food science.

PubMed

Guardado Yordi, E; Matos, M J; Pérez Martínez, A; Tornes, A C; Santana, L; Molina, E; Uriarte, E

2017-08-01

Coumarins are a group of phytochemicals that may be beneficial or harmful to health depending on their type and dosage and the matrix that contains them. Some of these compounds have been proven to display pro-oxidant and clastogenic activities. Therefore, in the current work, we have studied the coumarins that are present in food sources extracted from the Phenol-Explorer database in order to predict their clastogenic activity and identify the structure-activity relationships and genotoxic structural alerts using alternative methods in the field of computational toxicology. It was necessary to compile information on the type and amount of coumarins in different food sources through the analysis of databases of food composition available online. A virtual screening using a clastogenic model and different software, such as MODESLAB, ChemDraw and STATISTIC, was performed. As a result, a table of food composition was prepared and qualitative information from this data was extracted. The virtual screening showed that the esterified substituents inactivate molecules, while the methoxyl and hydroxyl substituents contribute to their activity and constitute, together with the basic structures of the studied subclasses, clastogenic structural alerts. Chemical subclasses of simple coumarins and furocoumarins were classified as active (xanthotoxin, isopimpinellin, esculin, scopoletin, scopolin and bergapten). In silico genotoxicity was mainly predicted for coumarins found in beer, sherry, dried parsley, fresh parsley and raw celery stalks. The results obtained can be interesting for the future design of functional foods and dietary supplements. These studies constitute a reference for the genotoxic chemoinformatic analysis of bioactive compounds present in databases of food composition.

Coumarin incorporated triazoles: a new class of anticonvulsants.

PubMed

Bhat, Mashooq A; Al-Omar, Mohammed A

2011-01-01

A series of coumarin incorporated 1,2,4- triazole compounds (1-14) were evaluated for their possible anticonvulsant and neurotoxic properties, log P values, pharmacophoric mapping and three dimensional structure analysis. Compound (6) with para-fluoro substitution showed significant anticonvulsant activity.

[Coumarins of Anemone raddeana Regel and their biological activity].

PubMed

Ren, Feng-Zhi; Chen, Shu-Hong; Zheng, Zhi-Hui; Zhang, Xue-Xia; Li, Li-Hong; Dong, Ai-Hua

2012-02-01

To study the coumarins of Anemone raddeana Regel, the compounds were separated by silica gel column chromatography and HPLC. Their structures were identified by their physicochemical property and spectral analysis. Two new compounds were isolated and identified as 4, 7-dimethoxyl-5-methyl-6-hydroxy coumarin (1) and 4, 7-dimethoxyl-5-formyl-6-hydroxycoumarin (2). The bioassays indicated that compounds 1 and 2 could significantly inhibit the proliferation of cancer cell, and showed the agonist effect on the transactivity of retinoic acid receptor-alpha (RARalpha). In addition, the two compounds had inhibitory effect against human leukocyte elastase (HLE).

Simultaneous quantification of polymethoxylated flavones and coumarins in Fructus aurantii and Fructus aurantii immaturus using HPLC-ESI-MS/MS.

PubMed

Chen, Hai-Fang; Zhang, Wu-Gang; Yuan, Jin-Bin; Li, Yan-Gang; Yang, Shi-Lin; Yang, Wu-Liang

2012-02-05

The major lipid-soluble constituents in Fructus aurantii (zhiqiao) and Fructus aurantii immaturus (zhishi) are polymethoxylated flavones (PMFs) and coumarins. In the present study, a high-performance liquid chromatography with electrospray ionization tandem mass spectrometry method was developed to quantify PMFs (nobiletin, tangeretin, 5-hydroxy-6,7,8,4'-tetramethoxyflavone, and natsudaidai) and coumarins (marmin, meranzin hydrate, and auraptene) simultaneously. PMFs and coumarins were detected by electrospray ionization tandem mass spectrometry in positive ion mode and quantified with multiple reaction monitor. Samples were separated on a Diamonsil C₁₈ (150 mm × 4.6 mm, 5 μm) column using acetonitrile and formic acid-water solution as a mobile phase in gradient mode with a flow rate at 0.5 mL/min. All calibration curves showed good linearity (r² > 0.9977) within the test ranges. Variations of the intraday and interday precisions were less than 4.07%. The recoveries of the components were within the range of 95.79%-105.04% and the relative standard deviations were less than 3.82%. The method developed was validated with acceptable accuracy, precision, and extraction recoveries and can be applied for the identification and quantification of four PMFs and three coumarins in citrus herbs. Copyright © 2011 Elsevier B.V. All rights reserved.

Distribution Assessments of Coumarins from Angelicae Pubescentis Radix in Rat Cerebrospinal Fluid and Brain by Liquid Chromatography Tandem Mass Spectrometry Analysis.

PubMed

Yang, Yan-Fang; Zhang, Lei; Yang, Xiu-Wei

2018-01-20

Angelicae Pubescentis Radix (APR) is a widely-used traditional Chinese medicine. Pharmacological studies have begun to probe its biological activities on neurological disorders recently. To assess the brain penetration and distribution of APR, a validated ultra-performance liquid chromatography tandem mass spectrometry method was applied to the simultaneous determinations of the main coumarins from APR in the rat cerebrospinal fluid (CSF) and brain after oral administration of APR extract, including psoralen, xanthotoxin, bergapten, isoimperatorin, columbianetin, columbianetin acetate, columbianadin, oxypeucedanin hydrate, angelol B, osthole, meranzin hydrate and nodakenetin. Most of the tested coumarins entered the rat CSF and brain quickly, and double-peak phenomena in concentration-time curves were similar to those of their plasma pharmacokinetics. Columbianetin had the highest concentration in the CSF and brain, while psoralen and columbianetin acetate had the largest percent of CSF/plasma and brain/plasma, indicating that these three coumarins may be worthy of further research on the possible nervous effects. Correlations between the in vivo brain distributions and plasma pharmacokinetics of these coumarins were well verified. These results provided valuable information for the overall in vivo brain distribution characteristics of APR and also for its further studies on the active substances for the central nervous system.

Trypanocidal constituents in plants: 7. Mammea-type coumarins.

PubMed

Reyes-Chilpa, Ricardo; Estrada-Muñiz, Elizabeth; Vega-Avila, Elisa; Abe, Fumiko; Kinjo, Junei; Hernández-Ortega, Simón

2008-08-01

Calophyllum brasiliense and Mammea americana (Clusiaceae) are two trees from the tropical rain forests of the American continent. A previous screening showed high trypanocidal activity in the extracts of these species. Several mammea-type coumarins, triterpenoids and biflavonoids were isolated from the leaves of C. brasiliense. Mammea A/AA was obtained from the fruit peels of M. americana. These compounds were tested in vitro against epimastigotes and trypomastigotes of Trypanosoma cruzi, the etiologic agent of Chagas disease. The most potent compounds were mammea A/BA, A/BB, A/AA, A/BD and B/BA, with MC100 values in the range of 15 to 90 microg/ml. Coumarins with a cyclized gamma,gamma-dimethylallyl substituent on C-6, such as mammea B/BA, cyclo F + B/BB cyclo F, and isomammeigin, showed MC100 values > 200 microg/ml. Several active coumarins were also tested against normal human lymphocytes in vitro, which showed that mammea A/AA and A/BA were not toxic. Other compounds from C. brasiliense, such as the triterpenoids, friedelin, canophyllol, the biflavonoid amentoflavone, and protocatechuic and shikimic acids, were inactive against the epimastigotes. The isopropylidenedioxy derivative of shikimic acid was inactive, and its structure was confirmed by X-ray diffraction. Our results suggest that mammea-type coumarins could be a valuable source of trypanocidal compounds.

Evaluation in vitro and in vivo of dimethicone transdermal therapeutic systems. Influence of propylene glycol on drug release.

PubMed

Ritschel, W A; Nayak, P M

1987-03-01

Coumarin-containing transdermal drug delivery systems were studied in vitro for drug release and in vivo in rats for drug absorption. The matrix of the transdermal delivery system, dimethicone, was a commercially available silicone elastomer. The devices containing 1, 3 and 5% coumarin released in vitro 8.8 (87.4%), 23.4 (74.5%) and 31.6 mg (63.3%) of drug within 24 h. The device containing 5% coumarin was selected for further studies in which 5, 10, 20, 30, 50 and 70% propylene glycol was added. Up to 20% propylene glycol content did not change the amount released. The preparations with 30, 50 and 70% propylene glycol released 69.3, 73.6 and 87.9%, respectively. The 50 and 70% preparations were physically not acceptable. Only the preparations containing 5% coumarin without propylene glycol and 5% coumarin and 30% propylene glycol in the elastomer were evaluated in vivo. The area under the blood level-time curve of the propylene glycol-containing system was twice that of the device without propylene glycol. Blood levels were maintained between about 2 micrograms/ml and 5 micrograms/ml during the time the device was kept on the skin (24 h).

Irritant and cytotoxic coumarins from Angelica glauca Edgew roots.

PubMed

Saeed, M Asif; Sabir, A W

2008-01-01

Irritant and cytotoxic potentiality of six coumarins, isolated for the first time from the roots of Angelica glauca identified as 5,6,7-trimethoxycoumarin, 6-methoxy-7,8-methylenedioxycoumarin, bergapten, decursinol angelate, decursin, and nodakenetin, were investigated. The irritant potential was explored by open mouse ear assay, evaluating their ID(50) after acute and by IU (Irritant units) after chronic effects, while the cytotoxic capability was explored by their LC(50), using brine shrimp (Artemia salina) larvae (nauplii). All the coumarins exhibited well-defined irritancy on mouse's ears, compared with the positive controlled euphorbium reaction and cytotoxic response against brine shrimp larvae, compared with the positive control colchicine. Decursinol angelate and decursin were the most potent and persistent irritant compounds with least ID(50), whose reactions lasted for 48 h. 6-Methoxy-7,8-methylenedioxycoumarin and bergaten revealed an intermediate irritant reactions, while 5,6,7-trimethoxycoumarin and nodakenetin displayed the least irritant and least persistent reactions on mouse ears. Both decursin and decursinol angelate also appeared to be the stronger cytotoxic agents than other coumarins. 5,6,7-trimethoxycoumarin displayed an intermediate cytotoxic behaviour, while other three coumarins, i.e., 6-methoxy-7,8-methylenedioxycoumarin, bergapten, and nodakenetin, exhibited the least cytotoxic capacity against brine shrimp larvae.

The future prospects of pharmacogenetics in oral anticoagulation therapy

PubMed Central

Kamali, Farhad; Pirmohamed, Munir

2006-01-01

Coumarins are the mainstay of oral anticoagulation for the treatment and prophylaxis of thromboembolic disorders. They have a narrow therapeutic index and regular monitoring is therefore required to avoid serious adverse effects. There is wide interindividual variability in dosage requirements, which makes anticoagulation response unpredictable. Current dosing titrations are haphazard and inconvenient and poor initial control leads to morbidity, and occasional mortality, because of bleeding and further thromboembolism. Recent discoveries have helped to characterize the factors that contribute to the interindividual variability in responses to coumarins. Patient and environmental factors that affect anticoagulation response to coumarins include age, body size, dietary vitamin K status, concurrent disease and drug interactions. More recently, single nucleotide polymorphisms in the 2C9 isoform of cytochrome P450 (CYP2C9) and vitamin K epoxide reductase (VKOR) have been shown to make significant contributions to the variability in coumarin dosage requirements. Polymorphisms in other genes that mediate the actions of coumarins may also contribute to this variability. Racial and cultural differences influence dosage requirements, which can be explained, at least in part, by genetic and dietary factors. Incorporation of genetic and environmental factors could help in the prediction of more individualized loading and maintenance doses for safer anticoagulation therapy. PMID:16722840

Allosteric Partial Inhibition of Monomeric Proteases. Sulfated Coumarins Induce Regulation, not just Inhibition, of Thrombin

PubMed Central

Verespy III, Stephen; Mehta, Akul Y.; Afosah, Daniel; Al-Horani, Rami A.; Desai, Umesh R.

2016-01-01

Allosteric partial inhibition of soluble, monomeric proteases can offer major regulatory advantages, but remains a concept on paper to date; although it has been routinely documented for receptors and oligomeric proteins. Thrombin, a key protease of the coagulation cascade, displays significant conformational plasticity, which presents an attractive opportunity to discover small molecule probes that induce sub-maximal allosteric inhibition. We synthesized a focused library of some 36 sulfated coumarins to discover two agents that display sub-maximal efficacy (~50%), high potency (<500 nM) and high selectivity for thrombin (>150-fold). Michaelis-Menten, competitive inhibition, and site-directed mutagenesis studies identified exosite 2 as the site of binding for the most potent sulfated coumarin. Stern-Volmer quenching of active site-labeled fluorophore suggested that the allosteric regulators induce intermediate structural changes in the active site as compared to those that display ~80–100% efficacy. Antithrombin inactivation of thrombin was impaired in the presence of the sulfated coumarins suggesting that allosteric partial inhibition arises from catalytic dysfunction of the active site. Overall, sulfated coumarins represent first-in-class, sub-maximal inhibitors of thrombin. The probes establish the concept of allosteric partial inhibition of soluble, monomeric proteins. This concept may lead to a new class of anticoagulants that are completely devoid of bleeding. PMID:27053426

Synergism of coumarins from the Chinese drug Zanthoxylum nitidum with antibacterial agents against methicillin-resistant Staphylococcus aureus (MRSA).

PubMed

Zuo, Guo-Ying; Wang, Chun-Juan; Han, Jun; Li, Yu-Qing; Wang, Gen-Chun

2016-12-15

Methicillin-resistant Staphylococcus aureus (MRSA) poses a serious therapeutic challenge in current clinic and new drug development. Natural coumarins have diverse bioactivities and the potential of resistance modifying effects. This study is to present in-depth evaluations of in vitro antimicrobial activities of four natural coumarins 5-geranyloxy-7-methoxycoumarin (Gm, 1), (5,7-dimethoxy-8-prenyloxycoumarin (artanin, Ar, 2)), isopimpinellin (Is, 3) and phellopterin (Ph, 4) from Zanthoxylum nitidum (Roxb.) DC. (Rutaceae) extracts, focusing on their potential restoration the activity of conventional antibacterial agents against clinical MRSA strains. Bioactivity-guided fractionation and spectral analyses were used to isolate the coumarins and identify the structures, respectively. The double broth microdilution method was used to assay the coumarins' alone activity. The classic checkerboard microdilution and dynamic time-killing methods were used to evaluate combinatory effects. The four plant coumarins Gm (1), Ar (2), Is (3) and Ph (4) were isolated and identified from Z. nitidum extracts. Coumarins 1-4 displayed promising inhibition against both MSSA and MRSA with minimal inhibitory concentrations (MICs) of 8-64µg/ml, but very weak against Gram-negative pathogen and yeast with MICs of 256 to ≥1024µg/ml. The geranyloxy and prenyloxy substitutions showed to be more active than the methoxy substitution on the coumarin skeletons. 1-4 also showing different extent of synergism with a total of eight conventional antibacterial agents, i.e. chloramphenicol (CL), gentamicin (CN), fosfomycin (FF), levofloxacin (LE), minocycline (MI), piperacillin/tazobactam (P/T), teicoplanin (TE) and vancomycin (VA) against ten clinical MRSA strains. Four to ten of the tested MRSA strains showed bacteriostatic synergy in the eleven combinations. The anti-MRSA modifying effects were related to different arrangement in the combinations with fractional inhibitory concentration indices (FICIs) from 0.187 to 1.125 and the three combinations CN (Is), CL (Ph) and MI (Gm) were the best ones. The enhancement of activity was also shown by 2-64 of dose reduction indices (DRIs) of the combined MICs, with VA (Ph) combination resulted the biggest DRI. The resistance of MRSA to antibacterial agents could be reversed in the combinations of CL (Gm or Ph), LE (Ph) and MI (Is) following the Clinical and Laboratory Standards Institute (CLSI) criteria. Six combinations P/T (Gm), TE (Ar), CN (Is), VA (Ph) and CL (Gm or Ph) also showed bactericidal synergy with Δlog 10 CFU/ml >2 at 24h incubation. The coumarins showed high potentiating effects of the antibacterial agents against multi-drug resistant SA. The resistance reversal effect of CL, LE and MI warrants further pharmacological investigation on combinatory therapy for the sake of fighting against MRSA infections. Copyright © 2016 Elsevier GmbH. All rights reserved.

40 CFR 721.2155 - Alkoxyamino-alkyl-coumarin (generic).

Code of Federal Regulations, 2010 CFR

2010-07-01

...). 721.2155 Section 721.2155 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.2155 Alkoxyamino-alkyl-coumarin (generic). (a) Chemical substance and significant new uses...

Biotransformation of aesculin by human gut bacteria and identification of its metabolites in rat urine.

PubMed

Ding, Wei-Jun; Deng, Yun; Feng, Hao; Liu, Wei-Wei; Hu, Rong; Li, Xiang; Gu, Zhe-Ming; Dong, Xiao-Ping

2009-03-28

To observe the biotransformation process of a Chinese compound, aesculin, by human gut bacteria, and to identify its metabolites in rat urine. Representative human gut bacteria were collected from 20 healthy volunteers, and then utilized in vitro to biotransform aesculin under anaerobic conditions. At 0, 2, 4, 8, 12, 16, 24, 48 and 72 h post-incubation, 10 mL of culture medium was collected. Metabolites of aesculin were extracted 3 x from rat urine with methanol and analyzed by HPLC. For in vivo metabolite analysis, aesculetin (100 mg/kg) was administered to rats via stomach gavage, rat urine was collected from 6 to 48 h post-administration, and metabolite analysis was performed by LC/ESI-MS and MS/MS in the positive and negative modes. Human gut bacteria could completely convert aesculin into aesculetin in vitro. The biotransformation process occurred from 8 to 24 h post-incubation, with its highest activity was seen from 8 to 12 h. The in vitro process was much slower than the in vivo process. In contrast to the in vitro model, six aesculetin metabolites were identified in rat urine, including 6-hydroxy-7-gluco-coumarin (M1), 6-hydroxy-7-sulf-coumarin (M2), 6, 7-di-gluco-coumarin (M3), 6-glc-7-gluco-coumarin (M4), 6-O-methyl-7-gluco-coumarin (M5) and 6-O-methyl-7-sulf-coumarin (M6). Of which, M2 and M6 were novel metabolites. Aesculin can be transferred into aesculetin by human gut bacteria and is further modified by the host in vivo. The diverse metabolites of aesculin may explain its pleiotropic pharmaceutical effects.

Novel coumarin modified GLP-1 derivatives with enhanced plasma stability and prolonged in vivo glucose-lowering ability.

PubMed

Han, Jing; Sun, Lidan; Huang, Xun; Li, Zheng; Zhang, Chenyu; Qian, Hai; Huang, Wenlong

2014-12-01

The short biological half-life limits the therapeutic use of glucagon-like peptide-1 (GLP-1) and chemical modification to improve the interaction of peptides with serum albumin represents an effective strategy to develop long-acting peptide analogues. Coumarin, a natural product, is known to bind tightly to plasma proteins and possesses many biological activities. Therefore, we designed and synthesized a series of coumarin-modified GLP-1 derivatives, hypothesizing that conjugation with coumarin would retain the therapeutic effects and prolong the biological half-life of the conjugates. Four cysteine-modified GLP-1 analogues (1-4) were prepared using Gly8 -GLP-1(7-36)-NH2 peptide as a starting point. These analogues were conjugated with two coumarin maleimides to yield eight compounds (conjugates 6-13) for testing. Activation of human GLP-1 receptors, stability to enzymic inactivation in plasma and binding to human albumin were assessed in vitro. In vivo, effects on oral glucose tolerance tests (OGTT) in rats and on blood glucose levels in db/db mice were studied. Most conjugates showed well preserved receptor activation efficacy, enhanced albumin-binding properties and improved in vitro plasma stability and conjugate 7 was selected to undergo further assessment. In rats, conjugate 7 had a longer circulating t1/2 than exendin-4 or liraglutide. A prolonged antidiabetic effect of conjugate 7 was observed after OGTT in rats and a prolonged hypoglycaemic effect in db/db mice. Cysteine-specific coumarin conjugation with GLP-1 offers a useful approach to the development of long-acting incretin-based antidiabetic agents. Conjugate 7 is a promising long-lasting GLP-1 derivative deserving further investigation. © 2014 The British Pharmacological Society.

Novel coumarin modified GLP-1 derivatives with enhanced plasma stability and prolonged in vivo glucose-lowering ability

PubMed Central

Han, Jing; Sun, Lidan; Huang, Xun; Li, Zheng; Zhang, Chenyu; Qian, Hai; Huang, Wenlong

2014-01-01

Background and Purpose The short biological half-life limits the therapeutic use of glucagon-like peptide-1 (GLP-1) and chemical modification to improve the interaction of peptides with serum albumin represents an effective strategy to develop long-acting peptide analogues. Coumarin, a natural product, is known to bind tightly to plasma proteins and possesses many biological activities. Therefore, we designed and synthesized a series of coumarin-modified GLP-1 derivatives, hypothesizing that conjugation with coumarin would retain the therapeutic effects and prolong the biological half-life of the conjugates. Experimental Approach Four cysteine-modified GLP-1 analogues (1–4) were prepared using Gly8-GLP-1(7–36)-NH2 peptide as a starting point. These analogues were conjugated with two coumarin maleimides to yield eight compounds (conjugates 6–13) for testing. Activation of human GLP-1 receptors, stability to enzymic inactivation in plasma and binding to human albumin were assessed in vitro. In vivo, effects on oral glucose tolerance tests (OGTT) in rats and on blood glucose levels in db/db mice were studied. Key Results Most conjugates showed well preserved receptor activation efficacy, enhanced albumin-binding properties and improved in vitro plasma stability and conjugate 7 was selected to undergo further assessment. In rats, conjugate 7 had a longer circulating t1/2 than exendin-4 or liraglutide. A prolonged antidiabetic effect of conjugate 7 was observed after OGTT in rats and a prolonged hypoglycaemic effect in db/db mice. Conclusions and Implications Cysteine-specific coumarin conjugation with GLP-1 offers a useful approach to the development of long-acting incretin-based antidiabetic agents. Conjugate 7 is a promising long-lasting GLP-1 derivative deserving further investigation. PMID:25039358

Photophysics of a coumarin based Schiff base in solvents of varying polarities

NASA Astrophysics Data System (ADS)

Ghosh, Saptarshi; Roy, Nayan; Singh, T. Sanjoy; Chattopadhyay, Nitin

2018-01-01

The present work reports detailed photophysics of a coumarin based Schiff base, namely, (E)-7-(((8-hydroxyquinolin-2-yl)methylene)amino)-4-methyl-2H-chromen-2-one (HMC) in different solvents of varying polarity exploiting steady state absorption, fluorescence and time resolved fluorescence spectroscopy. The dominant photophysical features of HMC are discussed in terms of emission from an intramolecular charge transfer (ICT) excited state. Molecular orbital (MO) diagrams as obtained from DFT based computational analysis confirms the occurrence of charge transfer from 8‧-hydroxy quinoline moiety of the molecule to the coumarin part. The notable difference in the photophysical response of HMC from its analogous coumarin (C480) lies in a lower magnitude of fluorescence quantum yield of the former, particularly in the solvents of low polarity, which is rationalized by considering the higher rate of non-radiative decay of HMC in apolar solvents. Phosphorescence emission as well as phosphorescence lifetime of HMC has also been reported in 77 K frozen matrix.

[Case report. Phenprocoumon (Marcumar, Falithrom) as an unusual reason for coumarin poisoning in a dog].

PubMed

Lutze, G; Römhild, W; Elwert, J; Leppelt, J; Kutschmann, K

2003-01-01

Coumarin poisoning in dogs is not unusual and is in most cases caused by warfarin, a coumarin derivative which is used as a rodenticide. Competitive inhibition of vitamin K with an incomplete synthesis of the coagulation factors II, VII, IX and X can lead to a significant bleeding tendency. We observed a 3-year old male West Highland White Terrier with a reduced general condition and dyspnoea together with a massive haemothorax. Administration of vitamin K1 (3 mg/kg) led to a rapid improvement of the condition. Coagulation analysis revealed a prolonged activated recalcification time (ARCT), prothrombin time (PT) and aPTT with uncharacteristic thrombin time (TT); factor II, VII and X activities were reduced while factor V activity was normal, all of which are characteristic for coumarin poisoning. HPLC did not reveal the presence of warfarin but of phenoprocoumon, a drug used for thromboembolic prophylaxis in humans. This observation has not been described for dogs to date.

Comparisons of the spectroscopic and microbiological activities among coumarin-3-carboxylate, o-phenanthroline and zinc(II) complexes

NASA Astrophysics Data System (ADS)

Islas, María S.; Martínez Medina, Juan J.; Piro, Oscar E.; Echeverría, Gustavo A.; Ferrer, Evelina G.; Williams, Patricia A. M.

2018-06-01

Coumarins (2H-chromen-2-one) are oxygen-containing heterocyclic compounds that belong to the benzopyranones family. In this work we have synthesized different coordination complexes with coumarin-3-carboxylic acid (HCCA), o-phenanthroline (phen) and zinc(II). In the reported [Zn(CCA)2(H2O)2] complex, coumarin-3-carboxylate (CCA) is acting as a bidentate ligand while in the two prepared complexes, [Zn(phen)3]CCA(NO3) (obtained as a single crystal) and [Zn(CCA)2phen].4H2O, CCA is acting as a counterion of the complex cation [Zn(phen)3]+2 or coordinated to the metal center along with phen, respectively. These compounds were characterized on the basis of elemental analysis and thermogravimetry. NMR, FTIR and Raman spectroscopies of the compounds and the CCA potassium salt (KCCA) allow to determine several similarities and differences among them. Finally, their behavior against alkaline phosphatase enzyme and their antimicrobial activities were also measured.

Fluorescent Polymer Incorporating Triazolyl Coumarin Units for Cu2+ Detection via Planarization of Ict-Based Fluorophore

PubMed Central

Ngororabanga, Jean Marie Vianney; Du Plessis, Jacolien; Mama, Neliswa

2017-01-01

A novel fluorescent polymer with pendant triazolyl coumarin units was synthesized through radical polymerization. The polymer showed reasonable sensitivity and selectivity towards Cu2+ in acetonitrile in comparison to other tested metal ions with a significant quenching effect on fluorescence and blue shifting in the range of 20 nm. The blue shift was assigned to the conformation changes of the diethylamino group from the coumarin moiety which led to planarization of the triazolyl coumarin units. The possible binding modes for Cu2+ towards the polymer were determined through the comparison of the emission responses of the polymer, starting vinyl monomer and reference compound, and the triazole ring was identified as one of the possible binding sites for Cu2+. The detection limits of the polymer and vinyl monomer towards Cu2+ were determined from fluorescence titration experiments and a higher sensitivity (35 times) was observed for the polymer compared with its starting monomer. PMID:28867764

Fluorescent Polymer Incorporating Triazolyl Coumarin Units for Cu2+ Detection via Planarization of Ict-Based Fluorophore.

PubMed

Ngororabanga, Jean Marie Vianney; Du Plessis, Jacolien; Mama, Neliswa

2017-08-30

A novel fluorescent polymer with pendant triazolyl coumarin units was synthesized through radical polymerization. The polymer showed reasonable sensitivity and selectivity towards Cu 2+ in acetonitrile in comparison to other tested metal ions with a significant quenching effect on fluorescence and blue shifting in the range of 20 nm. The blue shift was assigned to the conformation changes of the diethylamino group from the coumarin moiety which led to planarization of the triazolyl coumarin units. The possible binding modes for Cu 2+ towards the polymer were determined through the comparison of the emission responses of the polymer, starting vinyl monomer and reference compound, and the triazole ring was identified as one of the possible binding sites for Cu 2+ . The detection limits of the polymer and vinyl monomer towards Cu 2+ were determined from fluorescence titration experiments and a higher sensitivity (35 times) was observed for the polymer compared with its starting monomer.

Antiproliferative effect of isopentenylated coumarins on several cancer cell lines.

PubMed

Kawaii, S; Tomono, Y; Ogawa, K; Sugiura, M; Yano, M; Yoshizawa, Y; Ito, C; Furukawa, H

2001-01-01

33 coumarins, mainly the simple isopentenylated coumarins and derived pyrano- and furanocoumarins, were examined for their antiproliferative activity towards several cancer and normal human cell lines. The pyrano- and furanocoumarins showed strong activity against the cancer cell lines, whereas they had weak antiproliferative activity against the normal human cell lines. The decreasing rank order of potency was osthenone (10), clausarin (25), clausenidin (26), dentatin (24), nordentatin (23), imperatorin (29), seselin (27), xanthyletin (21), suberosin (17), phebalosin (8) and osthol (12). The structure-activity relationship established from the results revealed that the 1,1-dimethylallyl and isopentenyl groups have an important role for antiproliferative activity.

Bio-pesticidal and anti-microbial coumarins from Angelica dahurica (Fisch. Ex Hoffm)

USDA-ARS?s Scientific Manuscript database

Angelica dahurica is an important traditional Chinese herb which is widely used in curing acne, ulcers, carbuncles, rheumatism, headaches and toothaches. A systematic antifungal bioassay-guided fractionation of the ethyl acetate extract from A. dahurica led to the isolation of six coumarins, namely...

Metabolome analysis of Arabidopsis thaliana roots identifies a key metabolic pathway for iron acquisition.

PubMed

Schmidt, Holger; Günther, Carmen; Weber, Michael; Spörlein, Cornelia; Loscher, Sebastian; Böttcher, Christoph; Schobert, Rainer; Clemens, Stephan

2014-01-01

Fe deficiency compromises both human health and plant productivity. Thus, it is important to understand plant Fe acquisition strategies for the development of crop plants which are more Fe-efficient under Fe-limited conditions, such as alkaline soils, and have higher Fe density in their edible tissues. Root secretion of phenolic compounds has long been hypothesized to be a component of the reduction strategy of Fe acquisition in non-graminaceous plants. We therefore subjected roots of Arabidopsis thaliana plants grown under Fe-replete and Fe-deplete conditions to comprehensive metabolome analysis by gas chromatography-mass spectrometry and ultra-pressure liquid chromatography electrospray ionization quadrupole time-of-flight mass spectrometry. Scopoletin and other coumarins were found among the metabolites showing the strongest response to two different Fe-limited conditions, the cultivation in Fe-free medium and in medium with an alkaline pH. A coumarin biosynthesis mutant defective in ortho-hydroxylation of cinnamic acids was unable to grow on alkaline soil in the absence of Fe fertilization. Co-cultivation with wild-type plants partially rescued the Fe deficiency phenotype indicating a contribution of extracellular coumarins to Fe solubilization. Indeed, coumarins were detected in root exudates of wild-type plants. Direct infusion mass spectrometry as well as UV/vis spectroscopy indicated that coumarins are acting both as reductants of Fe(III) and as ligands of Fe(II).

Simultaneous determination of five coumarins in Angelicae dahuricae Radix by HPLC/UV and LC-ESI-MS/MS.

PubMed

Park, Ah Yeon; Park, So-Young; Lee, Jaehyun; Jung, Mihye; Kim, Jinwoong; Kang, Sam Sik; Youm, Jeong-Rok; Han, Sang Beom

2009-10-01

Rapid, simple and reliable HPLC/UV and LC-ESI-MS/MS methods for the simultaneous determination of five active coumarins of Angelicae dahuricae Radix, byakangelicol (1), oxypeucedanin (2), imperatorin (3), phellopterin (4) and isoimperatorin (5) were developed and validated. The separation condition for HPLC/UV was optimized using a Develosil RPAQUEOUS C(30) column using 70% acetonitrile in water as the mobile phase. This HPLC/UV method was successful for providing the baseline separation of the five coumarins with no interfering peaks detected in the 70% ethanol extract of Angelicae dahuricae Radix. The specific determination of the five coumarins was also accomplished by a triple quadrupole tandem mass spectrometer equipped with an electrospray ionization source (LC-ESI-MS/MS). Multiple reaction monitoring (MRM) in the positive mode was used to enhance the selectivity of detection. The LC-ESI-MS/MS methods were successfully applied for the determination of the five major coumarins in Angelicae dahuricae Radix. These HPLC/UV and LC-ESI-MS/MS methods were validated in terms of recovery, linearity, accuracy and precision (intra- and inter-day validation). Taken together, the shorter analysis time involved makes these HPLC/UV and LC-ESI-MS/MS methods valuable for the commercial quality control of Angelicae dahuricae Radix extracts and its pharmaceutical preparations. Copyright (c) 2009 John Wiley & Sons, Ltd.

Mechanism of action of coumarin and silver(I)-coumarin complexes against the pathogenic yeast Candida albicans.

PubMed

Thati, Bhumika; Noble, Andy; Rowan, Raymond; Creaven, Bernadette S; Walsh, Maureen; McCann, Malachy; Egan, Denise; Kavanagh, Kevin

2007-08-01

The anti-fungal activity and mode of action of a range of silver(I)-coumarin complexes was examined. The most potent silver(I)-coumarin complexes, namely 7-hydroxycoumarin-3-carboxylatosilver(I), 6-hydroxycoumarin-3-carboxylatosilver(I) and 4-oxy-3-nitrocoumarinbis(1,10-phenanthroline)silver(I), had MIC80 values of between 69.1 and 4.6 microM against the pathogenic yeast Candida albicans. These compounds also reduced respiration, lowered the ergosterol content of cells and increased the trans-membrane leakage of amino acids. A number of the complexes disrupted cytochrome synthesis in the cell and induced the appearance of morphological features consistent with cell death by apoptosis. These compounds appear to act by disrupting the synthesis of cytochromes which directly affects the cell's ability to respire. A reduction in respiration leads to a depletion in ergosterol biosynthesis and a consequent disruption of the integrity of the cell membrane. Disruption of cytochrome biosynthesis may induce the onset of apoptosis which has been shown previously to be triggered by alteration in the location of cytochrome c. Silver(I)-coumarin complexes demonstrate good anti-fungal activity and manifest a mode of action distinct to that of the conventional azole and polyene drugs thus raising the possibility of their use when resistance to conventional drug has emerged or in combination with such drugs.

Pharmacogenetic Variation in Over 100 Genes in Patients Receiving Acenocumarol

PubMed Central

Gonzalez-Covarrubias, Vanessa; Urena-Carrion, Javier; Villegas-Torres, Beatriz; Cossío-Aranda, J. Eduardo; Trevethan-Cravioto, Sergio; Izaguirre-Avila, Raul; Fiscal-López, O. Javier; Soberon, Xavier

2017-01-01

Coumarins are widely prescribed worldwide, and in Mexico acenocumarol is the preferred form. It is well known that despite its efficacy, coumarins show a high variability for dose requirements. We investigated the pharmacogenetic variation of 110 genes in patients receiving acenocumarol using a targeted NGS approach. We report relevant population differentiation for variants on CYP2C8, CYP2C19, CYP4F11, CYP4F2, PROS, and GGCX, VKORC1, CYP2C18, NQO1. A higher proportion of novel-to-known variants for 10 genes was identified on 41 core pharmacogenomics genes related to the PK (29), PD (3), of coumarins, and coagulation proteins (9) including, CYP1A1, CYP3A4, CYP3A5, and F8, and a low proportion of novel-to-known variants on CYP2E1, VKORC1, and SULT1A1/2. Using a Bayesian approach, we identified variants influencing acenocumarol dosing on, VKORC1 (2), SULT1A1 (1), and CYP2D8P (1) explaining 40–55% of dose variability. A collection of pharmacogenetic variation on 110 genes related to the PK/PD of coumarins is also presented. Our results offer an initial insight into the use of a targeted NGS approach in the pharmacogenomics of coumarins in Mexican Mestizos. PMID:29218011

Caspase-1 Specific Light-Up Probe with Aggregation-Induced Emission Characteristics for Inhibitor Screening of Coumarin-Originated Natural Products.

PubMed

Lin, Hao; Yang, Haitao; Huang, Shuai; Wang, Fujia; Wang, Dong-Mei; Liu, Bin; Tang, Yi-Da; Zhang, Chong-Jing

2018-04-18

Caspase-1 is a key player in pyroptosis and inflammation. Caspase-1 inhibition is found to be beneficial to various diseases. Coumarin-originated natural products have an anti-inflammation function, but their direct inhibition effect to caspase-1 remains unexplored. To evaluate their interactions, the widely used commercial coumarin-based probe (Ac-YVAD-AMC) is not suitable, as the background signal from coumarin-originated natural products could interfere with the screening results. Therefore, fluorescent probes using a large Stokes shift could help solve this problem. In this work, we chose the fluorophore of tetraphenylethylene-thiophene (TPETH) with aggregation-induced emission characteristics and a large Stokes shift of about 200 nm to develop a molecular probe. Bioconjugation between TPETH and hydrophilic peptides (DDYVADC) through a thiol-ene reaction generated a light-up probe, C1-P3. The probe has little background signal in aqueous media and exerts a fluorescent turn-on effect in the presence of caspase-1. Moreover, when evaluating the inhibition potency of coumarin-originated natural products, the new probe could generate a true and objective result but not for the commercial probe (Ac-YVAD-AMC), which is evidenced by HPLC analysis. The quick light-up response and accurate screening results make C1-P3 very useful in fundamental study and inhibitior screening toward caspase-1.

Risk assessment of Soulatrolide and Mammea (A/BA+A/BB) coumarins from Calophyllum brasiliense by a toxicogenomic and toxicological approach.

PubMed

Gomez-Verjan, J C; Estrella-Parra, E; Vazquez-Martinez, E R; Gonzalez-Sanchez, I; Guerrero-Magos, G; Mendoza-Villanueva, D; Isus, L; Alfaro, A; Cerbón-Cervantes, M; Aloy, P; Reyes-Chilpa, R

2016-05-01

Calophyllum brasiliense (Calophyllaceae) is a tropical rain forest tree distributed in Central and South America. It is an important source of tetracyclic dipyrano coumarins (Soulatrolide) and Mammea type coumarins. Soulatrolide is a potent inhibitor of HIV-1 reverse transcriptase and displays activity against Mycobacterium tuberculosis. Meanwhile, Mammea A/BA and A/BB, pure or as a mixture, are highly active against several human leukemia cell lines, Trypanosoma cruzi and Leishmania amazonensis. Nevertheless, there are few studies evaluating their safety profile. In the present work we performed toxicogenomic and toxicological analysis for both type of compounds. Soulatrolide, and the Mammea A/BA + A/BB mixture (2.1) were slightly toxic accordingly to Lorke assay classification (DL50 > 3000 mg/kg). After a short-term administration (100 mg/kg/daily, orally, 1 week) liver toxicogenomic analysis revealed 46 up and 72 downregulated genes for Mammea coumarins, and 665 up and 1077 downregulated genes for Soulatrolide. Gene enrichment analysis identified transcripts involved in drug metabolism for both compounds. In addition, network analysis through protein-protein interactions, tissue evaluation by TUNEL assay, and histological examination revealed no tissue damage on liver, kidney and spleen after treatments. Our results indicate that both type of coumarins displayed a safety profile, supporting their use in further preclinical studies to determine its therapeutic potential. Copyright © 2016 Elsevier Ltd. All rights reserved.

Differential morphological, cytological and biochemical responses of two rice cultivars to coumarin

USDA-ARS?s Scientific Manuscript database

Plants are often exposed to allelochemicals in the environment produced by neighboring plants. Coumarin is a common allelochemical produced by many higher plants. Two cultivars (susceptible BS-2000 and less susceptible BR-41) of rice (Oryza sativa L.) were selected to compare their differential root...

21 CFR 189.130 - Coumarin.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Coumarin. 189.130 Section 189.130 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) SUBSTANCES PROHIBITED FROM USE IN HUMAN FOOD Substances Generally Prohibited From Direct Addition or Use as Human Food § 189...

Convenient Microscale Synthesis of a Coumarin Laser Dye Analog

ERIC Educational Resources Information Center

Aktoudianakis, Evangelos; Dicks, Andrew P.

2006-01-01

Coumarin (2H-1-benzopyran-2-one) and its derivatives constitute a fascinating class of organic substances that are utilized industrially in areas such as cosmetics, food preservatives, insecticides and fluorescent laser dyes. The product can be synthesized, purified, and characterized within two hours with benefits of microscale reactivity being…

Diversity-Oriented Synthesis of Coumarin-Linked Benzimidazoles via a One-Pot, Three-Step, Intramolecular Knoevenagel Cyclization.

PubMed

Yao, Po-Hsin Eric; Kumar, Sunil; Liu, Yu-Li; Fang, Chiu-Ping; Liu, Chia-Chen; Sun, Chung-Ming

2017-04-10

Diversity-oriented synthesis of coumarin-linked benzimidazoles from N-(2-aminophenyl)-2-cyanoacetamide was achieved via a one-pot, three-step sequential reaction in excellent yields. In situ intramolecular cyclization of the cyanoacetamide afforded benzimidazoles which subsequently underwent a Knoevenagel condensation of the 2-cyanomethylbenzimidazoles with salicylaldehydes promoted by triethylamine to reach the target compounds. An important intermediate, 2-(2-imino-2H-chromen-3-yl)-1H-benzimidazole was characterized by X-ray analysis and further hydrolyzed to 2-(coumarin-3-yl)benzimidazole in acidic condition. Among the synthesized compounds, some were found to be promising inhibitors of porcine kidney d-amino acid oxidase (pkDAO).

Coumarins in horse chestnut flowers: isolation and quantification by UPLC method.

PubMed

Dudek-Makuch, Marlena; Matławska, Irena

2013-01-01

The coumarins: scopoletin, esculetin and fraxetin were isolated from the flowers of horse chestnut (Aesculus hippocastanum L., Hippocastanaceae) and identified by spectrophotometric methods (UV, 1H, 13C NMR, ESI-MS). Their content, determined using the Ultra Performance Liquid Chromatography (UPLC), was 0.41, 0.13 and 0.05%, respectively.

Preparation and characterization of mesoporous ZnO-ZrO2 doped by Cr, Nd and Dy as a catalyst for conversion of coumarin using ultrasensitive fluorometric method

NASA Astrophysics Data System (ADS)

Ibrahim, M. M.

2017-04-01

Doping of mesoporous ZnO-ZrO2 nanoparticles with transition metal and lanthanides (Cr, Nd, Dy) were used as a catalyst to develop an ultrasensitive fluorometric method for the conversion of non fluorescent coumarin to highly fluorescent 7-hydroxycoumarin using H2O2 or light. It was found that doped- ZnO-ZrO2 mixed oxide can catalyze the decomposition of H2O2 to produce •OH radicals, which in turn convert coumarin to 7-hydroxycoumarin. At contrast, the doping has deleterious effect on conversion of coumarin by light due to high band gap and high concentrations of doping increase the recombination rate of electron and holes. Doped mixed oxides prepared by impregnation method and characterized by studying their structural, surface and optical properties. Chromium doped ZnO-ZrO2 had the highest rate of formation of hydroxyl radical due to decomposition of H2O2 and therefore 7-hydroxycoumarin due to surface area, small crystal size and high redox potential.

Solvent as electron donor: Donor/acceptor electronic coupling is a dynamical variable

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

Castner, E.W. Jr.; Kennedy, D.; Cave, R.J.

2000-04-06

The authors combine analysis of measurements by femtosecond optical spectroscopy, computer simulations, and the generalized Mulliken-Hush (GMH) theory in the study of electron-transfer reactions and electron donor-acceptor interactions. The study focus is on ultrafast photoinduced electron-transfer reactions from aromatic amine solvent donors to excited-state acceptors. The experimental results from femtosecond dynamical measurements fall into three categories: six coumarin acceptors reductively quenched by N,N-dimethylaniline (DMA), eight electron-donating amine solvents reductively quenching coumarin 152 (7-(dimethylamino)-4-(trifluoromethyl)-coumarin), and reductive quenching dynamics of two coumarins by DMA as a function of dilution in the nonreactive solvents toluene and chlorobenzene. Applying a combination of molecular dynamicsmore » trajectories, semiempirical quantum mechanical calculations (of the relevant adiabatic electronic states), and GMH theory to the C152/DMA photoreaction, the authors calculate the electron donor/acceptor interaction parameter H{sub DA} at various time frames, H{sub DA} is strongly modulated by both inner-sphere and outer-sphere nuclear dynamics, leading us to conclude that H{sub DA} must be considered as a dynamical variable.« less

A Self-Assembled Coumarin-Anchored Dendrimer for Efficient Gene Delivery and Light-Responsive Drug Delivery.

PubMed

Wang, Hui; Miao, Wujun; Wang, Fei; Cheng, Yiyun

2018-06-11

The assembly of low molecular weight polymers into highly efficient and nontoxic nanostructures has broad applicability in gene delivery. In this study, we reported the assembly of coumarin-anchored low generation dendrimers in aqueous solution via hydrophobic interactions. The synthesized material showed significantly improved DNA binding and gene delivery, and minimal toxicity on the transfected cells. Moreover, the coumarin moieties in the assembled nanostructures endow the materials with light-responsive drug delivery behaviors. The coumarin substitutes in the assembled nanostructures were cross-linked with each other upon irradiation at 365 nm, and the cross-linked assemblies were degraded upon further irradiation at 254 nm. As a result, the drug-loaded nanoparticle showed a light-responsive drug release behavior and light-enhanced anticancer activity. The assembled nanoparticle also exhibited a complementary anticancer activity through the codelivery of 5-fluorouracil and a therapeutic gene encoding tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). This study provided a facile strategy to develop light-responsive polymers for the codelivery of therapeutic genes and anticancer drugs.

Lanthanide and transition metal complexes of bioactive coumarins: molecular modeling and spectroscopic studies.

PubMed

Georgieva, I; Mihaylov, Tz; Trendafilova, N

2014-06-01

The present paper summarizes theoretical and spectroscopic investigations on a series of active coumarins and their lanthanide and transition metal complexes with application in medicine and pharmacy. Molecular modeling as well as IR, Raman, NMR and electronic spectral simulations at different levels of theory were performed to obtain important molecular descriptors: total energy, formation energy, binding energy, stability, conformations, structural parameters, electron density distribution, molecular electrostatic potential, Fukui functions, atomic charges, and reactive indexes. The computations are performed both in gas phase and in solution with consideration of the solvent effect on the molecular structural and energetic parameters. The investigations have shown that the advanced computational methods are reliable for prediction of the metal-coumarin binding mode, electron density distribution, thermodynamic properties as well as the strength and nature of the metal-coumarin interaction (not experimentally accessible) and correctly interpret the experimental spectroscopic data. Known results from biological tests for cytotoxic, antimicrobial, anti-fungal, spasmolytic and anti-HIV activities on the studied metal complexes are reported and discussed. Copyright © 2014 Elsevier Inc. All rights reserved.

Recent developments of coumarin-containing derivatives and their anti-tubercular activity.

PubMed

Hu, Yuan-Qiang; Xu, Zhi; Zhang, Shu; Wu, Xiang; Ding, Jun-Wei; Lv, Zao-Sheng; Feng, Lian-Shun

2017-08-18

Tuberculosis (TB) is a lift-threatening chronic deadliest infectious disease caused predominantly by Mycobacterium tuberculosis (MTB) which affects primarily the lungs (pulmonary TB) apart from other vital organs. The emergence of drug-resistant TB (DR-TB), multidrug-resistant TB (MDR-TB), extensively drug-resistant TB (XDR-TB) and the recently cases of totally drug resistant (TDR) towards currently accessible standard drugs was increased up to alarming level in the recent decades. In pursuit of searching new anti-TB agents, numerous of derivatives have been synthesized and screened for their anti-TB activity. Coumarins are one of the most important classes of natural products that exhibited various biological activities, and their derivatives regarded as a new class of effective anti-TB candidates owing to their potential anti-TB activity. Thus, coumarin skeleton has attracted great interest in the development of new anti-TB agents. This review outlines the advances in the application of coumarin-containing derivatives as anti-TB agents and the critical aspects of design and structure-activity relationship of these derivatives. Published by Elsevier Masson SAS.

Anti-mitotic potential of 7-diethylamino-3(2 Prime -benzoxazolyl)-coumarin in 5-fluorouracil-resistant human gastric cancer cell line SNU620/5-FU

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

Kim, Nam Hyun; Kim, Su-Nam; Oh, Joa Sub

2012-02-24

Highlights: Black-Right-Pointing-Pointer DBC exerts antiproliferative potential against 5FU-resistant human gastric cancer cells. Black-Right-Pointing-Pointer This effect is mediated by destabilization of microtubules and subsequent mitotic arrest. Black-Right-Pointing-Pointer DBC enhances apoptosis via caspase activation and downregulation of antiapoptotic genes. -- Abstract: In this study, we investigate an anti-mitotic potential of the novel synthetic coumarin-based compound, 7-diethylamino-3(2 Prime -benzoxazolyl)-coumarin, in 5-fluorouracil-resistant human gastric cancer cell line SNU-620-5FU and its parental cell SNU-620. It exerts the anti-proliferative effects with similar potencies against both cancer cells, which is mediated by destabilization of microtubules and subsequent mitotic arrest. Furthermore, this compound enhances caspase-dependent apoptotic cell deathmore » via decreased expression of anti-apoptotic genes. Taken together, our data strongly support anti-mitotic potential of 7-diethylamino-3(2 Prime -benzoxazolyl)-coumarin against drug-resistant cancer cells which will prompt us to further develop as a novel microtubule inhibitor for drug-resistant cancer chemotherapy.« less

Photoreversible Covalent Hydrogels for Soft-Matter Additive Manufacturing.

PubMed

Kabb, Christopher P; O'Bryan, Christopher S; Deng, Christopher C; Angelini, Thomas E; Sumerlin, Brent S

2018-05-16

Reversible covalent chemistry provides access to robust materials with the ability to be degraded and reformed upon exposure to an appropriate stimulus. Photoresponsive units are attractive for this purpose, as the spatial and temporal application of light is easily controlled. Coumarin derivatives undergo a [2 + 2] cycloaddition upon exposure to long-wave UV irradiation (365 nm), and this process can be reversed using short-wave UV light (254 nm). Therefore, polymers cross-linked by coumarin groups are excellent candidates as reversible covalent gels. In this work, copolymerization of coumarin-containing monomers with the hydrophilic comonomer N, N-dimethylacrylamide yielded water-soluble, linear polymers that could be cured with long-wave UV light into free-standing hydrogels, even in the absence of a photoinitiator. Importantly, the gels were reverted back to soluble copolymers upon short-wave UV irradiation. This process could be cycled, allowing for recycling and remolding of the hydrogel into additional shapes. Further, this hydrogel can be imprinted with patterns through a mask-based, post-gelation photoetching method. Traditional limitations of this technique, such as the requirement for uniform etching in one direction, have been overcome by combining these materials with a soft-matter additive manufacturing methodology. In a representative application of this approach, we printed solid structures in which the interior coumarin-cross-linked gel is surrounded by a nondegradable gel. Upon exposure to short-wave UV irradiation, the coumarin-cross-linked gel was reverted to soluble prepolymers that were washed away to yield hollow hydrogel objects.

Inhibitory effects and structural insights for a novel series of coumarin-based compounds that selectively target human CA IX and CA XII carbonic anhydrases.

PubMed

De Luca, Laura; Mancuso, Francesca; Ferro, Stefania; Buemi, Maria Rosa; Angeli, Andrea; Del Prete, Sonia; Capasso, Clemente; Supuran, Claudiu T; Gitto, Rosaria

2018-01-01

Coumarin derivatives are a peculiar class of inhibitors of the family of metalloenzymes carbonic anhydrases (CA, EC 4.2.1.1). Several coumarins display higher affinity and selectivity toward most relevant and druggable CA isoforms. By decorating the natural compound umbelliferone (1) we have identified a new series of coumarin-based compounds demonstrating high CA inhibitory effects with nanomolar affinity for hCA IX and hCA XII isoforms that were considered a target amenable to develop antitumor agents. The most active tested compounds proved to be potent inhibitors with K i values equal to that of the well-known inhibitor acetazolamide (AAZ), that lacks selectivity over ubiquitous hCA I and hCA II. As suggested by docking studies the coumarins, that are lacking of the canonical metal binding groups, do not interact with Zinc ion within the catalytic site as found for classical sulfonamide type inhibitors of CAs. Thus, the studied inhibitors might possess a non-classical inhibitory mode of action preventing the carbon dioxide to entry into catalytic cavity and its conversion into bicarbonate ion. Specifically, the most active inhibitor of hCA XII compound 18i (K i value of 5.5 nM) and its supposed hydrolytic products could establish a web of H-bond interactions within the enzymatic cavity. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Amelioration of L-thyroxine-induced hyperthyroidism by coumarin (1,2-benzopyrone) in female rats.

PubMed

Panda, Sunanda; Kar, Anand

2007-11-01

1. The efficacy of coumarin (1,2-benzopyrone) was examined for the regulation of hyperthyroidism in female rats. 2. Coumarin was administered (10 mg/kg per day for 15 days) to l-thyroxine (L-T(4))-induced hyperthyroid as well as to euthyroid rats and changes in serum concentrations of thyroid hormones and in associated parameters, such as serum cholesterol, activity of hepatic 5'-monodeiodinase (5'DI) and glucose-6-phosphatase (G-6-Pase), glycogen content, bodyweight and daily food consumption, were analysed. Simultaneously, changes in hepatic lipid peroxidation (LPO), reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were also investigated. 3. Although L-T(4) administration increased serum levels of thyroid hormones, the activity of hepatic 5'DI, G-6-Pase and LPO and daily food consumption, it decreased the level of serum cholesterol, hepatic glycogen content and the activities of anti-oxidant enzymes, such as SOD, CAT and GSH. 4. However, simultaneous administration of coumarin for 15 days to a group of hyperthyroid animals reversed most of the aforementioned changes, indicating its potential to ameliorate hyperthyroidism. Moreover, the drug did not increase, but rather decreased, hepatic LPO, suggesting its safe nature. 5. The present findings reveal a positive role for coumarin in the regulation of hyperthyroidism without any hepatotoxicity. It also appears that the test compound inhibits thyroid function at both a glandular level and at the level of peripheral conversion of T(4) to tri-iodothyronine.

Pathological and biochemical evaluation of coumarin and chlorophyllin against aflatoxicosis in rat.

PubMed

Abdel-Latif, Mohamed S; Elmeleigy, Khaled M; Aly, Tahany A A; Khattab, Marwa S; Mohamed, Sara M

2017-06-14

Aflatoxin contamination of animal diet has adverse effects on animal health and productivity. This study was performed to investigate the effect of using coumarin and/or chlorophyllin in rat diet against aflatoxicosis. Fifty-four rats were assigned into 7 groups (6 rats each). G1 was a negative control. G2 received water with coumarin 0.5%. G3 received water with chlorophyllin 0.5%. G4 received water with coumarin 0.5% and chlorophyllin 0.5%. G5-8 fed aflatoxin B 1 1000ppb in diet. Group 6-8 were administered similar treatments as G2-4. The experiment ended after 8 weeks. Random glucose, total lipid, total cholesterol, total triglycerides, total protein, serum ALT, AST, creatinine, and urea were measured. Histopathology of liver, kidney and pancreas and immunohistochemical staining of placental glutathione-S-transferase (GST-P) in liver were performed. The glucose serum level, cholesterol, AST, and ALT were elevated in G5 compared to G6-8. The liver and kidney lesions in G5 included vacuolation and necrosis which subsided in G6-8. The necrosis and inflammatory cells infiltration in the pancreas of G5 were absent in G6-8. GST-P positive hepatocytes were abundant in G5, few in G6 and absent in G7 and G8. In conclusion, the chlorophyllin and coumarin possessed protective and anti-carcinogenic effect against aflatoxicosis in rats. Copyright © 2017 Elsevier GmbH. All rights reserved.

Oviposition Deterrent Activities of Pachyrhizus erosus Seed Extract and Other Natural Products on Plutella xylostella (Lepidoptera: Plutellidae)

PubMed Central

Basukriadi, Adi; Wilkins, Richard M.

2014-01-01

Abstract An extract of a rotenone-containing plant yam bean, Pachyrhizus erosus (L.) Urban, seeds was tested against the diamondback moth, Plutella xylostella (L.) in a greenhouse to determine its potential as an oviposition deterrent and compared with coumarin and rutin, known as diamondback moth oviposition deterrent compounds, rotenone, and an extract of Peruvian cube root, at a concentration of 0.5% (w/v). Oviposition deterrent index (ODI) was used to determine effects of extracts or compounds in inhibiting oviposition of diamondback moth. Coumarin showed a stronger deterrent effect than the yam bean seed extract with a higher ODI value. On the contrary, rotenone, rutin, and the cube root extract, containing 6.7% (w/w) of rotenone, showed no significant deterrent effects having low or negative ODI values, suggesting that the deterrent effect of the yam bean seed extract is not due to rotenone content of the yam bean seeds. The extract of yam bean seed and coumarin partially deterred the moth from laying eggs on treated leaves in a concentration-dependent manner. The effective concentration for 50% deterrency of coumarin and the yam bean seed extract were 0.11 and 0.83% (w/v), respectively. However, the yam bean seed extract showed a residual deterrent effect on the moth even at 3 d after the treatment and is probably because of its low volatile nature. A long-term deterrency of the yam bean seed extract is an advantage over coumarins. Both the yam bean seed extract and coumarin deterred diamondback moth from laying eggs in total darkness, indicating their nonvisual deterrent effect. This made the extract an effective deterrence to diamondback moth in light and in darkness. To conclude, this study revealed the potential of the crude extract of the yam bean seed to prevent diamondback moth from ovipositing on its plant host. PMID:25525107

Oviposition deterrent activities of Pachyrhizus erosus seed extract and other natural products on Plutella xylostella (Lepidoptera: Plutellidae).

PubMed

Basukriadi, Adi; Wilkins, Richard M

2014-01-01

An extract of a rotenone-containing plant yam bean, Pachyrhizus erosus (L.) Urban, seeds was tested against the diamondback moth, Plutella xylostella (L.) in a greenhouse to determine its potential as an oviposition deterrent and compared with coumarin and rutin, known as diamondback moth oviposition deterrent compounds, rotenone, and an extract of Peruvian cube root, at a concentration of 0.5% (w/v). Oviposition deterrent index (ODI) was used to determine effects of extracts or compounds in inhibiting oviposition of diamondback moth. Coumarin showed a stronger deterrent effect than the yam bean seed extract with a higher ODI value. On the contrary, rotenone, rutin, and the cube root extract, containing 6.7% (w/w) of rotenone, showed no significant deterrent effects having low or negative ODI values, suggesting that the deterrent effect of the yam bean seed extract is not due to rotenone content of the yam bean seeds. The extract of yam bean seed and coumarin partially deterred the moth from laying eggs on treated leaves in a concentration-dependent manner. The effective concentration for 50% deterrency of coumarin and the yam bean seed extract were 0.11 and 0.83% (w/v), respectively. However, the yam bean seed extract showed a residual deterrent effect on the moth even at 3 d after the treatment and is probably because of its low volatile nature. A long-term deterrency of the yam bean seed extract is an advantage over coumarins. Both the yam bean seed extract and coumarin deterred diamondback moth from laying eggs in total darkness, indicating their nonvisual deterrent effect. This made the extract an effective deterrence to diamondback moth in light and in darkness. To conclude, this study revealed the potential of the crude extract of the yam bean seed to prevent diamondback moth from ovipositing on its plant host. © The Author 2014. Published by Oxford University Press on behalf of the Entomological Society of America.

Cloning, Functional Characterization and Site-Directed Mutagenesis of 4-Coumarate: Coenzyme A Ligase (4CL) Involved in Coumarin Biosynthesis in Peucedanum praeruptorum Dunn

PubMed Central

Liu, Tingting; Yao, Ruolan; Zhao, Yucheng; Xu, Sheng; Huang, Chuanlong; Luo, Jun; Kong, Lingyi

2017-01-01

Coumarins are the main bioactive compounds in Peucedanum praeruptorum Dunn, a common Chinese herbal medicine. Nevertheless, the genes involved in the biosynthesis of core structure of coumarin in P. praeruptorum have not been identified yet. 4-Coumarate: CoA ligase (4CL) catalyzes the formation of hydroxycinnamates CoA esters, and plays an essential role at the divergence point from general phenylpropanoid metabolism to major branch pathway of coumarin. Here, three novel putative 4CL genes (Pp4CL1, Pp4CL7, and Pp4CL10) were isolated from P. praeruptorum. Biochemical characterization of the recombinant proteins revealed that Pp4CL1 utilized p-coumaric and ferulic acids as its two main substrates for coumarin biosynthesis in P. praeruptorum. Furthermore, Pp4CL1 also exhibited activity toward caffeic, cinnamic, isoferulic, and o-coumaric acids and represented a bona fide 4CL. Pp4CL7 and Pp4CL10 had no catalytic activity toward hydroxycinnamic acid compounds. But they had close phylogenetic relationship to true 4CLs and were defined as 4CL-like genes. Among all putative 4CLs, Pp4CL1 was the most highly expressed gene in roots, and its expression level was significantly up-regulated in mature roots compared with seedlings. Subcellular localization studies showed that Pp4CL1 and Pp4CL10 proteins were localized in the cytosol. In addition, site-directed mutagenesis of Pp4CL1 demonstrated that amino acids of Tyr-239, Ala-243, Met-306, Ala-309, Gly-334, Lys-441, Gln-446, and Lys-526 were essential for substrate binding or catalytic activities. The characterization and site-directed mutagenesis studies of Pp4CL1 lays a solid foundation for elucidating the biosynthetic mechanisms of coumarins in P. praeruptorum and provides further insights in understanding the structure–function relationships of this important family of proteins. PMID:28144249

Co-sensitization of ruthenium(II) dye-sensitized solar cells by coumarin based dyes

NASA Astrophysics Data System (ADS)

Athanas, Anish Babu; Thangaraj, Shankar; Kalaiyar, Swarnalatha

2018-05-01

Co-sensitization technique has been appraised for attaining enhanced performance in dye-sensitized solar cells (DSSCs). DSSCs are fabricated with a heteroleptic Ru(II) sensitizer (RDAB1) containing 4,4‧-diamino-2,2‧-bipyridine (dabpy) ligand, co-sensitized with electron donor-acceptor type coumarin containing thiophene (CT) and indole (CI) moieties. The individual overall power conversion efficiency of the sensitizer is 5.44%. Enhanced power conversion efficiencies of 6.34% and 7.09% were observed when RDAB1 was co-sensitized with Coumarin containing CI and CT respectively. The enhanced PCE can be attributed to the presence of co-sensitizers which effectively overcome the light absorption by I-/I3-, dye aggregation and charge recombination.

The design, synthesis, and evaluation of coumarin ring derivatives of the novobiocin scaffold that exhibit antiproliferative activity.

PubMed

Donnelly, Alison C; Mays, Jared R; Burlison, Joseph A; Nelson, John T; Vielhauer, George; Holzbeierlein, Jeffrey; Blagg, Brian S J

2008-11-21

Novobiocin, a known DNA gyrase inhibitor, binds to a nucleotide-binding site located on the Hsp90 C-terminus and induces degradation of Hsp90-dependent client proteins at approximately 700 microM in breast cancer cells (SKBr3). Although many analogues of novobiocin have been synthesized, it was only recently demonstrated that monomeric species exhibit antiproliferative activity against various cancer cell lines. To further refine the essential elements of the coumarin core, a series of modified coumarin derivatives was synthesized and evaluated to elucidate structure-activity relationships for novobiocin as an anticancer agent. Results obtained from these studies have produced novobiocin analogues that manifest low micromolar activity against several cancer cell lines.

Coumarin-BODIPY hybrids by heteroatom linkage: versatile, tunable and photostable dye lasers for UV irradiation.

PubMed

Esnal, I; Duran-Sampedro, G; Agarrabeitia, A R; Bañuelos, J; García-Moreno, I; Macías, M A; Peña-Cabrera, E; López-Arbeloa, I; de la Moya, S; Ortiz, M J

2015-03-28

Linking amino and hydroxycoumarins to BODIPYs through the amino or hydroxyl group lets the easy construction of unprecedented photostable coumarin-BODIPY hybrids with broadened and enhanced absorption in the UV spectral region, and outstanding wavelength-tunable laser action within the green-to-red spectral region (∼520-680 nm). These laser dyes allow the generation of a valuable tunable UV (∼260-350 nm) laser source by frequency doubling, which is essential to study accurately the photochemistry of biological molecules under solar irradiation. The tunability is achieved by selecting the substitution pattern of the hybrid. Key factors are the linking heteroatom (nitrogen vs. oxygen), the number of coumarin units joined to the BODIPY framework and the involved linking positions.

Anti-inflammatory and antimicrobial coumarins from the stems of Eurya chinensis.

PubMed

Song, Jia-Ling; Yuan, Yao; Tan, Hai-Bo; Huang, Ri-Ming; Liu, Hong-Xin; Xu, Zhi-Fang; Qiu, Sheng-Xiang

2017-03-01

Two new coumarins, named (±)-euryacoumarin A (1) and 6-demethylobtusinin (2), and one new natural coumarin, named euryacoumarin B (3), along with two known compounds, scopoletin (4) and obtusinol (5), were isolated from the stems of Eurya chinensis. Their structures were elucidated by means of extensive spectroscopic methods and comparison with data reported in the literatures. Compound 1 exhibited significant inhibition of LPS-induced nitric oxide (NO) production in RAW264.7 cells with IC 50 value of 35.64 ± 1.73 μM, and showed marginal antibacterial activities against Bacillus subtilis and B. cereus with MIC values of 50.59 ± 2.12 and 35.42 ± 0.96 μM, respectively.

Optical gain characteristics of C 460 and C 450.

PubMed

Sharma, Vijay K; Sahare, P D; Pandey, A; Mohan, D

2003-03-15

Dye concentration dependent gain spectra for Coumarin 460 (C 460) and Coumarin 450 (C 450) in ethanol have been studied using Amplified Spontaneous Emission (ASE) technique under Nitrogen laser (337.1 nm) excitation in the concentration range 10(-2)-10(-5) m/l. The dependence of lasing wavelength and peak gain on concentration have been understood in terms of variation of fluorescence lifetime, which is due to photo-physical processes such as radiation trapping and concentration-quenching. Pump intensity dependence of efficiency is also explained in terms of fluorescence lifetime. A comparison of the stability of the two dyes has also been made on the basis of the functional groups at different positions of the basic coumarin. Copyright 2002 Elsevier Science B.V.

Atropisomerisation in sterically hindered α,β-disubstituted cyclopentenones derived from an intermolecular cobalt(0)-mediated Pauson-Khand reaction.

PubMed

Moulton, Benjamin E; Lynam, Jason M; Duhme-Klair, Anne-Kathrin; Zheng, Wenxu; Lin, Zhenyang; Fairlamb, Ian J S

2010-12-07

4-(2-Phenylethynyl)-2H-chromen-2-one reacts with norbornene and Co(2)(CO)(8) in an intermolecular Pauson-Khand reaction by focused microwave dielectric heating. Two regioisomeric products are formed; the electron-deficient coumarin moiety preferentially occupies the β-position of the cyclopentenone ring system, whereas the phenyl occupies the α-position. The sterically hindered α,β-(2,3)-disubstituted cyclopentenone regioisomeric products exhibit pronounced atropisomerisation, and the magnitude of the energetic barrier to interconversion between these atropisomers is dependent on the relative position of the coumarin moieties. Interconversion is slow when the coumarin is found in the α-position, whereas interconversion is relatively fast when found in the β-position.

Flavonoids, Phenolic Acids and Coumarins from the Roots of Althaea officinalis.

PubMed

Gudej, J

1991-06-01

From the roots of ALTHAEA OFFICINALIS two flavonoid glycosides were separated. Phenolic acids and coumarins were investigated chromatographically. The structures of the compounds were established on the basis of acid hydrolysis and spectroscopic methods (UV, (1)H-NMR, (13)C-NMR) as hypolaetin 8-glucoside and the new flavonoid sulphate - isoscutellarein 4'-methyl ether 8-glucoside-2''-SO (3)K.

Insights into structure–activity relationship of GABAA receptor modulating coumarins and furanocoumarins

PubMed Central

Singhuber, Judith; Baburin, Igor; Ecker, Gerhard F.; Kopp, Brigitte; Hering, Steffen

2011-01-01

The coumarins imperatorin and osthole are known to exert anticonvulsant activity. We have therefore analyzed the modulation of GABA-induced chloride currents (IGABA) by a selection of 18 coumarin derivatives on recombinant α1β2γ2S GABAA receptors expressed in Xenopus laevis oocytes by means of the two-microelectrode voltage clamp technique. Osthole (EC50=14±1 μM) and oxypeucedanin (EC50=25±8 μM) displayed the highest efficiency with IGABA potentiation of 116±4% and 547±56%, respectively. IGABA enhancement by osthole and oxypeucedanin was not inhibited by flumazenil (1 μM) indicating an interaction with a binding site distinct from the benzodiazepine binding site. In general, prenyl residues are essential for the positive modulatory activity, while longer side chains or bulkier residues (e.g. geranyl residues) diminish IGABA modulation. Generation of a binary classification tree revealed the importance of polarisability, which is sufficient to distinguish actives from inactives. A 4-point pharmacophore model based on oxypeucedanin – comprising three hydrophobic and one aromatic feature – identified 6 out of 7 actives as hits. In summary, (oxy-)prenylated coumarin derivatives from natural origin represent new GABAA receptor modulators. PMID:21749864

Syntheses of coumarin-tacrine hybrids as dual-site acetylcholinesterase inhibitors and their activity against butylcholinesterase, Aβ aggregation, and β-secretase.

PubMed

Sun, Qi; Peng, Da-Yong; Yang, Sheng-Gang; Zhu, Xiao-Lei; Yang, Wen-Chao; Yang, Guang-Fu

2014-09-01

Exploring small-molecule acetylcholinesterase (AChE) inhibitors to slow the breakdown of acetylcholine (Ach) represents the mainstream direction for Alzheimer's disease (AD) therapy. As the first acetylcholinesterase inhibitor approved for the clinical treatment of AD, tacrine has been widely used as a pharmacophore to design hybrid compounds in order to combine its potent AChE inhibition with other multi-target profiles. In present study, a series of novel tacrine-coumarin hybrids were designed, synthesized and evaluated as potent dual-site AChE inhibitors. Moreover, compound 1g was identified as the most potent candidate with about 2-fold higher potency (Ki=16.7nM) against human AChE and about 2-fold lower potency (Ki=16.1nM) against BChE than tacrine (Ki=35.7nM for AChE, Ki=8.7nM for BChE), respectively. In addition, some of the tacrine-coumarin hybrids showed simultaneous inhibitory effects against both Aβ aggregation and β-secretase. We therefore conclude that tacrine-coumarin hybrid is an interesting multifunctional lead for the AD drug discovery. Copyright © 2014 Elsevier Ltd. All rights reserved.

Fluorescence labeling of carbonylated lipids and proteins in cells using coumarin-hydrazide

PubMed Central

Vemula, Venukumar; Ni, Zhixu; Fedorova, Maria

2015-01-01

Carbonylation is a generic term which refers to reactive carbonyl groups present in biomolecules due to oxidative reactions induced by reactive oxygen species. Carbonylated proteins, lipids and nucleic acids have been intensively studied and often associated with onset or progression of oxidative stress related disorders. In order to reveal underlying carbonylation pathways and biological relevance, it is crucial to study their intracellular formation and spatial distribution. Carbonylated species are usually identified and quantified in cell lysates and body fluids after derivatization using specific chemical probes. However, spatial cellular and tissue distribution have been less often investigated. Here, we report coumarin-hydrazide, a fluorescent chemical probe for time- and cost-efficient labeling of cellular carbonyls followed by fluorescence microscopy to evaluate their intracellular formation both in time and space. The specificity of coumarin-hydrazide was confirmed in time- and dose-dependent experiments using human primary fibroblasts stressed with paraquat and compared with conventional DNPH-based immunocytochemistry. Both techniques stained carbonylated species accumulated in cytoplasm with strong perinuclear clustering. Using a complimentary array of analytical methods specificity of coumarin-hydrazide probe towards both protein- and lipid-bound carbonyls has been shown. Additionally, co-distribution of carbonylated species and oxidized phospholipids was demonstrated. PMID:25974625

Melanogenesis stimulation in murine b16 melanoma cells by umberiferae plant extracts and their coumarin constituents.

PubMed

Matsuda, Hideaki; Hirata, Noriko; Kawaguchi, Yoshiko; Yamazaki, Miho; Naruto, Shunsuke; Shibano, Makio; Taniguchi, Masahiko; Baba, Kimiye; Kubo, Michinori

2005-07-01

Melanogenesis stimulation activities of seven ethanolic extracts obtained from Umbelliferae plants used as Chinese crude drugs, namely the roots of Angelica dahurica BENTH. et HOOK., A. biserrata SHEN et YUAN, Notopterygium incisum TING, Heracleum lanatum MICHX., and H. candicans WALL., and the fruits of Cinidium monnieri (L.) CUSSON and C. formosanum YABE, were examined by using cultured murine B16 melanoma cells. Among them, the extract (5, 25 microg/ml) of H. lanatum showed a potent stimulatory effect on melanogenesis with significant enhancement of cell proliferation in a dose-dependent manner. The melanogenesis stimulatory effects of sixteen coumarins (1-16) isolated from the seven Umbelliferae crude drugs were also examined. Among them, linear-furocoumarins [psoralen (1), xanthotoxin (2), bergapten (3), and isopimpinellin (4)] and angular-furocoumarin [sphondin (13)] exhibited potent melanogenesis stimulation activity. From the view point of structure-activity relationships, it may be assumed that a linear-furocoumarin ring having a hydrogen and/or methoxyl group at 5 and 8 positions such as 1, 2, 3 and 4 was preferable for the melanogenesis stimulation activity. The introduction of a prenyl group into the furocoumarin ring was disadvantageous. Coumarin derivatives having a simple coumarin ring were inactive.

Preferred Molecular Orientation of Coumarin 343 on TiO 2 Surfaces: Application to Dye-Sensitized Solar Cells

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

McCree-Grey, Jonathan; Cole, Jacqueline M.; Evans, Peter J.

2015-07-21

The dye…TiO2 interfacial structure in working electrodes of dye-sensitized solar cells (DSCs) is known to influence its photovoltaic device performance. Despite this, direct and quantitative reports of such structure remain sparse. This case study presents the application of X-ray reflectometry to determine the preferred structural orientation and molecular packing of the organic dye, coumarin 343, adsorbed onto amorphous TiO2. Results show that the dye molecules are, on average, tilted by 61.1° relative to the TiO2 surface, and are separated from each other by 8.2 Å. These findings emulate the molecular packing arrangement of a monolayer of coumarin 343 within itsmore » crystal structure. This suggests that the dye adsorbs onto TiO2 in one of its lowest energy configurations, i.e. dye…TiO2 self assembly is driven more by thermodynamic rather than kinetic means. Complementary DSC device tests illustrate that this interfacial structure compromises photovoltaic performance, unless a suitably sized co-adsorbant is interdispersed between the coumarin 343 chromophores on the TiO2 surface.« less

Mobilization of Iron by Plant-Borne Coumarins.

PubMed

Tsai, Huei Hsuan; Schmidt, Wolfgang

2017-06-01

Iron is one of the most abundant elements in soils, but its low phytoavailability at high pH restricts plant communities on alkaline soils to taxa that have evolved efficient strategies to increase iron solubility. Recent evidence provides support for a previously underestimated role of root-secreted coumarins in mobilizing iron through reduction and chelation as part of an orchestrated strategy evolved to improve the acquisition of iron from recalcitrant pools. Understanding the mechanisms that tune the production of iron-mobilizing coumarins and their intricate interplay with other biosynthesis pathways could yield clues for deciphering the molecular basis of 'iron efficiency' - the ability of plants to thrive on soils with limited iron availability - and may open avenues for generating iron-fortified crops. Copyright © 2017 Elsevier Ltd. All rights reserved.

Tetrapeptide-coumarin conjugate 3D networks based on hydrogen-bonded charge transfer complexes: gel formation and dye release.

PubMed

Guo, Zongxia; Gong, Ruiying; Jiang, Yi; Wan, Xiaobo

2015-08-14

Oligopeptide-based derivatives are important synthons for bio-based functional materials. In this article, a Gly-(L-Val)-Gly-(L-Val)-coumarin (GVGV-Cou) conjugate was synthesized, which forms 3D networks in ethanol. The gel nanostructures were characterized by UV-vis spectroscopy, FT-IR spectroscopy, X-ray diffraction (XRD), SEM and TEM. It is suggested that the formation of charge transfer (CT) complexes between the coumarin moieties is the main driving force for the gel formation. The capability of the gel to encapsulate and release dyes was explored. Both Congo Red (CR) and Methylene Blue (MB) can be trapped in the CT gel matrix and released over time. The present gel might be used as a functional soft material for guest encapsulation and release.

Single-molecule detection by two-photon excitation of fluorescence

NASA Astrophysics Data System (ADS)

Zander, Christoph; Brand, Leif; Eggeling, C.; Drexhage, Karl-Heinz; Seidel, Claus A. M.

1997-05-01

Using a mode-locked titanium: sapphire laser at 700 nm for two-photon excitation we studied fluorescence bursts from individual coumarin 120 molecules in water and triacetin. Fluorescence lifetimes and multichannel scaler traces have been measured simultaneously. Due to the fact that scattered excitation light as well as Raman scattered photons can be suppressed by a short-pass filter a very low background level was achieved. To identify the fluorophore by its characteristic fluorescence lifetime the time-resolved fluorescence signals were analyzed by a maximum likelihood estimator. The obtained average fluorescence lifetimes (tau) av equals 4.8 +/- 1.2 ns for coumarin 120 in water and (tau) av equals 3.3 +/- 0.6 for coumarin 120 in triacetin are in good agreement with results obtained from separate measurements at higher concentrations.

Novel fluorescent pH sensor based on coumarin with piperazine and imidazole substituents.

PubMed

Saleh, Na'il; Al-Soud, Yaseen A; Nau, Werner M

2008-12-01

A new coumarin derivative containing piperazine and imidazole moieties is reported as a fluorophore for hydrogen ions sensing. The fluorescence enhancement of the studied sensor with an increase in hydrogen ions concentration is based on the hindering of photoinduced electron transfer from the piperazinyl amine and the imidazolyl amine to the coumarin fluorophore by protonation. The presented sensor has a novel design of fluorophore-spacer-receptor(1)-receptor(2) format, which is proposed to sense two ranges of pH (from 2.5 to 5.5) and (from 10 to 12) instead of sensing one pH range. A model compound, in which the piperazinyl ring is absent, was synthesized as well to confirm the novel pH sensing of the proposed sensor.

The Design, Synthesis and Evaluation of Coumarin Ring Derivatives of the Novobiocin Scaffold that Exhibit Anti-proliferative Activity

PubMed Central

Donnelly, Alison C.; Mays, Jared R.; Burlison, Joseph A.; Nelson, John T.; Vielhauer, George; Holzbeierlein, Jeffrey; Blagg, Brian S. J.

2009-01-01

Novobiocin, a known DNA gyrase inhibitor, binds to a nucleotide-binding site located on the C-terminus of Hsp90 and induces degradation of Hsp90-dependent client proteins at ~700 μM in breast cancer cells (SkBr3). Although many analogues of novobiocin have been synthesized, it was only recently demonstrated that monomeric species can exhibit anti-proliferative activity against various cancer cell lines. To further refine the essential elements of the coumarin core, a series of modified coumarin derivatives was synthesized and evaluated for elucidation of structure–activity relationships for novobiocin as an anti-cancer agent. Results obtained from these studies have produced novobiocin analogues that manifest low micromolar activity against several cancer cell lines. PMID:18939877

Biotransformations with plant tissue cultures.

PubMed

Carew, D P; Bainbridge, T

1976-01-01

Suspension cultures of Catharanthus roseus, Apocynum cannabinum and Conium maculatum were examined for their capacity to transform aniline, anisole, acetanilide, benzoic acid and coumarin. None of the cultures transformed acetanilide but each produced acetanilide when fed aniline. All three cultures converted benzoic acid to its para-hydroxy derivative. Coumarin was selectively hydroxylated at the 7-position by Catharanthus and Conium and anisole was O-demethylated only by older Catharanthus tissue.

Simultaneous determination of aegeline and six coumarins from different parts of the plant Aegle marmelos using UHPLC-PDA-MS and chiral separation of aegeline using HPLC-ToF-MS

USDA-ARS?s Scientific Manuscript database

A fast UHPLC-PDA method was developed for the simultaneous analysis of one alkaloid, aegeline, and six coumarins namely: umbelliferone; scopoletin; marmesinin; 8-hydroxypsoralen angelicin and marmelosin from leaf, fruit, root and bark of Aegle marmelos (L.) Corrêa (Rutaceae). The method was validate...

Osthole activates glucose uptake but blocks full activation in L929 fibroblast cells, and inhibits uptake in HCLE cells

PubMed Central

Alabi, Ola D.; Gunnink, Stephen M.; Kuiper, Benjamin D.; Kerk, Samuel A.; Braun, Emily; Louters, Larry L.

2016-01-01

Aims Osthole, a coumarin derivative, has been used in Chinese medicine and studies have suggested a potential use in treatment of diabetes and cancers. Therefore, we investigated the effects of osthole and other coumarins on GLUT1 activity in two cell lines that exclusively express GLUT1. Main Methods We measured the magnitude and time frame of the effects of osthole and related coumarins on glucose uptake in two cells lines; L929 fibroblast cells which have low GLUT1 expression levels and low basal glucose uptake and HCLE cells which have high GLUT1 concentrations and high basal uptake. We also explored the effects of these coumarins in combination with other GLUT1 activators. Key findings Osthole activates glucose uptake in L929 cells with a modest maximum 1.7-fold activation achieved by 50 µM with both activation and recovery occurring within minutes. However, osthole blocks full acute activation of glucose uptake by other, more robust activators. This behavior mimics the effects of other thiol reactive compounds and suggests that osthole is interacting with cysteine residues, possibly within GLUT1 itself. Coumarin, 7-hydroxycoumarin, and 7-methoxycoumarin, do not affect glucose uptake, which is consistent with the notion that the isoprenoid structure in osthole may be important to gain membrane access to GLUT1. In contrast to its effects in L929 cells, osthole inhibits basal glucose uptake in the more active HCLE cells. Significance The differential effects of osthole in L929 and HCLE cells indicated that regulation of GLUT1 varies, likely depending on its membrane concentration. PMID:24657891

Osthole activates glucose uptake but blocks full activation in L929 fibroblast cells, and inhibits uptake in HCLE cells.

PubMed

Alabi, Ola D; Gunnink, Stephen M; Kuiper, Benjamin D; Kerk, Samuel A; Braun, Emily; Louters, Larry L

2014-05-02

Osthole, a coumarin derivative, has been used in Chinese medicine and studies have suggested a potential use in treatment of diabetes and cancers. Therefore, we investigated the effects of osthole and other coumarins on GLUT1 activity in two cell lines that exclusively express GLUT1. We measured the magnitude and time frame of the effects of osthole and related coumarins on glucose uptake in two cells lines; L929 fibroblast cells which have low GLUT1 expression levels and low basal glucose uptake and HCLE cells which have high GLUT1 concentrations and high basal uptake. We also explored the effects of these coumarins in combination with other GLUT1 activators. Osthole activates glucose uptake in L929 cells with a modest maximum 1.7-fold activation achieved by 50 μM with both activation and recovery occurring within minutes. However, osthole blocks full acute activation of glucose uptake by other, more robust activators. This behavior mimics the effects of other thiol reactive compounds and suggests that osthole is interacting with cysteine residues, possibly within GLUT1 itself. Coumarin, 7-hydroxycoumarin, and 7-methoxycoumarin, do not affect glucose uptake, which is consistent with the notion that the isoprenoid structure in osthole may be important to gain membrane access to GLUT1. In contrast to its effects in L929 cells, osthole inhibits basal glucose uptake in the more active HCLE cells. The differential effects of osthole in L929 and HCLE cells indicated that regulation of GLUT1 varies, likely depending on its membrane concentration. Copyright © 2014 Elsevier Inc. All rights reserved.

Parametric investigations on the saturation intensity of Coumarin 102 for stimulated emission depletion application.

PubMed

Qin, H-Y; Zhao, W-X; Zhao, W; Zhang, C; Feng, X-Q; Liu, S-P; Wang, K-G

2018-04-23

Stimulated emission depletion (STED) microscopy performed using continuous-wave (CW) lasers has been investigated and developed by Willig et al. (Nature Methods, 2007, 4(11):915) for nearly a decade. Kuang et al. (Review of Scientific Instruments, 2010, 81:053709) developed the CW STED microscopy technique with 405 nm excitation and 532 nm depletion beams. In their research, Coumarin 102 dye was adopted and was found to be depletable. In this study, a parametric investigation of the depletion of Coumarin 102 dye is carried out experimentally. The influence of the excitation and depletion beam intensities and dye concentrations on the depletion efficiency are studied in detail. The results indicate the following: (1) The highest depletion occurs for the 100 μM Coumarin 102 solution, with a 1.4 μW excitation beam and a 115.3 mW depletion beam. (2) The minimum saturation intensity (Is) of STED, that is 13 MW cm -2 , is observed when the Coumarin 102 solution concentration is 10 μM. (3) Is values calculated directly from the depletion power derived with the cross-sectional area due to the full-width-at-half-maximum (FWHM) of the depletion beam show poor accuracy, where Is may be overestimated. Thus, a correction factor for the cross-sectional area is proposed. We also find that Is is not exactly constant for a fixed excitation beam power and dye concentration. This trend indicates that the conventional suppression function η(x)=e- ln (2)ISTED(x)/Is derived from picosecond STED may cause errors in evaluating the depletion process in CW STED microscopy. © 2018 The Authors Journal of Microscopy © 2018 Royal Microscopical Society.

Novel microtubule-targeted agent 6-chloro-4-(methoxyphenyl) coumarin induces G2-M arrest and apoptosis in HeLa cells

PubMed Central

Ma, Yi-ming; Zhou, Yu-bo; Xie, Chuan-ming; Chen, Dong-mei; Li, Jia

2012-01-01

Aim: To identify a novel coumarin analogue with the highest anticancer activity and to further investigate its anticancer mechanisms. Methods: The viability of cancer cells was investigated using the MTT assay. The cell cycle progression was evaluated using both flow cytometric and Western blotting analysis. Microtubule depolymerization was observed with immunocytochemistry in vivo and a tubulin depolymerization assay in vitro. Apoptosis was demonstrated using Annexin V/Propidium Iodide (PI) double-staining and sub-G1 analysis. Results: Among 36 analogues of coumarin, 6-chloro-4-(methoxyphenyl) coumarin showed the best anticancer activity (IC50 value about 200 nmol/L) in HCT116 cells. The compound had a broad spectrum of anticancer activity against 9 cancer cell lines derived from colon cancer, breast cancer, liver cancer, cervical cancer, leukemia, epidermoid cancer with IC50 value of 75 nmol/L–1.57 μmol/L but with low cytotocitity against WI-38 human lung fibroblasts (IC50 value of 12.128 μmol/L). The compound (0.04–10 μmol/L) induced G2-M phase arrest in HeLa cells in a dose-dependent manner, which was reversible after the compound was removed. The compound (10–300 μmol/L) induced the depolymerization of purified porcine tubulin in vitro. Finally, the compound (0.04–2.5 μmol/L) induced apoptosis of HeLa cells in dose- and time-dependent manners. Conclusion: 6-Chloro-4-(methoxyphenyl) coumarin is a novel microtubule-targeting agent that induces G2–M arrest and apoptosis in HeLa cells. PMID:22266726

Kinetics and Molecular Docking Studies of 6-Formyl Umbelliferone Isolated from Angelica decursiva as an Inhibitor of Cholinesterase and BACE1.

PubMed

Ali, Md Yousof; Seong, Su Hui; Reddy, Machireddy Rajeshkumar; Seo, Sung Yong; Choi, Jae Sue; Jung, Hyun Ah

2017-09-24

Coumarins, which have low toxicity, are present in some natural foods, and are used in various herbal remedies, have attracted interest in recent years because of their potential medicinal properties. In this study, we report the isolation of two natural coumarins, namely umbelliferone ( 1 ) and 6-formyl umbelliferone ( 2 ), from Angelica decursiva , and the synthesis of 8-formyl umbelliferone ( 3 ) from 1 . We investigated the anti-Alzheimer disease (anti-AD) potential of these coumarins by assessing their ability to inhibit acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1). Among these coumarins, 2 exhibited poor inhibitory activity against AChE and BChE, and modest activity against BACE1. Structure-activity relationship analysis showed that 2 has an aldehyde group at the C-6 position, and exhibited strong anti-AD activity, whereas the presence or absence of an aldehyde group at the C-8 position reduced the anti-AD activity of 3 and 1 , respectively. In addition, 2 exhibited concentration-dependent inhibition of peroxynitrite-mediated protein tyrosine nitration. A kinetic study revealed that 2 and 3 non-competitively inhibited BACE1. To confirm enzyme inhibition, we predicted the 3D structures of AChE and BACE1, and used AutoDock 4.2 to simulate binding of coumarins to these enzymes. The blind docking studies demonstrated that these molecules could interact with both the catalytic active sites and peripheral anionic sites of AChE and BACE1. Together, our results indicate that 2 has an interesting inhibitory activity in vitro, and can be used in further studies to develop therapeutic modalities for the treatment of AD.

A coumarin-pyrazolone based fluorescent probe for selective colorimetric and fluorimetric fluoride detection: Synthesis, spectroscopic properties and DFT calculations

NASA Astrophysics Data System (ADS)

Babür, Banu; Seferoğlu, Nurgül; Seferoğlu, Zeynel

2018-06-01

A novel coumarin based fluorescence anion chemosensor (P-1) bearing pyrazolone as a receptoric part was synthesized and characterized by using FT-IR, 1H/13C NMR and HRMS for the purpose of recognition of anions in DMSO. P-1 has four tautomeric structures and the most stable tautomeric form of P-1 was determined experimentally and theoretically. The chemosensor P-1 consists two receptoric parts as free amide Nsbnd H and enamine Nsbnd H which is stabilized intramolecular H-bonding with coumarin carbonyl oxygen. P-1 interacts selectively with fluoride anion via amide Nsbnd H. The selectivity and sensitivity of probe to various anions were determined with spectrophotometric and 1H NMR titration techniques as experimentally and all results were also explained by theoretical calculations.

Synthesis and biological evaluation of novel tacrine derivatives and tacrine-coumarin hybrids as cholinesterase inhibitors.

PubMed

Hamulakova, Slavka; Janovec, Ladislav; Hrabinova, Martina; Spilovska, Katarina; Korabecny, Jan; Kristian, Pavol; Kuca, Kamil; Imrich, Jan

2014-08-28

A series of novel tacrine derivatives and tacrine-coumarin heterodimers were designed, synthesized, and biologically evaluated for their potential inhibitory effect on both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Of these compounds, tacrine-coumarin heterodimer 7c and tacrine derivative 6b were found to be the most potent inhibitors of human AChE (hAChE), demonstrating IC50 values of 0.0154 and 0.0263 μM. Ligands 6b, 6c, and 7c exhibited the highest levels of inhibitory activity against human BuChE (hBuChE), demonstrating IC50 values that range from 0.228 to 0.328 μM. Docking studies were performed in order to predict the binding modes of compounds 6b and 7c with hAChE/hBuChE.

Determination of coumarin, vanillin, and ethyl vanillin in vanilla extract products: liquid chromatography mass spectrometry method development and validation studies.

PubMed

de Jager, Lowri S; Perfetti, Gracia A; Diachenko, Gregory W

2007-03-23

A LC-MS method was developed for the determination of coumarin, vanillin, and ethyl vanillin in vanilla products. Samples were analyzed using LC-electrospray ionization (ESI)-MS in the positive ionization mode. Limits of detection for the method ranged from 0.051 to 0.073 microg mL(-1). Using the optimized method, 24 vanilla products were analyzed. All samples tested negative for coumarin. Concentrations ranged from 0.38 to 8.59 mg mL(-1) (x =3.73) for vanillin and 0.33 to 2.27 mg mL(-1) (x =1.03) for ethyl vanillin. The measured concentrations are compared to values calculated using UV monitoring and to results reported in a similar survey in 1988. Analytical results, method precision, and accuracy data are presented.

Palladium-catalyzed substitution of (coumarinyl)methyl acetates with C-, N-, and S-nucleophiles

PubMed Central

Chattopadhyay, Kalicharan; Fenster, Erik; Grenning, Alexander J

2012-01-01

Summary The palladium-catalyzed nucleophilic substitution of (coumarinyl)methyl acetates is described. The reaction proceeds though a palladium π-benzyl-like complex and allows for many different types of C-, N-, and S-nucleophiles to be regioselectively added to the biologically active coumarin motif. This new method was utilized to prepare a 128-membered library of aminated coumarins for biological screening. PMID:23019448

Bibliography of Soviet Laser Developments. Number 71, May - June 1984.

DTIC Science & Technology

1985-08-01

d * Coumarin *o..*....... .. o... -- e. Phthalimide ...... o..... o. .. ... --- f . Cyanine .. ... .o o . .. .. .. see. --- go Xanthene...Barinova, E.Yu. (MGU). Determining the concentration of nitrogen in gallium phosphide from its photoluminescence spectrum. VMUFA, no. 3, 1984, 59-62. 23...characteristics for lasing in solutions of rhodamine 6G in a small-base resonator. OPSPA, v.56, no.5, 1984, 884-888. 5 a’ F, c. Polymethine d. Coumarin e

Bibliography of Soviet Laser Developments, Number 83, May - June 1986.

DTIC Science & Technology

1987-09-01

Polymethine ..................... 8 d. Coumarin .. .o-... . .. . e. Phthalimide ................. --- f. Cyanine ....................... . - - g. Xanthene...KVEKA, no. 6, 1986, 1155-1160. 25. Kostanyan, R.B.; Sanamyan, T.V. 0. Stucy on lifetimes of erbium levels in lutecium aluminum garnet. DANAA, no. 3, 1985...60, no. 5, 1986, 937-942. d. Coumarin e. Phthalimide f. Cyanine g. Xanthene h. POPOP 2. Inorganic Liquids C. GAS LASERS 1. Theory 60. Basov, N.G

Coumarin Derivative Directly Coordinated to Lanthanides Acts as an Excellent Antenna for UV-Vis and Near-IR Emission.

PubMed

Guzmán-Méndez, Óscar; González, Federico; Bernès, Sylvain; Flores-Álamo, Marcos; Ordóñez-Hernández, Javier; García-Ortega, Héctor; Guerrero, Joselin; Qian, Wenjie; Aliaga-Alcalde, Nuria; Gasque, Laura

2018-02-05

A chelating coumarin-derived ligand sensitizes all emitting lanthanide ions in the solid state and gives high absolute quantum yields for ethanol solutions of complexes of Sm, Eu, Tb, and Dy, above 20% for the last two. Crystal structures of these four complexes are [Ln(Cum) 3 (H 2 O)(X)]·X where X = MeOH or EtOH.

Anti-Inflammatory Effect of Angelica gigas via Heme Oxygenase (HO)-1 Expression.

PubMed

Cho, Joon Hyeong; Kwon, Jung Eun; Cho, Youngmi; Kim, Inhye; Kang, Se Chan

2015-06-15

Angelica gigas (AG) is effective against various medical conditions such as bacterial infection, inflammation, and cancer. It contains a number of coumarin compounds and the group of interest is the pyranocoumarin, which comprises decursin and decursinol angelate. This group has an effect on controlling inflammation, which is caused by excessive nitric oxide (NO) production. Heme oxygenases (HOs), particularly HO-1, play a role in regulating the production of NO. Thus, this study aimed to investigate the anti-inflammatory effects of AG by measuring HO-1 expression. Treatments with CH2Cl2 layer and Angelica gigas extract (AGE) showed the highest NO inhibition effects. Decursin, decursinol angelate, and nodakenin were isolated from the CH2Cl2 layer of AGE. Decursin also demonstrated the highest anti-oxidative effect among the coumarins. Although decursin had the best NO inhibition and anti-oxidative effects, the effects of AGE treatment far surpassed that of decursin. This is owing to the combination effect of the coumarins present within AGE, which is a solvent extract of AG. The expression of HO-1 is an effective indicator of the anti-inflammatory effects of AG. Based on the results of the coumarin compounds, HO-1 expression was found to be dose dependent and specific to decursin.

Anti-Inflammatory Effect of Angelica gigas via Heme Oxygenase (HO)-1 Expression

PubMed Central

Cho, Joon Hyeong; Kwon, Jung Eun; Cho, Youngmi; Kim, Inhye; Kang, Se Chan

2015-01-01

Angelica gigas (AG) is effective against various medical conditions such as bacterial infection, inflammation, and cancer. It contains a number of coumarin compounds and the group of interest is the pyranocoumarin, which comprises decursin and decursinol angelate. This group has an effect on controlling inflammation, which is caused by excessive nitric oxide (NO) production. Heme oxygenases (HOs), particularly HO-1, play a role in regulating the production of NO. Thus, this study aimed to investigate the anti-inflammatory effects of AG by measuring HO-1 expression. Treatments with CH2Cl2 layer and Angelica gigas extract (AGE) showed the highest NO inhibition effects. Decursin, decursinol angelate, and nodakenin were isolated from the CH2Cl2 layer of AGE. Decursin also demonstrated the highest anti-oxidative effect among the coumarins. Although decursin had the best NO inhibition and anti-oxidative effects, the effects of AGE treatment far surpassed that of decursin. This is owing to the combination effect of the coumarins present within AGE, which is a solvent extract of AG. The expression of HO-1 is an effective indicator of the anti-inflammatory effects of AG. Based on the results of the coumarin compounds, HO-1 expression was found to be dose dependent and specific to decursin. PMID:26083119

Design and application of a fluorogenic assay for monitoring inflammatory caspase activity.

PubMed

Ranganathan, Raj; Lenti, Gena; Tassone, Nicholas M; Scannell, Brian J; Southern, Cathrine A; Karver, Caitlin E

2018-02-15

Various fluorogenic assays exist for monitoring the activity of inflammatory caspases. However, there are no continuous assays that provide C-terminal substrate sequence specificity for inflammatory caspases. As a first step towards this, we have developed a continuous in vitro assay that relies on monitoring emission from tryptophan after cleavage of a quenching coumarin chromophore. The coumarin can be attached as an amino acid side chain or capping the C-terminus of the peptide. When the coumarin is a side chain, it allows for C-terminal and N-terminal sequence specificities to be explored. Using this assay, we obtained Michaelis-Menten kinetic data for four proof-of-principle peptides: WEHD-AMC (K M  = 15 ± 2 μM), WEHD-MCA (K M  = 93 ± 19 μM), WEHDG-MCA (K M  = 21 ± 6 μM) and WEHDA-MCA (K M  = 151 ± 37 μM), where AMC is 7-amino-4-methylcoumarin and MCA is β-(7-methoxy-coumarin-4-yl)-Ala. The results indicate the viability of this new assay approach in the design of effective fluorogenic substrates for inflammatory caspases. Copyright © 2017 Elsevier Inc. All rights reserved.

Antimicrobial Effects of 7,8-Dihydroxy-6-Methoxycoumarin and 7-Hydroxy-6-Methoxycoumarin Analogues against Foodborne Pathogens and the Antimicrobial Mechanisms Associated with Membrane Permeability.

PubMed

Yang, Ji-Yeon; Park, Jun-Hwan; Lee, Myung-Ji; Lee, Ji-Hoon; Lee, Hoi-Seon

2017-10-03

The antimicrobial effects of 7,8-dihydroxy-6-methoxycoumarin and 7-hydroxy-6-methoxycoumarin isolated from Fraxinus rhynchophylla bark and of their structural analogues were determined in an attempt to develop natural antimicrobial agents against the foodborne pathogens Escherichia coli, Bacillus cereus, Staphylococcus intermedius, and Listeria monocytogenes. To elucidate the relationship between structure and antimicrobial activity for the coumarin analogues, isolated constituents and their structural analogues were evaluated against foodborne pathogens. Based on the culture plate inhibition zones and MICs, 6,7-dimethoxycoumarin, 7,8-dihydroxy-6-methoxycoumarin, 7-hydroxy-6-methoxycoumarin, and 7-methoxycoumarin, containing a methoxy functional group on the coumarin skeleton, had the notable antimicrobial activity against foodborne pathogens. However, 7-hydroxycoumarin and 6,7-dihydroxycoumarin, which contained a hydroxyl functional group on the coumarin skeleton, had no antimicrobial activity against these pathogens. An increase in cell membrane permeability was confirmed by electron microscopy observations, and release of extracellular ATP and cell constituents followed treatment with the ethyl acetate fraction of F. rhynchophylla extract. These findings indicate that F. rhynchophylla extract and coumarin analogues have potential for use as antimicrobial agents against foodborne pathogens and that the antimicrobial mechanisms are associated with the loss of cell membrane integrity.

Hyaluronic Acid as a Target for Intervention in Prostate Cancer Metastases

DTIC Science & Technology

2011-06-01

Coumarin (HMC) is an inhibitor of hyaluronan synthase. It is commonly available in herbal supplements and, up to now, has been utilized mainly for...commonly available in herbal supplements and, up to now, has been utilized mainly for digestion complaints. We propose that it may be efficacious in the...metastatic prostate cancer cells. 7-Hydroxy-4-Methyl Coumarin (HMC) is an inhibitor of hyaluronan synthase. It is commonly available in herbal supplements

Arthropod repellency, especially tick (Ixodes ricinus), exerted by extract from Artemisia abrotanum and essential oil from flowers of Dianthus caryophyllum.

PubMed

Tunón, H; Thorsell, W; Mikiver, A; Malander, I

2006-06-01

A toluene extract of southernwood (Artemisia abrotanum) and the essential oil from flowers of carnation (Dianthus caryophyllum ) exerted pronounced a repellent effect both against ticks (nymphs of Ixodes ricinus) and yellow fever mosquitoes (Aedes aegypti). The most potent repellents found were coumarin and thujyl alcohol from A. abrotanum and phenylethanol from D. caryophyllum where coumarin and thujyl alcohol were also detected.

Thorough investigation of the oxygen heterocyclic fraction of lime (Citrus aurantifolia (Christm.) Swingle) juice.

PubMed

Costa, Rosaria; Russo, Marina; De Grazia, Selenia; Grasso, Elisa; Dugo, Paola; Mondello, Luigi

2014-04-01

Reversed-phase-HPLC analysis by means of superficially porous silica particle columns (fused-core) was applied to the investigation of flavonoids, coumarins, and psoralens in lime juice samples. Hesperidin (367.0 ± 16.0 ppm) and eriocitrin (148.0 ± 7.9 ppm) were the most abundant flavonoids. Fifteen coumarins and furocoumarins were determined, including bergamottin (29.6 ± 1.1 ppm), 5-geranyloxy-7-methoxycoumarin (16.5 ± 0.6 ppm), and oxypeucedanin hydrate (9.9 ± 0.5 ppm) as predominant compounds. These molecules are today well known for their beneficial effects on human health. As a consequence, the present study, beyond investigating for the first time the chemical composition of lime juice, highlights also its health-promoting qualities, due to its content of flavonoids and coumarins. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Bichromophoric dyes for wavelength shifting of dye-protein fluoromodules.

PubMed

Pham, Ha H; Szent-Gyorgyi, Christopher; Brotherton, Wendy L; Schmidt, Brigitte F; Zanotti, Kimberly J; Waggoner, Alan S; Armitage, Bruce A

2015-03-28

Dye-protein fluoromodules consist of fluorogenic dyes and single chain antibody fragments that form brightly fluorescent noncovalent complexes. This report describes two new bichromophoric dyes that extend the range of wavelengths of excitation or emission of existing fluoromodules. In one case, a fluorogenic thiazole orange (TO) was attached to an energy acceptor dye, Cy5. Upon binding to a protein that recognizes TO, red emission due to efficient energy transfer from TO to Cy5 replaces the green emission observed for monochromophoric TO bound to the same protein. Separately, TO was attached to a coumarin that serves as an energy donor. The same green emission is observed for coumarin-TO and TO bound to a protein, but efficient energy transfer allows violet excitation of coumarin-TO, versus longer wavelength, blue excitation of monochromophoric TO. Both bichromophores exhibit low nanomolar KD values for their respective proteins, >95% energy transfer efficiency and high fluorescence quantum yields.

Bichromophoric Dyes for Wavelength Shifting of Dye-Protein Fluoromodules

PubMed Central

Pham, Ha H.; Szent-Gyorgyi, Christopher; Brotherton, Wendy L.; Schmidt, Brigitte F.; Zanotti, Kimberly J.; Waggoner, Alan S.

2015-01-01

Dye-protein fluoromodules consist of fluorogenic dyes and single chain antibody fragments that form brightly fluorescent noncovalent complexes. This report describes two new bichromophoric dyes that extend the range of wavelengths of excitation or emission of existing fluoromodules. In one case, a fluorogenic thiazole orange (TO) was attached to an energy acceptor dye, Cy5. Upon binding to a protein that recognizes TO, red emission due to efficient energy transfer from TO to Cy5 replaces the green emission observed for monochromophoric TO bound to the same protein. Separately, TO was attached to a coumarin that serves as an energy donor. The same green emission is observed for coumarin-TO and TO bound to a protein, but efficient energy transfer allows violet excitation of coumarin-TO, versus longer wavelength, blue excitation of monochromophoric TO. Both bichromophores exhibit low nanomolar KD values for their respective proteins, >95% energy transfer efficiency and high fluorescence quantum yields. PMID:25679477

Covalent chemical functionalization enhances the biodegradation of graphene oxide

NASA Astrophysics Data System (ADS)

Kurapati, Rajendra; Bonachera, Fanny; Russier, Julie; Rajukrishnan Sureshbabu, Adukamparai; Ménard-Moyon, Cécilia; Kostarelos, Kostas; Bianco, Alberto

2018-01-01

Biodegradation of the graphene-based materials is an emerging issue due to their estimated widespread usage in different industries. Indeed, a few concerns have been raised about their biopersistence. Here, we propose the design of surface-functionalized graphene oxide (GO) with the capacity to degrade more effectively compared to unmodified GO using horseradish peroxidase (HRP). For this purpose, we have functionalized the surface of GO with two well-known substrates of HRP namely coumarin and catechol. The biodegradation of all conjugates has been followed by Raman, dynamic light scattering and electron microscopy. Molecular docking and gel electrophoresis have been carried out to gain more insights into the interaction between GO conjugates and HRP. Our studies have revealed better binding when GO is functionalized with coumarin or catechol compared to control GOs. All results prove that GO functionalized with coumarin and catechol moieties display a faster and more efficient biodegradation over GO.

A colorimetric and fluorogenic probe for bisulfite using benzopyrylium as the recognition unit.

PubMed

Zhang, Yun; Zhang, Xiangwen; Yang, Xiao-Feng; Zhang, Juan

2017-11-01

A coumarin-benzopyrylium (CB) platform has been developed for the colorimetric and fluorogenic detection of bisulfite. The proposed probe utilizes coumarin as the fluorophore and positively charged benzopyrylium as the reaction site. The method employs the nucleophilic addition of bisulfite to the benzopyrylium moiety of CB to inactivate the electron-deficient oxonium ion. The driving force for photo-induced electron transfer is considerably diminished, thereby promoting the emission intensity of the coumarin fluorophore. The fluorescence intensity at 510 nm is linear with bisulfite concentration over a range of 0.2-7.5 μM with a detection limit of 42 nM (3δ). CB shows a rapid response (within 30 s) and high selectivity and sensitivity for bisulfite. Preliminary studies show that CB has great potential for bisulfite detection in real samples and in living cells. Copyright © 2017 John Wiley & Sons, Ltd.

Exploring Cancer Therapeutics with Natural Products from African Medicinal Plants, Part I: Xanthones, Quinones, Steroids, Coumarins, Phenolics and other Classes of Compounds.

PubMed

Simoben, Conrad V; Ibezim, Akachukwu; Ntie-Kang, Fidele; Nwodo, Justina N; Lifongo, Lydia L

2015-01-01

Cancer is known to be the second most common disease-related cause of death among humans. In drug discovery programs anti-cancer chemotherapy remains quite challenging due to issues related to resistance. Plants used in traditional medicine are known to contribute significantly within a large proportion of the African population. A survey of the literature has led to the identification of ~400 compounds from African medicinal plants, which have shown anti-cancer, anti-proliferation, anti-tumor and/or cytotoxic activities, tested by in vitro and in vivo assays (from mildly active to very active), mainly alkaloids, terpenoids, flavonoids, coumarins, phenolics, polyacetylates, xanthones, quinones, steroids and lignans. The first part of this review series focuses on xanthones, quinones, steroids, coumarins, phenolics and other compound classes, while part II is focused on alkaloids, terpenoids, flavonoids.

Structural insights into substrate specificity of Feruloyl-CoA 6’-Hydroxylase from Arabidopsis thaliana

DOE PAGES

Sun, Xinxiao; Zhou, Dayong; Kandavelu, Palani; ...

2015-05-20

Coumarins belong to an important class of plant secondary metabolites. Feruloyl-CoA 6’-hydroxylase (F6’H), a 2-oxoglutarate dependent dioxygenase (2OGD), catalyzes a pivotal step in the biosynthesis of a simple coumarin scopoletin. In this study, we determined the 3-dimensional structure of the F6’H1 apo enzyme by X-ray crystallography. It is the first reported structure of a 2OGD enzyme involved in coumarin biosynthesis and closely resembles the structure of Arabidopsis thaliana anthocyanidin synthase. To better understand the mechanism of enzyme catalysis and substrate specificity, we also generated a homology model of a related ortho-hydroxylase (C 2’H) from sweet potato. By comparing these twomore » structures, we targeted two amino acid residues and verified their roles in substrate binding and specificity by site-directed mutagenesis.« less

Structural insights into substrate specificity of Feruloyl-CoA 6’-Hydroxylase from Arabidopsis thaliana

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

Sun, Xinxiao; Zhou, Dayong; Kandavelu, Palani

Coumarins belong to an important class of plant secondary metabolites. Feruloyl-CoA 6’-hydroxylase (F6’H), a 2-oxoglutarate dependent dioxygenase (2OGD), catalyzes a pivotal step in the biosynthesis of a simple coumarin scopoletin. In this study, we determined the 3-dimensional structure of the F6’H1 apo enzyme by X-ray crystallography. It is the first reported structure of a 2OGD enzyme involved in coumarin biosynthesis and closely resembles the structure of Arabidopsis thaliana anthocyanidin synthase. To better understand the mechanism of enzyme catalysis and substrate specificity, we also generated a homology model of a related ortho-hydroxylase (C 2’H) from sweet potato. By comparing these twomore » structures, we targeted two amino acid residues and verified their roles in substrate binding and specificity by site-directed mutagenesis.« less

Photocatalytic performance of titania nanospheres deposited on graphene in coumarin oxidation reaction

NASA Astrophysics Data System (ADS)

Wojtoniszak, M.; Zielinska, B.; Kalenczuk, R. J.; Mijowska, E.

2012-03-01

In this paper, we present a study on enhanced photocatalytic performance of TiO2 nanospheres deposited on graphene (n-TiO2-G) in a process of coumarin oxidation. The enhancement of the photoactivity has been observed in respect to commercial TiO2 P25. The presented material was prepared in two steps: (i) hydrolysis of titanium (IV) butoxide (TBT) in ethanol solution with simultaneous deposition on graphene oxide (GO) and (ii) calcination of TiO2-GO to form anatase-TiO2 and reduce GO to graphene. The nanomaterial was characterized by transmission electron microscopy (TEM), energy dispersive X-ray spectroscopy (EDX), thermogravimetric analysis (TGA), Fourier-Transformed Infrared spectroscopy and Raman spectroscopy. In the presented photocatalytic process the fluorescence was used to detect •OH formed on a photo-illuminated n-TiO2-G surface using coumarin which readily reacted with •OH to produce highly fluorescent 7-hydroxycoumarin.

A UBI 31-38 Peptide-coumarin Conjugate: Photophysical Features, Imaging Tracking and Synergism with Amphotericin B Against Cryptococcus.

PubMed

Ferreira, Soraya M Z M D; Carneiro, Hellem C; Alves, Rosemeire B; Batista, Ana Carolina S; da Silva Junior, Eufranio N; Dias, Gleiston G; Resende, Jarbas M; Santos, Daniel A; Oliveira, Debora L; Rodrigues, Marcio L; Freitas, Rossimiriam P

2018-01-01

Cryptococcosis is a fungal disease of global significance for which new effective treatments are needed. The conjugation of the synthetic antimicrobial peptide fragment UBI 31-38 to a coumarin derivative showed to be an effective approach for the design of a novel anticryptococcal agent. In addition to antifungal activity, the conjugate exhibited intense fluorescence, which could be valuable for mechanistic investigations of this molecule. In this work, we studied the photophysical properties of the conjugate and confocal scanning laser microscopy was used to inspect the distribution of the peptide-coumarin conjugate in Cryptococcus cell. The synergism of this compound with amphotericin B or fluconazole against C. gattii and C. neoformans strains was also investigated. The results indicated that the fluorescent conjugate alone as well as its combination with amphotericin B are promising tools against cryptococcosis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Microbial models of mammalian metabolism: production of novel alpha-diketone metabolites of warfarin and phenprocoumon using Aspergillus niger.

PubMed

Rizzo, J D; Davis, P J

1988-12-01

1. The coumarin anticoagulants warfarin and phenprocoumon were metabolized by Aspergillus niger via oxidative ring cleavage to yield the corresponding alpha-diketone metabolites. 2. Structural identification was based upon physical, spectral, and chromatographic comparisons of isolated metabolites and synthetic standards generated by the oxidative cleavage of warfarin or phenprocoumon with pyridinium chlorochromate. 3. This pathway of metabolism has been previously observed for coumarin anticoagulants in mammalian systems.

Combining silver catalysis and organocatalysis: a sequential Michael addition/hydroalkoxylation one-pot approach to annulated coumarins.

PubMed

Hack, Daniel; Chauhan, Pankaj; Deckers, Kristina; Hermann, Gary N; Mertens, Lucas; Raabe, Gerhard; Enders, Dieter

2014-10-03

A highly stereoselective one-pot procedure for the synthesis of five-membered annulated hydroxycoumarins has been developed. By merging primary amine catalysis with silver catalysis, a series of functionalized coumarin derivatives were obtained in good yields (up to 91%) and good to excellent enantioselectivities (up to 99% ee) via a Michael addition/hydroalkoxylation reaction. Depending on the substituents on the enynone, the synthesis of annulated six-membered rings is also feasible.

Genetically encoded fluorescent coumarin amino acids

DOEpatents

Wang, Jiangyun; Xie, Jianming; Schultz, Peter G.

2010-10-05

The invention relates to orthogonal pairs of tRNAs and aminoacyl-tRNA synthetases that can incorporate the coumarin unnatural amino acid L-(7-hydroxycoumarin-4-yl) ethylglycine into proteins produced in eubacterial host cells such as E. coli. The invention provides, for example but not limited to, novel orthogonal synthetases, methods for identifying and making the novel synthetases, methods for producing proteins containing the unnatural amino acid L-(7-hydroxycoumarin-4-yl)ethylglycine and related translation systems.

Genetically encoded fluorescent coumarin amino acids

DOEpatents

Wang, Jiangyun [San Diego, CA; Xie, Jianming [San Diego, CA; Schultz, Peter G [La Jolla, CA

2012-06-05

The invention relates to orthogonal pairs of tRNAs and aminoacyl-tRNA synthetases that can incorporate the coumarin unnatural amino acid L-(7-hydroxycoumarin-4-yl)ethylglycine into proteins produced in eubacterial host cells such as E. coli. The invention provides, for example but not limited to, novel orthogonal synthetases, methods for identifying and making the novel synthetases, methods for producing proteins containing the unnatural amino acid L-(7-hydroxycoumarin-4-yl)ethylglycine and related translation systems.

Synthesis and biological evaluation of coumarin derivatives containing imidazole skeleton as potential antibacterial agents.

PubMed

Hu, Yang; Shen, Yufeng; Wu, Xiaohu; Tu, Xiao; Wang, Gao-Xue

2018-01-01

Emergence of multidrug-resistant bacteria causes an urgent need for new generation of antibiotics, which may have a different mechanism of inhibition or killing action from the existing. Here, we report on the design, synthesis, and biological evaluation of thirty-nine coumarin derivatives in order to solve the antibacterial resistance by targeting at the inhibition of biosynthesis pathway of fatty acids. Their antibacterial activities against Escherichia coli, Staphylococcus aureus, Streptococcus agalactiae, and Flavobacterium cloumnare are tested and action mechanism against the key enzyme in bacterial fatty acid synthesis pathway are studied. The results show that compounds 13 and 18 have potent and broad spectrum antimicrobial activity. In addition, 9, 14 and 19 show eminent antimicrobial efficacy toward S. aureus, S. agalactiae, and F. cloumnare. Mechanistically, coumarin derivatives display the antibacterial activity via the control of FabI and FabK function. The structure-activity relationship analysis indicate that the length of linker and imidazole substitute group could significantly influence the antimicrobial activity, as well as the inhibitory activity against FabI and FabK. The structural optimization analysis of coumarin suggest that derivatives 9, 13, 14, 18 and 19 could be a viable way of preventing and controlling bacteria and considered as promising lead compounds for the development of commercial drugs. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Structures of human monoamine oxidase B complexes with selective noncovalent inhibitors: safinamide and coumarin analogs.

PubMed

Binda, Claudia; Wang, Jin; Pisani, Leonardo; Caccia, Carla; Carotti, Angelo; Salvati, Patricia; Edmondson, Dale E; Mattevi, Andrea

2007-11-15

Structures of human monoamine oxidase B (MAO B) in complex with safinamide and two coumarin derivatives, all sharing a common benzyloxy substituent, were determined by X-ray crystallography. These compounds competitively inhibit MAO B with Ki values in the 0.1-0.5 microM range that are 30-700-fold lower than those observed with MAO A. The inhibitors bind noncovalently to MAO B, occupying both the entrance and the substrate cavities and showing a similarly oriented benzyloxy substituent.

Coumarin versus Chromone Monoamine Oxidase B Inhibitors: Quo Vadis?

PubMed

Fonseca, André; Reis, Joana; Silva, Tiago; Matos, Maria João; Bagetta, Donatella; Ortuso, Francesco; Alcaro, Stefano; Uriarte, Eugenio; Borges, Fernanda

2017-08-24

Because of the lack of significant disease-modifying drugs for neurodegenerative disorders, a pressing need for new chemical entities endowed with IMAO-B still exists. Within this framework, and for the first time, a study was performed to compare coumarin- and chomone-3-phenylcarboxamide scaffolds. Compounds 10a and 10b were the most potent, selective, and reversible noncompetitive IMAO-B. The benzopyrone sp 2 oxygen atom was found to be position independent and a productive contributor for the ligand-enzyme complex stability.

Synthesis of Two Coumarin-Derived Schiff Bases and Investigation of theirs Selectivity for Zn2.

PubMed

Fan, Long

2017-07-01

In this study, the coumarin-derived schiff bases (HL 1 and HL 2 ) have been designed and synthesized. Upon the addition of Zn 2+ , both of them show significant fluorescence enhancement owing to inhibits PET and ESIPT process respectively. However, the receptor HL 2 response toward Cd 2+ , Mg 2+ , Ba 2+ , Ca 2+ besides Zn 2+ and exhibits fluorescence enhancement but not enough to detection of the concentration levels of Zn 2+ .

Effects of Solvation on One- and Two-Photon Spectra of Coumarin Derivatives: A Time-Dependent Density Functional Theory Study (Postprint)

DTIC Science & Technology

2007-01-01

2003. 15 A. Barik , S. Nath, and H. Pal, J . Chem. Phys. 119, 10202 2003. 16 A. Fisher, C. Cremer, and E. H. K. Stelzer, Appl. Opt. 34, 1989 1995...Hardened Materials Branch //Signature// TIM J . SCHUMACHER, Chief Survivability and Sensor Materials Division This...coumarin 152, 152A, 522, 153, 307, and 151. 094303-2 Nguyen, Day, and Pachter J . Chem. Phys. 126, 094303 2007 Downloaded 06 Nov 2007 to 134.131.125.49

Coumarin/BODIPY Hybridisation for Ratiometric Sensing of Intracellular Polarity Oscillation.

PubMed

Bai, Yang; Shi, Xiangchao; Chen, Yuncong; Zhu, Chengcheng; Jiao, Yang; Han, Zhong; He, Weijiang; Guo, Zijian

2018-05-23

With different polarity responses, coumarin and 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) were hybridised to construct polarity fluorescent sensors, CBDP and iso-CBDP, to overcome the disadvantages of solvatochromic sensors in ratiometric polarity sensing. Only CBDP displayed an emission ratio (I Cou /I BDP , coumarin to BODIPY emissions) that increased with an exponential dependence on medium relative permittivity over a wide polarity range (ϵ r <57.9). This sensing ability of CBDP was not affected by medium pH; viscosity; and most intracellular species, especially reactive oxygen, nitrogen, and sulfur species. Apart from local cytoplasmic polarity quantification through lambda imaging, CBDP enables real-time ratiometric imaging for intracellular polarity oscillation induced by oxidative stimulation. Ratiometric polarity flow cytometry was developed, for the first time, with CBDP, which demonstrated that a high concentration H 2 O 2 induced cytoplasmic polarity enhancement, whereas pre-incubation with N-acetyl-l-cysteine inhibited this effect. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Coumarins from the Herb Cnidium monnieri and Chemically Modified Derivatives as Antifoulants against Balanus albicostatus and Bugula neritina Larvae

PubMed Central

Wang, Zhan-Chang; Feng, Dan-Qing; Ke, Cai-Huan

2013-01-01

In the search for new environmental friendly antifouling (AF) agents, four coumarins were isolated from the herbal plant Cnidium monnieri, known as osthole (1), imperatorin (2), isopimpinellin (3) and auraptenol (4). Furthermore, five coumarin derivatives, namely 8-epoxypentylcoumarin (5), meranzin hydrate (6), 2′-deoxymetranzin hydrate (7), 8-methylbutenalcoumarin (8), and micromarin-F (9) were synthesized from osthole. Compounds 1, 2, 4, 7 showed high inhibitory activities against larval settlement of Balanus albicostatus with EC50 values of 4.64, 3.39, 3.38, 4.67 μg mL−1. Compound 8 could significantly inhibit larval settlement of Bugula neritina with an EC50 value of 3.87 μg mL−1. The impact of functional groups on anti-larval settlement activities suggested that the groups on C-5′ and C-2′/C-3′ of isoamylene chian could affect the AF activities. PMID:23303279

A novel coumarin-quinone derivative SV37 inhibits CDC25 phosphatases, impairs proliferation, and induces cell death.

PubMed

Bana, Emilie; Sibille, Estelle; Valente, Sergio; Cerella, Claudia; Chaimbault, Patrick; Kirsch, Gilbert; Dicato, Mario; Diederich, Marc; Bagrel, Denyse

2015-03-01

Cell division cycle (CDC) 25 proteins are key phosphatases regulating cell cycle transition and proliferation by regulating CDK/cyclin complexes. Overexpression of these enzymes is frequently observed in cancer and is related to aggressiveness, high-grade tumors and poor prognosis. Thus, targeting CDC25 by compounds, able to inhibit their activity, appears a good therapeutic approach. Here, we describe the synthesis of a new inhibitor (SV37) whose structure is based on both coumarin and quinone moieties. An analytical in vitro approach shows that this compound efficiently inhibits all three purified human CDC25 isoforms (IC50 1-9 µM) in a mixed-type mode. Moreover, SV37 inhibits growth of breast cancer cell lines. In MDA-MB-231 cells, reactive oxygen species generation is followed by pCDK accumulation, a mark of CDC25 dysfunction. Eventually, SV37 treatment leads to activation of apoptosis and DNA cleavage, underlining the potential of this new type of coumarin-quinone structure. © 2013 Wiley Periodicals, Inc.

Solvent effects on the photophysical properties of coumarin dye

NASA Astrophysics Data System (ADS)

Bhavya, P.; Melavanki, Raveendra; Manjunatha, M. N.; Koppal, Varsha; Patil, N. R.; Muttannavar, V. T.

2018-05-01

The absorption and emission spectrum of fluorescent coumarin dye namely, 3-Hydroxy-3-[2-oxo-2-(3-oxo-3H-benzo[f]chromen-2-yl)-ethyl]-1,3-dihydro-indol-2-one [3HBCD] has been recorded at room temperature in solvents of different polarities. The exited state dipole moments (μe) were estimated from Lippert's, Bakhshiev's and Kawski-Chamma-Viallet's equations using the variation of Stoke's shift with the solvent dielectric constant and refractive index. The geometry of the molecule was fully optimized and the μg was also calculated theoretically by Gaussian 03 software using B3LYP/6-31g* level of theory. The μg and μg were calculated by means of solvatochromic shift method. It was observed that μe was higher than μg, indicating a substantial redistribution of the π-electron densities in a more polar excited state for the selected coumarin dye. Further, the changes in the dipole moment (Δμ) was calculated from solvatochromic shift method.

Dimers of coumarin-1,2,3-triazole hybrids bearing alkyl spacer: Design, microwave-assisted synthesis, molecular docking and evaluation as antimycobacterial and antimicrobial agents

NASA Astrophysics Data System (ADS)

Ashok, Dongamanti; Gundu, Srinivas; Aamate, Vikas Kumar; Devulapally, Mohan Gandhi; Bathini, Raju; Manga, Vijjulatha

2018-04-01

The present study demonstrated the synthesis of new series of coumarin-1,2,3-triazole hybrids under microwave irradiation method. Several dimers of coumarin based 1,2,3-triazole derivatives were synthesized and their antimycobacterial and antimicrobial activities were investigated. The antimycobacterial activity screening results revealed that compounds 6i and 6j were the most active against Mycobacterium tuberculosis H37Rv strain. The active compounds were further evaluated for cytotoxicity with HEK cell lines and exhibited less % of inhibition. The same synthetic hybrids were evaluated for their antimicrobial activity against various bacterial strains and fungal strains and compounds 6e, 6h, 6i and 6j were found to be the most promising antimicrobial potent molecules. Furthermore, the active compounds against Mycobacterium tuberculosis were evaluated for their molecular docking studies against pantothenate synthetase (PS) enzyme of MTB and the docking results are in well agreement with the antitubercular evaluation results.

Antiproliferative Constituents of Geopropolis from the Bee Melipona scutellaris.

PubMed

da Cunha, Marcos Guilherme; Rosalen, Pedro Luiz; Franchin, Marcelo; de Alencar, Severino Matias; Ikegaki, Masaharu; Ransom, Tanya; Beutler, John Albert

2016-02-01

Fractionation of geopropolis from Melipona scutellaris, guided by antiproliferative activity against two colon cancer cell lines (COLO205 and KM12), led to the isolation of two new cinnamic acid esters, mammea-type coumarins 5,7-dihydroxy-6-(3-methyl-2-butenyl)-8-(4-cinnamoyl-3-methyl-1-oxobutyl)-4-propyl-coumarin (1) and 5,7-dihydroxy-6-(4-cinnamoyl-3-methyl-1-oxobutyl)-4-phenylcoumarin (2), along with five known coumarins, mammeigin (3), hydroxymammeigin (4), mammeisin (5), cinnamoyloxy-mammeisin (6), and mammein (7), and the prenylated benzophenone ent-nemorosone (8). Among the isolated compounds, 5 and 7 showed the highest cell growth inhibition against COLO205 (GI50 9.7 and 10.7 µM, respectively) and KM12 (GI50 12.0 and 10.9 µM, respectively). The presence of these compounds suggests that plants of Clusiaceae family, especially the genera Kielmeyera and Clusia, are likely to be major sources of geopropolis produced by M. scutellaris. Georg Thieme Verlag KG Stuttgart · New York.

Antiproliferative Constituents of Geopropolis from the Bee Melipona scutellaris

PubMed Central

da Cunha, Marcos Guilherme; Rosalen, Pedro Luiz; Franchin, Marcelo; de Alencar, Severino Matias; Ikegaki, Masaharu; Ransom, Tanya; Beutler, John Albert

2016-01-01

Fractionation of geopropolis from Melipona scutellaris, guided by antiproliferative activity against two colon cancer cell lines (COLO205 and KM12), led to the isolation of two new cinnamic acid esters, mammea-type coumarins 5,7-dihydroxy-6-(3-methyl-2-butenyl)-8-(4-cinnamoyl-3-methyl-1-oxobutyl)-4-propyl-coumarin (1) and 5,7-dihydroxy-6-(4-cinnamoyl-3-methyl-1-oxobutyl)-4-phenylcoumarin (2), along with five known coumarins, mammeigin (3), hydroxymammeigin (4), mammeisin (5), cinnamoyloxy-mammeisin (6), and mammein (7), and the prenylated benzophenone ent-nemorosone (8). Among the isolated compounds, 5 and 7 showed the highest cell growth inhibition against COLO205 (GI50 9.7 and 10.7 μM, respectively) and KM12 (GI50 12.0 and 10.9 μM, respectively). The presence of these compounds suggests that plants of Clusiaceae family, especially the genera Kielmeyera and Clusia, are likely to be major sources of geopropolis produced by M. scutellaris. PMID:26544117

A new ester coumarin from Ferula Persica wild, indigenous to Iran.

PubMed

Razavi, Seyed Mehdi; Janani, Mehrnoush

2015-01-01

Ferula persica wild (Apiaceae) is a perennial herb indigenous to Iran. It has been used in folk medicine for treatment of diabetes, lowering of blood pressure and for antispasmodic, carminative, laxative and expectorant effects in central Iran. Dried ground roots of F. persica (150 g) were extracted sequentially with n-hexane, dichloromethane and methanol (MeOH), 500 ml each, using a Soxhlet apparatus. The n-hexane extract of the roots (3 g) was subjected to vacuum liquid chromatography on silica gel, eluting with solvent mixtures of increasing polarity: 100% n-hexane-ethyl acetate (EtOAc), to yield a number of fractions, Fraction 4 (80% EtOAc in n-hexane) was further analysed by preparative TLC (mobile phase was 12% acetone in chloroform) to yield a coumarin ester (10.1 mg, Rf = 0.31, blue florescent). The structure of the isolated compound was elucidated by spectroscopic means. The compound is 7-O-(4,8,12 -trihydroxy-4,8,12-trimethyl-tridecanoyl)-coumarin, named, ferulone C as a new natural product.

Synthesis and application of a highly selective copper ions fluorescent probe based on the coumarin group

NASA Astrophysics Data System (ADS)

He, Guangjie; Liu, Xiangli; Xu, Jinhe; Ji, Liguo; Yang, Linlin; Fan, Aiying; Wang, Songjun; Wang, Qingzhi

2018-02-01

A highly selective copper ions fluorescent probe based on the coumarin-type Schiff base derivative 1 (probe) was produced by condensation reaction between coumarin carbohydrazide and 1H-indazole-3-carbaldehyde. The UV-vis spectroscopy showed that the maximum absorption peak of compound 1 appeared at 439 nm. In the presence of Cu2 + ions, the maximum peak decreased remarkably compared with other physiological important metal ions and a new absorption peak at 500 nm appeared. The job's plot experiments showed that complexes of 1:2 binding mode were formed in CH3CN:HEPES (3:2, v/v) solution. Compound 1 exhibited a strong blue fluorescence. Upon addition of copper ions, the fluorescence gradually decreased and reached a plateau with the fluorescence quenching rate up to 98.73%. The detection limit for Cu2 + ions was estimated to 0.384 ppm. Fluorescent microscopy experiments demonstrated that probe 1 had potential to be used to investigate biological processes involving Cu2 + ions within living cells.

Determination of ground and excited state dipole moments of dipolar laser dyes by solvatochromic shift method.

PubMed

Patil, S K; Wari, M N; Panicker, C Yohannan; Inamdar, S R

2014-04-05

The absorption and fluorescence spectra of three medium sized dipolar laser dyes: coumarin 478 (C478), coumarin 519 (C519) and coumarin 523 (C523) have been recorded and studied comprehensively in various solvents at room temperature. The absorption and fluorescence spectra of C478, C519 and C523 show a bathochromic and hypsochromic shifts with increasing solvent polarity indicate that the transitions involved are π→π(∗) and n→π(∗). Onsager radii determined from ab initio calculations were used in the determination of dipole moments. The ground and excited state dipole moments were evaluated by using solvatochromic correlations. It is observed that the dipole moment values of excited states (μe) are higher than corresponding ground state values (μg) for the solvents studied. The ground and excited state dipole moments of these probes computed from ab initio calculations and those determined experimentally are compared and the results are discussed. Copyright © 2013 Elsevier B.V. All rights reserved.

6,7-dimethoxy-coumarin as a probe of hydration dynamics in biologically relevant systems

NASA Astrophysics Data System (ADS)

Ghose, Avisek; Amaro, Mariana; Kovaricek, Petr; Hof, Martin; Sykora, Jan

2018-04-01

Coumarin derivatives are well known fluorescence reporters for investigating biological systems due to their strong micro-environment sensitivity. Despite having wide range of environment sensitive fluorescence probes, the potential of 6,7-dimethoxy-coumarin has not been studied extensively so far. With a perspective of its use in protein studies, namely using the unnatural amino acid technology or as a substrate for hydrolase enzymes, we study acetyloxymethyl-6,7-dimethoxycoumarin (Ac-DMC). We investigate the photophysics and hydration dynamics of this dye in aerosol-OT (AOT) reverse micelles at various water contents using the time dependent fluorescence shift (TDFS) method. The TDFS response in AOT reverse micelles from water/surfactant ratio of 0 to 20 confirms its sensitivity towards the hydration and mobility of its microenvironment. Moreover, we show that the fluorophore can be efficiently quenched by halide ions. Hence, we conclude that the 6,7-dimethoxy-methylcoumarin fluorophore is useful for studying hydration parameters in biologically relevant systems.

Synthesis, characterization, crystal structure and quantum chemical investigations of three novel coumarin-benzenesulfonohydrazide derivatives

NASA Astrophysics Data System (ADS)

Chethan Prathap, K. N.; Lokanath, N. K.

2018-04-01

Coumarin derivatives are an important class of heterocyclic compounds due to their physical and biological properties. Coumarin derivatives have been identified with many significant electro-optical properties and biological activities. Three novel coumarin derivatives containing benzene sulfonohydrazide group were synthesized by condensation reaction. The synthesized compounds were characterized by various spectroscopic techniques (Mass, 1H/13C NMR and FTIR). Thermal and optical properties were investigated by thermogravimetric analysis (TGA), differential scanning calorimetry (DSC) and UV-Vis spectroscopic studies. Finally their structures were confirmed by single crystal X-ray diffraction (XRD) studies. The three compounds exhibit diverse intermolecular interactions, as observed by the crystal packing and Hirshfeld surface analysis. Further, their structures were optimized by density functional theory (DFT) calculations using B3LYP hybrid functionals with 6-311G+(d,p) level basis set. The Mulliken charge, molecular electrostatic potential (MEP), frontier molecular orbitals (HOMO-LUMO) were investigated. The experimentally determined parameters were compared with those calculated theoretically and they complement each other with a very good correlation. The transitions among the molecular orbitals were investigated using time-dependent density functional theory (TD-DFT) and the electronic absorption spectra obtained showed very good agreement with the experimentally measured UV-Vis spectra. Furthermore, non-linear optical (NLO) properties were investigated by calculating polarizabilities and hyperpolarizabilities. All three compounds exhibit significantly high hyperpolarizabilities compared to the reference material urea, which makes them potential candidates for NLO applications.

Writing and erasing hidden optical information on covalently modified cellulose paper.

PubMed

d'Halluin, M; Rull-Barrull, J; Le Grognec, E; Jacquemin, D; Felpin, F-X

2016-06-08

An unprecedented strategy for preparing photoresponsive cellulose paper enabling the storage of short-lived optical data by covalent photopatterning is disclosed. An ab initio design hinting that the covalent grafting of coumarins on the paper could yield valuable photoresponsive units was first performed. Second, light sensitive paper that can be reversibly altered upon irradiation at a specific wavelength was prepared by covalent surface functionalization with coumarins. Third, the validity of this strategy is demonstrated using the photolithography of several gripping patterns such as a dynamic QR code.

HPLC-DAD-MS identification of bioactive secondary metabolites from Ferula communis roots.

PubMed

Arnoldi, Lolita; Ballero, Mauro; Fuzzati, Nicola; Maxia, Andrea; Mercalli, Enrico; Pagni, Luca

2004-06-01

A simple HPLC method was developed to distinguish between 'poisonous' and 'non-poisonous' chemotypes of Ferula communis. The method was performed on a C8 reverse phase analytical column using a binary eluent (aqueous TFA 0.01%-TFA 0.01% in acetonitrile) under gradient condition. The two chemotypes showed different fingerprints. The identification of five coumarins and eleven daucane derivatives by HPLC-diode array detection (HPLC-DAD) and HPLC-MS is described. A coumarin, not yet described, was detected. Copyright 2004 Elsevier B.V.

Solvent organization around the perfluoro group of coumarin 153 governs its photophysical properties: An experimental and simulation study of coumarin dyes in ethanol as well as fluorinated ethanol solvents.

PubMed

Mondal, Saptarsi; Halder, Ritaban; Biswas, Biswajit; Jana, Biman; Singh, Prashant Chandra

2016-05-14

The self-aggregation property of the perfluoro group containing molecules makes it important in the research fields of biology and polymer and organic synthesis. In the quest of understanding the role of the perfluoro group on the photophysical properties of perfluoro-containing molecules in biologically important fluoroethanol solvents, we have applied photophysical as well as molecular dynamics simulation techniques to explore the properties of perfluoro groups containing molecule coumarin-153 (C153) in ethanol (ETH), monofluoroethanol (MFE), difluoroethanol (DFE), and trifluoroethanol (TFE) and compared them with the molecules without perfluoro moiety, namely coumarin-6H (C6H) and coumarin-480 (C480). In contrast to C6H and C480, the excited state lifetime of C153 in fluorinated ETHs is not monotonic. The excited state lifetime of C153 decreases in MFE and DFE as compared to ETH, whereas in TFE, it increases as compared to MFE and DFE. Molecular dynamics simulation reveals that the carbon terminal away from the OH group of fluorinated ETHs has a preferential orientation near the perfluoro (CF3) group of C153. In MFE and DFE, the CF3 group of C153 prefers to have a CF2-F⋯H -(CHF) type of electrostatic interaction over CF2-F⋯F -(CH2) kind of dispersion interaction which increases the rate of nonradiative decay, probably due to the electrostatic nature of the CF2-F⋯H -(CHF) hydrogen bond. On the other hand, in TFE, C-F⋯ F-C type of dispersion interaction, also known as fluorous interaction, takes place between the CF3 groups of C153 and TFE which decreases the rate of nonradiative rate as compared to MFE and DFE, leading to the increased lifetime of C153 in TFE. Photophysical and MD simulation studies clearly depict that the structural organization of solvents and their interaction with the fluorocarbon group are crucial factors for the photophysical behavior of the fluorocarbon containing molecules.

Solvent organization around the perfluoro group of coumarin 153 governs its photophysical properties: An experimental and simulation study of coumarin dyes in ethanol as well as fluorinated ethanol solvents

NASA Astrophysics Data System (ADS)

Mondal, Saptarsi; Halder, Ritaban; Biswas, Biswajit; Jana, Biman; Singh, Prashant Chandra

2016-05-01

The self-aggregation property of the perfluoro group containing molecules makes it important in the research fields of biology and polymer and organic synthesis. In the quest of understanding the role of the perfluoro group on the photophysical properties of perfluoro-containing molecules in biologically important fluoroethanol solvents, we have applied photophysical as well as molecular dynamics simulation techniques to explore the properties of perfluoro groups containing molecule coumarin-153 (C153) in ethanol (ETH), monofluoroethanol (MFE), difluoroethanol (DFE), and trifluoroethanol (TFE) and compared them with the molecules without perfluoro moiety, namely coumarin-6H (C6H) and coumarin-480 (C480). In contrast to C6H and C480, the excited state lifetime of C153 in fluorinated ETHs is not monotonic. The excited state lifetime of C153 decreases in MFE and DFE as compared to ETH, whereas in TFE, it increases as compared to MFE and DFE. Molecular dynamics simulation reveals that the carbon terminal away from the OH group of fluorinated ETHs has a preferential orientation near the perfluoro (CF3) group of C153. In MFE and DFE, the CF3 group of C153 prefers to have a CF2—F⋯H —(CHF) type of electrostatic interaction over CF2—F⋯F —(CH2) kind of dispersion interaction which increases the rate of nonradiative decay, probably due to the electrostatic nature of the CF2—F⋯H —(CHF) hydrogen bond. On the other hand, in TFE, C—F⋯ F—C type of dispersion interaction, also known as fluorous interaction, takes place between the CF3 groups of C153 and TFE which decreases the rate of nonradiative rate as compared to MFE and DFE, leading to the increased lifetime of C153 in TFE. Photophysical and MD simulation studies clearly depict that the structural organization of solvents and their interaction with the fluorocarbon group are crucial factors for the photophysical behavior of the fluorocarbon containing molecules.

High-performance liquid chromatography determination and pharmacokinetics of coumarin compounds after oral administration of Samul-Tang to rats.

PubMed

Hwang, Youn-Hwan; Cho, Won-Kyung; Jang, Doorye; Ha, Jeong-Ho; Ma, Jin Yeul

2014-01-01

Samul-tang has been traditionally used for the treatment of cardiovascular, gynecologic, cutaneous, and chronic inflammation disorders. Although coumarin compounds do have various pharmacological activities and the same may be present in Samul-tang, however there is little information about it. A simple and sensitive high-performance liquid chromatography (HPLC) method has been developed for the determination of nodakenin, nodakenetin, decursin, decursinol, and decursinol angelate in rat plasma. To obtain a better understanding for pharmacological properties of Samul-tang, pharmacokinetic study of coumarin compounds was performed after oral administration of Samul-tang in rats. Chromatographic separation of the analytes was successfully achieved on a Phenomenex Luna C18 column (4.6 mm×250 mm, 5 μm) using a mobile phase composed of acetonitrile water with a gradient elution at a flow rate of 1 mL/min. Noncompartmental analysis was performed. Calibration curves for all analytes had good linearity (r(2) <0.999) in a wide linear range. The lower limit of quantification (LLOQ) ranged from 0.05 to 0.1 μg/mL. The variation of intra- and interday assay was less than 15%. Nodakenin, nodakenetin, and decursinol were determined in rat plasma after oral administration of Samul-tang. This developed and validated HPLC method was successfully applied to the pharmacokinetic study of three coumarin compounds in rats, given as a single oral administration of Samul-tang. These pharmacokinetic data of the nodakenin, nodakenetin, and decursinol could offer a new point of view to evaluate the pharmacological effects of Samul-tang.

Synthesis of bifunctional molecules containing [12]aneN3 and coumarin moieties as effective DNA condensation agents and new non-viral gene vectors.

PubMed

Yue, Pan; Zhang, Ying; Guo, Zhi-Fo; Cao, Ao-Cheng; Lu, Zhong-Lin; Zhai, Yong-Gong

2015-04-21

A series of bifunctional molecules with different combinations of macrocyclic polyamine [12]aneN3 and coumarin moieties, 4a/b and 5a/b, were synthesized by a two-step copper(I)-mediated alkyne–azide click reactions between 1,3,5-tris(azidomethyl)benzene and Boc-protected N-propynyl-[12]aneN3/7-propynyloxycoumarins. Agarose gel electrophoresis experiments indicated that bifunctional molecules 4b and 5b effectively induced complete plasmid DNA condensation at concentrations up to 40 μM. It was found that the structural variation had a major impact on the condensation behavior of these compounds. The electrostatic interaction involving the [12]aneN3 moiety can be compensated by the binding contribution of the coumarin units during the DNA condensation process. These two types of interaction showed different effects on the reversibility of DNA condensation. Results from studies using dynamic laser scattering, atomic force microscopy, and EB replacement assay further supported the above conclusion. Cytotoxicity assays on bifunctional compounds 4a/b and 5a/b indicated their low cytotoxicity. Results from cellular uptake and cell transfection experiments proved that bifunctional compounds 4b and 5b successfully served as non-viral gene vectors. Furthermore, methyl substituents attached to the coumarin unit (4b and 5b) greatly enhanced their DNA condensation capability and gene transfection. These bifunctional molecules, with the advantages of lower cytotoxicity, good water solubility, and potential structural modification, will have great potential for the development of new non-viral gene delivery agents.

Convergence of Free Energy Profile of Coumarin in Lipid Bilayer

PubMed Central

2012-01-01

Atomistic molecular dynamics (MD) simulations of druglike molecules embedded in lipid bilayers are of considerable interest as models for drug penetration and positioning in biological membranes. Here we analyze partitioning of coumarin in dioleoylphosphatidylcholine (DOPC) bilayer, based on both multiple, unbiased 3 μs MD simulations (total length) and free energy profiles along the bilayer normal calculated by biased MD simulations (∼7 μs in total). The convergences in time of free energy profiles calculated by both umbrella sampling and z-constraint techniques are thoroughly analyzed. Two sets of starting structures are also considered, one from unbiased MD simulation and the other from “pulling” coumarin along the bilayer normal. The structures obtained by pulling simulation contain water defects on the lipid bilayer surface, while those acquired from unbiased simulation have no membrane defects. The free energy profiles converge more rapidly when starting frames from unbiased simulations are used. In addition, z-constraint simulation leads to more rapid convergence than umbrella sampling, due to quicker relaxation of membrane defects. Furthermore, we show that the choice of RESP, PRODRG, or Mulliken charges considerably affects the resulting free energy profile of our model drug along the bilayer normal. We recommend using z-constraint biased MD simulations based on starting geometries acquired from unbiased MD simulations for efficient calculation of convergent free energy profiles of druglike molecules along bilayer normals. The calculation of free energy profile should start with an unbiased simulation, though the polar molecules might need a slow pulling afterward. Results obtained with the recommended simulation protocol agree well with available experimental data for two coumarin derivatives. PMID:22545027

Convergence of Free Energy Profile of Coumarin in Lipid Bilayer.

PubMed

Paloncýová, Markéta; Berka, Karel; Otyepka, Michal

2012-04-10

Atomistic molecular dynamics (MD) simulations of druglike molecules embedded in lipid bilayers are of considerable interest as models for drug penetration and positioning in biological membranes. Here we analyze partitioning of coumarin in dioleoylphosphatidylcholine (DOPC) bilayer, based on both multiple, unbiased 3 μs MD simulations (total length) and free energy profiles along the bilayer normal calculated by biased MD simulations (∼7 μs in total). The convergences in time of free energy profiles calculated by both umbrella sampling and z-constraint techniques are thoroughly analyzed. Two sets of starting structures are also considered, one from unbiased MD simulation and the other from "pulling" coumarin along the bilayer normal. The structures obtained by pulling simulation contain water defects on the lipid bilayer surface, while those acquired from unbiased simulation have no membrane defects. The free energy profiles converge more rapidly when starting frames from unbiased simulations are used. In addition, z-constraint simulation leads to more rapid convergence than umbrella sampling, due to quicker relaxation of membrane defects. Furthermore, we show that the choice of RESP, PRODRG, or Mulliken charges considerably affects the resulting free energy profile of our model drug along the bilayer normal. We recommend using z-constraint biased MD simulations based on starting geometries acquired from unbiased MD simulations for efficient calculation of convergent free energy profiles of druglike molecules along bilayer normals. The calculation of free energy profile should start with an unbiased simulation, though the polar molecules might need a slow pulling afterward. Results obtained with the recommended simulation protocol agree well with available experimental data for two coumarin derivatives.

Localization and pattern of graviresponse across the pulvinus of barley Hordeum vulgare

NASA Technical Reports Server (NTRS)

Brock, T. G.; Lu, C. R.; Ghosheh, N. S.; Kaufman, P. B.

1989-01-01

Pulvini of excised stem segments from barley (Hordeum vulgare cv Larker') were pretreated with 1 millimolar coumarin before gravistimulation to reduce longitudinal cell expansion and exaggerate radial cell enlargement. The cellular localization and pattern of graviresponse across individual pulvini were then evaluated by cutting the organ in cross-section, photographing the cross-section, and then measuring pulvinus thickness and the radial width of cortical and epidermal cells in enlargements of the photomicrographs. With respect to orientation during gravistimulation, we designated the uppermost point of the cross-section 0 degrees and the lowermost point 180 degrees. A gravity-induced increase in pulvinus thickness was observable within 40 degrees of the vertical in coumarin-treated pulvini. In upper halves of coumarin-treated gravistimulated pulvini, cells in the inner cortex and inner epidermis had increased radial widths, relative to untreated gravistimulated pulvini. In lower halves of coumarin-treated pulvini, cells in the central and outer cortex and in the outer epidermis showed the greatest increase in radial width. Cells comprising the vascular bundles also increased in radial width, with this pattern following that of the central cortex. These results indicate (a) that all cell types are capable of showing a graviresponse, (b) that the graviresponse occurs in both the top and the bottom of the responding organ, and (c) that the magnitude of the response increases approximately linearly from the uppermost point to the lowermost. These results are also consistent with models of gravitropism that link the pattern and magnitude of the graviresponse to graviperception via statolith sedimentation.

Gas-Phase Structures of Linalool and Coumarin Studied by Microwave Spectroscopy

NASA Astrophysics Data System (ADS)

Nguyen, H. V. L.; Stahl, W.; Grabow, J.-U.

2013-06-01

The microwave spectra of two natural substances, linalool and coumarin, were recorded in the microwave range from 9 to 16 GHz and 8.5 to 10.5 GHz, respectively.Linalool is an acyclic monoterpene and the main component of lavender oil. It has a structure with many possible conformations. The geometry of the lowest energy conformer has been determined by a combination of microwave spectroscopy and quantum chemical calculations. Surprisingly, a globular rather than a prolate shape was found. This structure is probably stabilized by a π interaction between two double bonds which are arranged in two stacked layers of atoms within the molecule. A-E splittings due to the internal rotation of one methyl group could be resolved and the barrier to internal rotation was determined to be 400.20(64) cm^{-1}. The standard deviation of the fit was close to experimental accuracy. For an identification of the observed conformer not only the rotational constants but also the internal rotation parameters of one of the methyl groups were needed. Coumarin is a widely used flavor in perfumery as sweet woodruff scent. The aromatic structure allows solely for one planar conformer, which was found under molecular beam conditions and compared to other molecules with similar structures. Here, the rotational spectrum could be described by a set of parameters including the rotational constants and the centrifugal distortion constants using a semi-rigid molecule Hamiltonian. Furthermore, the rotational transitions of all nine ^{13}C isotopologues were measured in natural abundance. As a consequence, the microwave structure of coumarin could be almost completely determined.

Immunosuppressive Activity of Daphnetin, One of Coumarin Derivatives, Is Mediated through Suppression of NF-κB and NFAT Signaling Pathways in Mouse T Cells

PubMed Central

Liu, Yan; Xu, Sisi; Huang, Guoren; Xiong, Ying; Zhang, Shuang; Xu, Linli; Deng, Xuming; Guan, Shuang

2014-01-01

Daphnetin, a plant-derived dihydroxylated derivative of coumarin, is an effective compound extracted from a plant called Daphne Korean Nakai. Coumarin derivates were known for their antithrombotic, anti-inflammatory, and antioxidant activities. The present study was aimed to determine the immunosuppressive effects and the underlying mechanisms of daphnetin on concanavalin A (ConA) induced T lymphocytes in mice. We showed that, in vitro, daphnetin suppressed ConA-induced splenocyte proliferation, influenced production of the cytokines and inhibited cell cycle progression through the G0/G1 transition. The data also revealed that daphnetin could down-regulate activation of ConA induced NF-κB and NFAT signal transduction pathways in mouse T lymphocyte. In vivo, daphnetin treatment significantly inhibited the 2, 4- dinitrofluorobenzene (DNFB) -induced delayed type hypersensitivity (DTH) reactions in mice. Collectively, daphnetin had strong immunosuppressive activity both in vitro and in vivo, suggesting a potential role for daphnetin as an immunosuppressive agent, and established the groundwork for further research on daphnetin. PMID:24800925

Coumarin-gold nanoparticle bioconjugates: preparation, antioxidant, and cytotoxic effects against MCF-7 breast cancer cells

NASA Astrophysics Data System (ADS)

Mahendran, Gokila; Ponnuchamy, Kumar

2018-05-01

In recent, the conjugation of gold nanoparticles (AuNPs) with biomolecules has shown great potential especially in disease diagnostics and treatment. Taking this in account, we report the methodology involved in the conjugation of coumarin onto the surface of citrate-capped AuNPs by a simple in situ method. Herein, we systematically performed UV-Vis spectroscopy, transmission electron microscopy, dynamic light scattering, and zeta potential measurements to characterize citrate-capped AuNPs and bioconjugates. Our results demonstrate in-depth surface chemistry of bioconjugates with improved surface plasmon resonance (529 nm), morphology (near spherical shape), hydrodynamic diameter (25.3 nm) as well as surface charge (- 35 mV). Furthermore, the bioconjugates displayed dose-dependent response in scavenging free radicals and exhibited cytotoxicity against MCF-7 breast cancer cell lines. In addition, phase-contrast microscopic analysis revealed that bioconjugates promote apoptosis in cancer cells in a time-dependent manner. Overall, we ascertain the fact that this kind of bioconjugation of AuNPs with coumarin further enhances the efficacy of inorganic nanomaterials and thus make them a better bio-therapeutic candidate.

Theoretical Design of a Two-Photon Fluorescent Probe for Nitric Oxide with Enhanced Emission Induced by Photoninduced Electron Transfer.

PubMed

Zhang, Yujin; Leng, Jiancai; Hu, Wei

2018-04-25

In the present work, we systematically investigate the sensing abilities of two recently literature-reported two-photon fluorescent NO probes, i.e., the o-phenylenediamine derivative of Nile Red and the p-phenylenediamine derivative of coumarin. The recognition mechanisms of these probes are studied by using the molecular orbital classifying method, which demonstrates the photoinduced electron transfer process. In addition, we have designed two new probes by swapping receptor units present on fluorophores, i.e., the p-phenylenediamine derivative of Nile Red and the o-phenylenediamine derivative of coumarin. However, it illustrates that only the latter has ability to function as off-on typed fluorescent probe for NO. More importantly, calculations on the two-photon absorption properties of the probes demonstrate that both receptor derivatives of coumarin possess larger TPA cross-sections than Nile Red derivatives, which makes a better two photon fluorescent probe. Our theoretical investigations reveal that the underlying mechanism satisfactorily explain the experimental results, providing a theoretical basis on the structure-property relationships which is beneficial to developing new two-photon fluorescent probes for NO.

New coumarin derivative as an eco-friendly inhibitor of corrosion of mild steel in Acid medium.

PubMed

Al-Amiery, Ahmed A; Al-Majedy, Yasameen K; Kadhum, Abdul Amir H; Mohamad, Abu Bakar

2014-12-29

The anticorrosion ability of a synthesized coumarin, namely 2-(coumarin-4-yloxy)acetohydrazide (EFCI), for mild steel (MS) in 1 M hydrochloric acid solution has been studied using a weight loss method. The effect of temperature on the corrosion rate was investigated, and some thermodynamic parameters were calculated. The results indicated that inhibition efficiencies were enhanced with an increase in concentration of inhibitor and decreased with a rise in temperature. The IE value reaches 94.7% at the highest used concentration of the new eco-friendly inhibitor. The adsorption of inhibitor on MS surface was found to obey a Langmuir adsorption isotherm. Scanning electron microscopy (SEM) was performed on inhibited and uninhibited mild steel samples to characterize the surface. The Density Function theory (DFT) was employed for quantum-chemical calculations such as EHOMO (highest occupied molecular orbital energy), ELUMO (lowest unoccupied molecular orbital energy) and μ (dipole moment), and the obtained results were found to be consistent with the experimental findings. The synthesized inhibitor was characterized by Fourier transform infrared (FTIR) and nuclear magnetic resonance (NMR) spectroscopic studies.

Coumarin based colorimetric and fluorescence on-off chemosensor for F-, CN- and Cu2 + ions

NASA Astrophysics Data System (ADS)

Roy, Debashis; Chakraborty, Arijit; Ghosh, Rina

2018-02-01

(E)-4-Chloro-3-[{2-(4-nitrophenyl)hydrazono}methyl]-2H-chromen-2-one (C), a coumarin derivative has been studied toward its ion sensing properties for F-, CN- and Cu2 +. A proton-transfer mechanism for F- sensing has been deduced with the help of 1H NMR titration alongwith from the changes in the absorption and emission spectra of C in the presence of F-. C formed 1:1 stoichiometric complex with each of these analytes. Sensing of C toward Cu2 + is poor, but interestingly in the presence of F- or CN- the sensing ability of Cu2 + gets enhanced many folds, and C can act as F- or CN- mediated off-on sensor for Cu2 +. Moreover, colorimetric strip (pre-coated with the coumarin derived compound) tests for F- and CN- from their DMSO solution at high temperature ( 100 °C) opens up the door for easiest naked eye recognition and distinction of these ions, and also for naked-eye detection of F- and CN- from its aqueous solution at high temperature ( 100 °C).

Total synthesis of 8-(6″-umbelliferyl)-apigenin and its analogs as anti-diabetic reagents.

PubMed

Pan, Guojun; Zhao, Lianbo; Xiao, Na; Yang, Ke; Ma, Yantao; Zhao, Xia; Fan, Zhenchuan; Zhang, Yongmin; Yao, Qingwei; Lu, Kui; Yu, Peng

2016-10-21

The naturally occurring flavone 8-(6″-umbelliferyl)apigenin, a hybrid structure of apigenin and coumarin, as well as seven of its analogues were synthesized for the first time by using iodination and Suzuki coupling reactions as key steps. The synthesis of 8-(6″-umbelliferyl)-apigenin was achieved in seven linear steps from the commercially available 1-(2,4,6-trihydroxyphenyl)ethan-1-one and 7-hydroxyl coumarine with 31% overall yield. Effects of these compounds on glucose disposal were investigated in adipocytes. All of the flavonoid and coumarin hydrids were found to have better bioactivities than their corresponding flavonoid cores. The most potent compound 15 (10 μΜ) could promote glucose consumption by 57% which exhibited similar effect as the positive control metformin at 1 mM. Moreover, fluorescence microscopy showed that four 8-(6″-umbelliferyl)apigenin analogues 2, 15, 30 and 31 could promote the 2-NBDG uptake into 3T3-L1 cells, which consist with those observed in the regulation of glucose. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Green Chromatographic Separation of Coumarin and Vanillins Using Subcritical Water as the Mobile Phase.

PubMed

Kayan, Berkant; Akay, Sema; Yang, Yu

2016-08-01

Pure water was used as the eluent for separation of coumarin, vanillin and ethyl vanillin at temperatures ranging from 100 to 200°C using a homemade subcritical water chromatography (SBWC) system. Chromatographic separations were performed on five commercial columns including XTerra MS C18, XBridge C18, Zorbax RRHD Eclipse Plus, Zorbax SB-Phenyl and Zorbax SB-C18 columns. The retention time of all three solutes decreased with increasing water temperature. The shortest retention time among all acceptable separations, less than 4 min, was achieved on the Zorbax SB-C18 column at 200°C. While separations on the XTerra MS C18 column resulted in fronting peaks and a degradation peak from ethyl vanillin on the Zorbax RRHD Eclipse Plus column was observed, all three other columns yielded reasonable separations under SBWC conditions. In addition to separation of the standard test mixture, separation of coumarin contained in a skincare cream sample was also carried out using SBWC. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Ultrafast hydrogen bond dynamics and partial electron transfer after photoexcitation of diethyl ester of 7-(diethylamino)-coumarin-3-phosphonic acid and its benzoxaphosphorin analog.

PubMed

Wagner, M S; Ilieva, E D; Petkov, P St; Nikolova, R D; Kienberger, R; Iglev, H

2015-04-21

The solvation dynamics after optical excitation of two phosphono-substituted coumarin derivatives dissolved in various solutions are studied by fluorescence up-conversion spectroscopy and quantum chemical simulations. The Kamlet-Taft analysis of the conventional absorption and emission spectra suggests weakening of the solvent-solute H-bonds upon optical excitation, which is in contrast to the results gained by the quantum simulations and earlier studies reported for coumarin derivatives without phosphono groups. The simulations give evidence that the solvent reorganisation around the excited fluorophore leads to partial electron transfer to the first solvation shell. The process occurs on a timescale between 1 and 10 ps depending on the solvent polarity and leads to a fast decay of the time-resolved emission signal. Using the ultrafast spectral shift of the time-dependent fluorescence we estimated the relaxation time of the H-bonds in the electronically excited state to be about 0.6 ps in water, 1.5 ps in ethanol and 2.8 ps in formamide.

Synthesis and evaluation of coumermycin A1 analogues that inhibit the Hsp90 protein folding machinery.

PubMed

Burlison, Joseph A; Blagg, Brian S J

2006-10-12

[structure: see text] The coumarin antibiotics are not only potent inhibitors of DNA gyrase but also represent the most effective C-terminal inhibitors of 90 kDa heat shock proteins (Hsp90) reported thus far. In contrast to the N-terminal ATP-binding site, little is known about the Hsp90 C-terminus. In addition, very limited structure-activity relationships exist between this class of natural products and Hsp90. In this letter, the syntheses of dimeric coumarin analogues are presented along with their inhibitory values in breast cancer cell lines.

The antiproliferative effect of coumarins on several cancer cell lines.

PubMed

Kawaii, S; Tomono, Y; Ogawa, K; Sugiura, M; Yano, M; Yoshizawa, Y

2001-01-01

Twenty-one coumarins were examined for their antiproliferative activity towards several cancer cell lines, namely lung carcinoma (A549), melanin pigment producing mouse melanoma (B16 melanoma 4A5), human T-cell leukemia (CCRF-HSB-2), and human gastric cancer, lymph node metastasized (TGBC11TKB). The structure-activity relationship established from the results revealed that the 6,7-dihydroxy moiety had an important role for their antiproliferative activity. Analysis of cell cycle distribution indicated that esculetin-treated cells accumulated in the G1 (at 400 microM) or in S phase (at 100 microM).

Resonance energy transfer: Dye to metal nanoparticles

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

Wari, M. N.; Pujar, G. H.; Inamdar, S. R., E-mail: him-lax3@yahoo.com

2015-06-24

In the present study, surface energy transfer (SET) from Coumarin 540A (C540 A) to Gold nanoparticle (Au) is demonstrated. The observed results show pronounced effect on the photoluminescence intensity and shortening of the lifetime of Coumarin 540A upon interaction with the spherical gold nanoparticle, also there are measured effects on radiative rate of the dye. Experimental results are analyzed with fluorescence resonance energy transfer (FRET) and SET theories. The results obtained from distance-dependent quenching provide experimental evidence that the efficiency curve slope and distance of quenching is best modeled by surface energy transfer process.

Image storage in coumarin-based copolymer thin films by photoinduced dimerization.

PubMed

Gindre, Denis; Iliopoulos, Konstantinos; Krupka, Oksana; Champigny, Emilie; Morille, Yohann; Sallé, Marc

2013-11-15

We report a technique to encode grayscale digital images in thin films composed of copolymers containing coumarins. A nonlinear microscopy setup was implemented and two nonlinear optical processes were used to store and read information. A third-order process (two-photon absorption) was used to photoinduce a controlled dimer-to-monomer ratio within a defined tiny volume in the material, which corresponds to each recorded bit of data. Moreover, a second-order process (second-harmonic generation) was used to read the stored information, which has been found to be highly dependent upon the monomer-to-dimer ratio.

Cytotoxic activity and composition of petroleum ether extract from Magydaris tomentosa (Desf.) W. D. J. Koch (Apiaceae).

PubMed

Autore, Giuseppina; Marzocco, Stefania; Formisano, Carmen; Bruno, Maurizio; Rosselli, Sergio; Jemia, Mariem Ben; Senatore, Felice

2015-01-16

The petroleum ether extract of Magydaris tomentosa flowers (Desf.) W. D. J. Koch has been analyzed by GC-MS. It is mainly constituted by furanocoumarins such as xanthotoxin, xanthotoxol, isopimpinellin, and bergaptene. Other coumarins such as 7-methoxy-8-(2-formyl-2-methylpropyl) coumarin and osthole also occurred. The antiproliferative activity of Magydaris tomentosa flower extract has been evaluated in vitro on murine monocye/macrophages (J774A.1), human melanoma (A375) and human breast cancer (MCF-7) tumor cell lines, showing a major activity against the latter.

High-performance liquid chromatography determination and pharmacokinetics of coumarin compounds after oral administration of Samul-Tang to rats

PubMed Central

Hwang, Youn-Hwan; Cho, Won-Kyung; Jang, Doorye; Ha, Jeong-Ho; Ma, Jin Yeul

2014-01-01

Background: Samul-tang has been traditionally used for the treatment of cardiovascular, gynecologic, cutaneous, and chronic inflammation disorders. Although coumarin compounds do have various pharmacological activities and the same may be present in Samul-tang, however there is little information about it. Objective: A simple and sensitive high-performance liquid chromatography (HPLC) method has been developed for the determination of nodakenin, nodakenetin, decursin, decursinol, and decursinol angelate in rat plasma. To obtain a better understanding for pharmacological properties of Samul-tang, pharmacokinetic study of coumarin compounds was performed after oral administration of Samul-tang in rats. Materials and Methods: Chromatographic separation of the analytes was successfully achieved on a Phenomenex Luna C18 column (4.6 mm×250 mm, 5 μm) using a mobile phase composed of acetonitrile water with a gradient elution at a flow rate of 1 mL/min. Noncompartmental analysis was performed. Results: Calibration curves for all analytes had good linearity (r2 <0.999) in a wide linear range. The lower limit of quantification (LLOQ) ranged from 0.05 to 0.1 μg/mL. The variation of intra- and interday assay was less than 15%. Nodakenin, nodakenetin, and decursinol were determined in rat plasma after oral administration of Samul-tang. Conclusion: This developed and validated HPLC method was successfully applied to the pharmacokinetic study of three coumarin compounds in rats, given as a single oral administration of Samul-tang. These pharmacokinetic data of the nodakenin, nodakenetin, and decursinol could offer a new point of view to evaluate the pharmacological effects of Samul-tang. PMID:24696544

Modulation of chaperone function and cochaperone interaction by novobiocin in the C-terminal domain of Hsp90: evidence that coumarin antibiotics disrupt Hsp90 dimerization.

PubMed

Allan, Rudi K; Mok, Danny; Ward, Bryan K; Ratajczak, Thomas

2006-03-17

The C-terminal domain of Hsp90 displays independent chaperone activity, mediates dimerization, and contains the MEEVD motif essential for interaction with tetratricopeptide repeat-containing immunophilin cochaperones assembled in mature steroid receptor complexes. An alpha-helical region, upstream of the MEEVD peptide, helps form the dimerization interface and includes a hydrophobic microdomain that contributes to the Hsp90 interaction with the immunophilin cochaperones and corresponds to the binding site for novobiocin, a coumarin-related Hsp90 inhibitor. Mutation of selected residues within the hydrophobic microdomain significantly impacted the chaperone function of a recombinant C-terminal Hsp90 fragment and novobiocin inhibited wild-type chaperone activity. Prior incubation of the Hsp90 fragment with novobiocin led to a direct blockade of immunophilin cochaperone binding. However, the drug had little influence on the pre-formed Hsp90-immunophilin complex, suggesting that bound cochaperones mask the novobiocin-binding site. We observed a differential effect of the drug on Hsp90-immunophilin interaction, suggesting that the immunophilins make distinct contacts within the C-terminal domain to specifically modulate Hsp90 function. Novobiocin also precluded the interaction of full-length Hsp90 with the p50(cdc37) cochaperone, which targets the N-terminal nucleotide-binding domain, and is prevalent in Hsp90 complexes with protein kinase substrates. Novobiocin therefore acts locally and allosterically to induce conformational changes within multiple regions of the Hsp90 protein. We provide evidence that coumermycin A1, a coumarin structurally related to novobiocin, interferes with dimerization of the Hsp90 C-terminal domain. Coumarin-based inhibitors then may antagonize Hsp90 function by inducing a conformation favoring separation of the C-terminal domains and release of substrate.

Screening of Six Medicinal Plant Extracts Obtained by Two Conventional Methods and Supercritical CO₂ Extraction Targeted on Coumarin Content, 2,2-Diphenyl-1-picrylhydrazyl Radical Scavenging Capacity and Total Phenols Content.

PubMed

Molnar, Maja; Jerković, Igor; Suknović, Dragica; Bilić Rajs, Blanka; Aladić, Krunoslav; Šubarić, Drago; Jokić, Stela

2017-02-24

Six medicinal plants Helichrysum italicum (Roth) G. Don, Angelica archangelica L., Lavandula officinalis L., Salvia officinalis L., Melilotus officinalis L., and Ruta graveolens L. were used. The aim of the study was to compare their extracts obtained by Soxhlet (hexane) extraction, maceration with ethanol (EtOH), and supercritical CO₂ extraction (SC-CO₂) targeted on coumarin content (by high performance liquid chromatography with ultraviolet detection, HPLC-UV), 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) scavenging capacity, and total phenols (TPs) content (by Folin-Ciocalteu assay). The highest extraction yields were obtained by EtOH, followed by hexane and SC-CO₂. The highest coumarin content (316.37 mg/100 g) was found in M. officinalis EtOH extracts, but its SC-CO₂ extraction yield was very low for further investigation. Coumarin was also found in SC-CO₂ extracts of S. officinalis , R. graveolens , A. archangelica , and L. officinalis . EtOH extracts of all plants exhibited the highest DPPH scavenging capacity. SC-CO₂ extracts exhibited antiradical capacity similar to hexane extracts, while S. officinalis SC-CO₂ extracts were the most potent (95.7%). EtOH extracts contained the most TPs (up to 132.1 mg gallic acid equivalents (GAE)/g from H. italicum ) in comparison to hexane or SC-CO₂ extracts. TPs content was highly correlated to the DPPH scavenging capacity of the extracts. The results indicate that for comprehensive screening of different medicinal plants, various extraction techniques should be used in order to get a better insight into their components content or antiradical capacity.

Lipophilicity plays a major role in modulating the inhibition of monoamine oxidase B by 7-substituted coumarins.

PubMed

Carotti, Angelo; Altomare, Cosimo; Catto, Marco; Gnerre, Carmela; Summo, Luciana; De Marco, Agostino; Rose, Sarah; Jenner, Peter; Testa, Bernard

2006-02-01

A series of coumarin derivatives (1-22), bearing at the 7-position ether, ketone, ester, carbamate, or amide functions of varying size and lipophilicity, were synthesized and investigated for their in vitro monoamine oxidase-A and -B (MAO-A and -B) inhibitory activities. Most of the compounds acted preferentially as MAO-B inhibitors, with IC(50) values in the micromolar to low-nanomolar range. A structure-activity-relationship (SAR) study highlighted lipophilicity as an important property modulating the MAO-B inhibition potency of 7-substituted coumarins, as shown by a linear correlation (n=20, r(2)=0.72) between pIC(50) and calculated log P values. The stability of ester-containing coumarin derivatives in rat plasma provided information on factors that either favor (lipophilicity) or decrease (steric hindrance) esterase-catalyzed hydrolysis. Two compounds (14 and 22) were selected to investigate how lipophilicity and enzymatic stability may affect in vivo MAO activities, as assayed ex vivo in rat. The most-potent and -selective MAO-B inhibitor 22 (=7-[(3,4-difluorobenzyl)oxy]-3,4-dimethyl-1-benzopyran-2(2H)-one) within the examined series significantly inhibited (>60%) ex vivo rat-liver and striatal MAO-B activities 1 h after intraperitoneal administration of high doses (100 and 300 mumol kg(-1)), revealing its ability to cross the blood-brain barrier. At the same doses, liver and striatum MAO-A was less inhibited in vivo, somehow reflecting MAO-B selectivity, as assessed in vitro. In contrast, the metabolically less stable derivative 14, bearing an isopropyl ester in the lateral chain, had a weak effect on hepatic MAO-B activity in vivo, and none on striatal MAO-B, but, surprisingly, displayed inhibitory effects on MAO-A in both peripheral and brain tissues.

3D QSAR studies on binding affinities of coumarin natural products for glycosomal GAPDH of Trypanosoma cruzi

NASA Astrophysics Data System (ADS)

Menezes, Irwin R. A.; Lopes, Julio C. D.; Montanari, Carlos A.; Oliva, Glaucius; Pavão, Fernando; Castilho, Marcelo S.; Vieira, Paulo C.; Pupo, M.^onica T.

2003-05-01

Drug design strategies based on Comparative Molecular Field Analysis (CoMFA) have been used to predict the activity of new compounds. The major advantage of this approach is that it permits the analysis of a large number of quantitative descriptors and uses chemometric methods such as partial least squares (PLS) to correlate changes in bioactivity with changes in chemical structure. Because it is often difficult to rationalize all variables affecting the binding affinity of compounds using CoMFA solely, the program GRID was used to describe ligands in terms of their molecular interaction fields, MIFs. The program VolSurf that is able to compress the relevant information present in 3D maps into a few descriptors can treat these GRID fields. The binding affinities of a new set of compounds consisting of 13 coumarins, for one of which the three-dimensional ligand-enzyme bound structure is known, were studied. A final model based on the mentioned programs was independently validated by synthesizing and testing new coumarin derivatives. By relying on our knowledge of the real physical data (i.e., combining crystallographic and binding affinity results), it is also shown that ligand-based design agrees with structure-based design. The compound with the highest binding affinity was the coumarin chalepin, isolated from Rutaceae species, with an IC50 value of 55.5 μM towards the enzyme glyceraldehyde-3-phosphate dehydrogenase (gGAPDH) from glycosomes of the parasite Trypanosoma cruzi, the causative agent of Chagas' disease. The proposed models from GRID MIFs have revealed the importance of lipophilic interactions in modulating the inhibition, but without excluding the dependence on stereo-electronic properties as found from CoMFA fields.

A highly selective fluorescent probe based on coumarin for the imaging of N2H4 in living cells

NASA Astrophysics Data System (ADS)

Chen, Song; Hou, Peng; Wang, Jing; Liu, Lei; Zhang, Qi

2017-02-01

A turn-on fluorescence probe for highly sensitive and selective detection of N2H4 was developed based on hydrazine-triggered a substitution- cyclization-elimination cascade. Upon the treatment with N2H4, probe 1, 4-methyl-coumarin-7-yl bromobutanoate, displayed a remarkable fluorescence enhancement (25-fold) with a maximum at 450 nm. This probe can quantitatively detect N2H4 with a extremely low detection limit as 7 × 10- 8 M. Moreover, cell imaging experiments have indicated that probe 1 has potential ability to detect and image N2H4 in biological systems.

A novel coumarin Schiff-base as a Ni(II) ion colorimetric sensor

NASA Astrophysics Data System (ADS)

Wang, Lingyun; Ye, Decheng; Cao, Derong

2012-05-01

A novel coumarin Schiff base compound (L) prepared from 7-diethylaminocoumarin-3-aldehyde and 3-amino-7-hydroxycoumarin was synthesized and evaluated as a chemoselective Ni2+ sensor. Addition of Ni2+ to CH3CN solution of L resulted in a rapid color change from yellow to red together with a large red shift from 465 to 516 nm. Moreover, other common alkali-, alkaline earth-, transition- and rare earth metal ions induced no or minimal spectral changes. Experimental results indicated that L could be used as a potential Ni2+ colorimetric and naked-eye chemosensor in CH3CN solution.

Effect of viscosity on photoinduced electron transfer reaction: An observation of the Marcus inverted region in homogeneous solvents

NASA Astrophysics Data System (ADS)

Saini, Rajesh Kumar; Kuchlyan, Jagannath; Sarkar, Nilmoni

2016-09-01

The viscosity effect of homogeneous solvents on the dynamics of photoinduced electron transfer (PET) reaction among the coumarins and N,N-dimethylaniline (DMA) is investigated using steady-state and time-resolved fluorescence spectroscopy. A bell shape Marcus inversion in the ET rates has been detected in the plot of ET rate constant (kq) with free energy change (ΔG0) in viscous solvents decanol and EG, but it is not observed in DMSO like low viscous solvent. We have also reported that there is no complex formation between the coumarin dye and DMA molecule by using fluorescence correlation spectroscopy.

Quantum dynamical simulation of photoinduced electron transfer processes in dye-semiconductor systems: theory and application to coumarin 343 at TiO₂.

PubMed

Li, Jingrui; Kondov, Ivan; Wang, Haobin; Thoss, Michael

2015-04-10

A recently developed methodology to simulate photoinduced electron transfer processes at dye-semiconductor interfaces is outlined. The methodology employs a first-principles-based model Hamiltonian and accurate quantum dynamics simulations using the multilayer multiconfiguration time-dependent Hartree approach. This method is applied to study electron injection in the dye-semiconductor system coumarin 343-TiO2. Specifically, the influence of electronic-vibrational coupling is analyzed. Extending previous work, we consider the influence of Dushinsky rotation of the normal modes as well as anharmonicities of the potential energy surfaces on the electron transfer dynamics.

External and Intraparticle Diffusion of Coumarin 102 with Surfactant in the ODS-silica Gel/water System by Single Microparticle Injection and Confocal Fluorescence Microspectroscopy.

PubMed

Nakatani, Kiyoharu; Matsuta, Emi

2015-01-01

The release mechanism of coumarin 102 from a single ODS-silica gel microparticle into the water phase in the presence of Triton X-100 was investigated by confocal fluorescence microspectroscopy combined with the single microparticle injection technique. The release rate significantly depended on the Triton X-100 concentration in the water phase and was not limited by diffusion in the pores of the microparticle. The release rate constant was inversely proportional to the microparticle radius squared, indicating that the rate-determining step is the external diffusion between the microparticle and the water phase.

Chemistry and biological activity of coumarins at molecular level.

PubMed

Garro, Hugo A; García, Celina; Martín, Víctor S; Tonn, Carlos E; Pungitore, Carlos R

2014-08-01

Synthetic coumarins were prepared in high yields using ionic liquids as an environmental friendly alternative. 3,4-Dimethyl-7-hydroxycoumarin (3ab) and 3-isopropyl-4-methyl-5,7-dihydroxycoumarin (3bc) showed interesting activity against Taq DNA polymerase with IC50 values of 115.7 microM and 82.2 microM, respectively. Also, 4-methyl-7-hydroxycoumarin (3aa) and 4-methyl-5,7-dihydroxycoumarin (3ba) exhibited inhibitory activity against MMLV-RT with IC50 values of 23.5 microM and 18.3 microM, respectively. These inhibitors could have importance as antiretroviral chemotherapeutic agents and also for the development of antitumor drugs.

Fluorescent Probes for Sensitive and Selective Detection of pH Changes in Live Cells in Visible and Near-infrared Channels.

PubMed

Fang, Mingxi; Adhikari, Rashmi; Bi, Jianheng; Mazi, Wafa; Dorh, Nethaniah; Wang, Jianbo; Conner, Nathan; Ainsley, Jon; Karabencheva-Christova, Tatyana G; Luo, Fen-Tair; Tiwari, Ashutosh; Liu, Haiying

2017-12-28

We report five fluorescent probes based on coumarin-hybridized fluorescent dyes with spirolactam ring structures (A-E) to detect pH changes in live cell by monitoring visible and near-infrared fluorescence changes. Under physiological or basic conditions, the fluorescent probes A, B, C, D and E preserve their spirolactam ring-closed forms and only display fluorescent peaks in the visible region corresponding to coumarin moieties at 497, 483, 498, 497 and 482 nm, respectively. However, at acidic pH, the rings of the spirolactam forms of the fluorescent probes A, B, C, D and E open up, generating new near-infrared fluorescence peaks at 711, 696, 707, 715, and 697 nm, respectively, through significantly extended π-conjugation to coumarin moieties of the fluorophores. The fluorescent probes B and E can be applied to visualize pH changes by monitoring visible as well as near-infrared fluorescence changes. This helps avoid fluorescence imaging blind spots at neutral or basic pH, which typical pH fluorescent probes encounter. The probes exhibit high sensitivity to pH changes, excellent photostability, low auto-fluorescence background and good cell membrane permeability.

Acquiring High-Performance Deep-Blue OLED Emitters through an Unexpected Blueshift Color-Tuning Effect Induced by Electron-Donating -OMe Substituents.

PubMed

Peng, Song; Zhao, Yihuan; Fu, Caixia; Pu, Xuemei; Zhou, Liang; Huang, Yan; Lu, Zhiyun

2018-06-07

A series of blue-emissive 7-(diphenylamino)-4-phenoxycoumarin derivatives bearing -CF 3 , -OMe, or -N(Me) 2 substituents on the phenoxy subunit were synthesized. Although both the -CF 3 and -N(Me) 2 modifications were found to trigger redshifted fluorescence, the -OMe substitution was demonstrated to exert an unexpected blueshift color-tuning effect toward the deep-blue region. The reason is that the moderate electron-donating -OMe group can endow coumarins with unaltered HOMO but elevated LUMO energy levels. Moreover, the -OMe substitution was found to be beneficial to the thermal stability of these coumarins. Therefore, the trimethoxy-substituted objective compound can act as a high-performance deep-blue organic light-emitting diode (OLED) emitter, and OLED based on it emits deep-blue light with CIE coordinates of (0.148, 0.084), maximum luminance of 7800 cd m -2 , and maximum external quantum efficiency of 5.1 %. These results not only shed light on the molecular design strategy for high-performance deep-blue OLED emitters through color-tuning, but also show the perspective of coumarin derivatives as deep-blue OLED emitters. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Visualization of Fluoride Ions In Vivo Using a Gadolinium(III)-Coumarin Complex-Based Fluorescence/MRI Dual-Modal Probe

PubMed Central

Wang, Yue; Song, Renfeng; Feng, Huan; Guo, Ke; Meng, Qingtao; Chi, Haijun; Zhang, Run; Zhang, Zhiqiang

2016-01-01

A new Gadolinium(III)–coumarin complex, DO3A-Gd-CA, was designed and prepared as a dual-modal probe for simultaneous fluorescence and relaxivity responses to fluoride ions (F−) in aqueous media and mice. DO3A-Gd-CA was designed by using Gd(III) center as an MRI signal output unit and fluoride binding site, and the 4-(diethylamino)-coumarin-3-carboxylic acid (CA) as a fluorescence reporter. Upon the addition of fluoride ions to the solution of DO3A-Gd-CA, the liberation of the coordinated CA ligand led to a 5.7-fold fluorescence enhancement and a 75% increase in the longitudinal relaxivity (r1). The fluorescent detection limit for fluoride ions was determined to be 8 μM based on a 3σ/slope. The desirable features of the proposed DO3A-Gd-CA, such as high sensitivity and specificity, reliability at physiological pH and low cytotoxicity enable its application in visualization of fluoride ion in mice. The successful in vivo imaging indicates that DO3A-Gd-CA could be potentially used in biomedical diagnosis fields. PMID:27999298

Surface functionalization of gold nanoparticles using hetero-bifunctional poly(ethylene glycol) spacer for intracellular tracking and delivery

PubMed Central

Shenoy, Dinesh; Fu, Wei; Li, Jane; Crasto, Curtis; Jones, Graham; DiMarzio, Charles; Sridhar, Srinivas; Amiji, Mansoor

2006-01-01

For the development of surface-functionalized gold nanoparticles as cellular probes and delivery agents, we have synthesized hetero-bifunctional poly(ethylene glycol) (PEG, MW 1500) having a thiol group on one terminus and a reactive functional group on the other for use as a flexible spacer. Coumarin, a model fluorescent dye, was conjugated to one end of the PEG spacer and gold nanoparticles were modified with coumarin-PEG-thiol. Surface attachment of coumarin through the PEG spacer decreased the fluorescence quenching effect of gold nanoparticles. The results of cellular cytotoxicity and fluorescence confocal analyses showed that the PEG spacer-modified nanoparticles were essentially non-toxic and could be efficiently internalized in the cells within 1 hour of incubation. Intracellular particle tracking using a Keck 3-D Fusion Microscope System showed that the functionalized gold nanoparticles were rapidly internalized in the cells and localized in the peri-nuclear region. Using the PEG spacer, the gold nano-platform can be conjugated with a variety of biologically relevant ligands such as fluorescent dyes, antibodies, etc in order to target, probe, and induce a stimulus at the target site. PMID:16467923

Observation of excited state charge transfer with fs/ps-CARS

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

Blom, Alex Jason

2009-01-01

Excited state charge transfer processes are studied using the fs/ps-CARS probe technique. This probe allows for multiplexed detection of Raman active vibrational modes. Systems studied include Michler's Ketone, Coumarin 120, 4-dimethylamino-4'-nitrostilbene, and several others. The vibrational spectrum of the para di-substituted benzophenone Michler's Ketone in the first excited singlet state is studied for the first time. It is found that there are several vibrational modes indicative of structural changes of the excited molecule. A combined experimental and theoretical approach is used to study the simplest 7-amino-4-methylcoumarin, Coumarin 120. Vibrations observed in FTIR and spontaneous Raman spectra are assigned using densitymore » functional calculations and a continuum solvation model is used to predict how observed modes are affected upon inclusion of a solvent. The low frequency modes of the excited state charge transfer species 4-dimethylamino-4{prime}-nitrostilbene are studied in acetonitrile. Results are compared to previous work on this molecule in the fingerprint region. Finally, several partially completed projects and their implications are discussed. These include the two photon absorption of Coumarin 120, nanoconfinement in cyclodextrin cavities and sensitization of titania nanoparticles.« less

Visualization of Fluoride Ions In Vivo Using a Gadolinium(III)-Coumarin Complex-Based Fluorescence/MRI Dual-Modal Probe.

PubMed

Wang, Yue; Song, Renfeng; Feng, Huan; Guo, Ke; Meng, Qingtao; Chi, Haijun; Zhang, Run; Zhang, Zhiqiang

2016-12-16

A new Gadolinium(III)-coumarin complex, DO3A-Gd- CA , was designed and prepared as a dual-modal probe for simultaneous fluorescence and relaxivity responses to fluoride ions (F - ) in aqueous media and mice. DO3A-Gd- CA was designed by using Gd(III) center as an MRI signal output unit and fluoride binding site, and the 4-(diethylamino)-coumarin-3-carboxylic acid ( CA ) as a fluorescence reporter. Upon the addition of fluoride ions to the solution of DO3A-Gd- CA , the liberation of the coordinated CA ligand led to a 5.7-fold fluorescence enhancement and a 75% increase in the longitudinal relaxivity ( r ₁). The fluorescent detection limit for fluoride ions was determined to be 8 μM based on a 3 σ / slope . The desirable features of the proposed DO3A-Gd- CA , such as high sensitivity and specificity, reliability at physiological pH and low cytotoxicity enable its application in visualization of fluoride ion in mice. The successful in vivo imaging indicates that DO3A-Gd- CA could be potentially used in biomedical diagnosis fields.

NorA efflux pump inhibitory activity of coumarins from Mesua ferrea.

PubMed

Roy, Somendu K; Kumari, Neela; Pahwa, Sonika; Agrahari, Udai C; Bhutani, Kamlesh K; Jachak, Sanjay M; Nandanwar, Hemraj

2013-10-01

The purpose of this investigation was to study the modulator and efflux pump inhibitor activity of coumarins isolated from Mesua ferrea against clinical strains as well as NorA-over expressed strain of Staphylococcus aureus 1199B. Seven coumarins were tested for modulator activity using ethidium bromide (EtBr) as a substrate. Compounds 1, 4-7 modulated the MIC of EtBr by ≥ 2 fold against wild type clinical strains of S. aureus 1199 and S. aureus 1199B, whereas compounds 4-7 modulated the MIC of EtBr by ≥ 16 fold against MRSA 831. Compounds 1, 4-7 also reduced the MIC of norfloxacin by ≥ 8 fold against S. aureus 1199B, and 4-6 reduced the MIC of norfloxacin by ≥ 8 fold against MRSA 831 at half of their MICs. Inhibition of EtBr efflux by NorA-overproducing S. aureus 1199B and MRSA 831 confirmed the role of compounds 4-6 as NorA efflux pump inhibitors (EPI). Dose-dependent activity at sub-inhibitory concentration (6.25 μg/mL) suggested that compounds 4 and 5 are promising EPI compared to verapamil against 1199B and MRSA 831 strains. © 2013.

One-pot synthesis, quantum chemical calculations and X-ray diffraction studies of thiazolyl-coumarin hybrid compounds

NASA Astrophysics Data System (ADS)

Saeed, Aamer; Arif, Mubeen; Erben, Mauricio F.; Flörke, Ulrich; Simpson, Jim

2018-06-01

Two closely related hybrid species containing both, thiazolyl and coumarin groups, were synthesized by using two different one-pot procedures from a common precursor. The reaction of α-bromoacetylcoumarin with thioacetamide in methanol furnished 3‑(2‑methylthiazol‑4‑yl)‑2H‑chromen‑2‑one (2), whereas refluxing α‑bromoacetylcoumarin with potassium thiocyanate in ethanol afforded 3‑(2‑ethoxythiazol‑4‑yl)‑2H‑chromen‑2‑one (3). Both derivatives were fully characterized by spectroscopic methods, elemental analysis and X-ray diffraction studies. Intramolecular C4sbnd H⋯N and C5‧sbnd H⋯Odbnd C hydrogen bonds between the heterocycles determine the conformational behavior. The co-planarity of the coumarin and thiazolyl rings favors the occurrence of two remote orbital interactions involving the oxygen and nitrogen lone pairs and the corresponding σ*Csbnd H electron acceptor, as demonstrated by Natural Bond Orbital population analysis. The 2-substitution of the thiazol‑4‑yl group has little effect on the molecular structures but causes significant differences in the crystal packing of the two compounds.

Mechanistic Study of the Validity of Using Hydroxyl Radical Probes To Characterize Electrochemical Advanced Oxidation Processes.

PubMed

Jing, Yin; Chaplin, Brian P

2017-02-21

The detection of hydroxyl radicals (OH • ) is typically accomplished by using reactive probe molecules, but prior studies have not thoroughly investigated the suitability of these probes for use in electrochemical advanced oxidation processes (EAOPs), due to the neglect of alternative reaction mechanisms. In this study, we investigated the suitability of four OH • probes (coumarin, p-chlorobenzoic acid, terephthalic acid, and p-benzoquinone) for use in EAOPs. Experimental results indicated that both coumarin and p-chlorobenzoic acid are oxidized via direct electron transfer reactions, while p-benzoquinone and terephthalic acid are not. Coumarin oxidation to form the OH • adduct product 7-hydroxycoumarin was found at anodic potentials lower than that necessary for OH • formation. Density functional theory (DFT) simulations found a thermodynamically favorable and non-OH • mediated pathway for 7-hydroxycoumarin formation, which is activationless at anodic potentials > 2.10 V/SHE. DFT simulations also provided estimates of E° values for a series of OH • probe compounds, which agreed with voltammetry results. Results from this study indicated that terephthalic acid is the most appropriate OH • probe compound for the characterization of electrochemical and catalytic systems.

Smart coumarin-tagged imprinted polymers for the rapid detection of tamoxifen.

PubMed

Ray, Judith V; Mirata, Fosca; Pérollier, Celine; Arotcarena, Michel; Bayoudh, Sami; Resmini, Marina

2016-03-01

A signalling molecularly imprinted polymer was synthesised for easy detection of tamoxifen and its metabolites. 6-Vinylcoumarin-4-carboxylic acid (VCC) was synthesised from 4-bromophenol to give a fluorescent monomer, designed to switch off upon binding of tamoxifen. Clomiphene, a chlorinated analogue, was used as the template for the imprinting, and its ability to quench the coumarin fluorescence when used in a 1:1 ratio was demonstrated. Tamoxifen and 4-hydroxytamoxifen were also shown to quench coumarin fluorescence. Imprinted and non-imprinted polymers were synthesised using VCC, methacrylic acid as a backbone monomer and ethylene glycol dimethacrylate as cross-linker, and were ground and sieved to particle sizes ranging between 45 and 25 μm. Rebinding experiments demonstrate that the imprinted polymer shows very strong affinity for both clomiphene and tamoxifen, while the non-imprinted polymer shows negligible rebinding. The fluorescence of the imprinted polymer is quenched by clomiphene, tamoxifen and 4-hydroxytamoxifen. The switch off in fluorescence of the imprinted polymer under these conditions could also be detected under a UV lamp with the naked eye, making this matrix suitable for applications when coupled with a sample preparation system.

No oral-cavity-only discrimination of purely olfactory odorants.

PubMed

Stephenson, Dejaimenay; Halpern, Bruce P

2009-02-01

The purely olfactory odorants coumarin, octanoic acid, phenylethyl alcohol, and vanillin had been found to be consistently identified when presented retronasally but could not be identified when presented oral-cavity only (OCO). However, OCO discrimination of these odorants was not tested. Consequently, it remained possible that the oral cavity trigeminal system might provide sufficient information to differentiate these purely olfactory odorants. To evaluate this, 20 participants attempted to discriminate vapor-phase coumarin, octanoic acid, phenylethyl alcohol, and vanillin and, as a control, the trigeminal stimulus peppermint extract, from their glycerin solvent, all presented OCO. None of the purely olfactory odorants could be discriminated OCO, but, as expected, peppermint extract was consistently discriminated. This inability to discriminate clarifies and expands the previous report of lack of OCO identification of purely olfactory odorants. Taken together with prior data, these results suggest that the oral cavity trigeminal system is fully unresponsive to these odorants in vapor phase and that coumarin, octanoic acid, phenylethyl alcohol, and vanillin are indeed purely olfactory stimuli. The OCO discrimination of peppermint extract demonstrated that the absence of discrimination for the purely olfactory odorants was odorant dependent and confirmed that the oral cavity trigeminal system will provide differential response information to some vapor-phase stimuli.

Photostability of low cost dye-sensitized solar cells based on natural and synthetic dyes

NASA Astrophysics Data System (ADS)

Abdou, E. M.; Hafez, H. S.; Bakir, E.; Abdel-Mottaleb, M. S. A.

2013-11-01

This paper deals with the use of some natural pigments as well as synthetic dyes to act as sensitizers in dye-sensitized solar cells (DSSCs). Anthocyanin dye extracted from rosella (Hibiscus sabdariffa L.) flowers, the commercially available textile dye Remazole Red RB-133 (RR) and merocyanin-like dye based on 7-methyl coumarin are tested. The photostability of the three dyes is investigated under UV-Vis light exposure. The results show a relatively high stability of the three dyes. Moreover, the photostability of the solid dyes is studied over the TiO2 film electrodes. A very low decolorization rates are recorded as; rate constants k = 1.6, 2.1 and 1.9 × 10-3 min-1 for anthocyanin, RR and coumarin dyes, respectively. The stability results favor selecting anthocyanin as a promising sensitizer candidate in DSSCs based on natural products. Dyes-sensitized solar cells are fabricated and their conversion efficiency (η) is 0.27%, 0.14% and 0.001% for the anthocyanin, RR and coumarin dyes, respectively. Moreover, stability tests of the sealed cells based on anthocyanin and RR dyes are done under continuous light exposure of 100 mW cm-2, reveals highly stable DSSCs.

Novel coumarin derivatives bearing N-benzyl pyridinium moiety: potent and dual binding site acetylcholinesterase inhibitors.

PubMed

Alipour, Masoumeh; Khoobi, Mehdi; Foroumadi, Alireza; Nadri, Hamid; Moradi, Alireza; Sakhteman, Amirhossein; Ghandi, Mehdi; Shafiee, Abbas

2012-12-15

A novel series of coumarin derivatives linked to benzyl pyridinium group were synthesized and biologically evaluated as inhibitors of both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The enzyme inhibitory activity of synthesized compounds was measured using colorimetric Ellman's method. It was revealed that compounds 3e, 3h, 3l, 3r and 3s have shown higher activity compared with donepezil hydrochloride as standard drug. Most of the compounds in these series had nanomolar range IC(50) in which compound 3r (IC(50) = 0.11 nM) was the most active compound against acetylcholinesterase enzyme. Copyright © 2012 Elsevier Ltd. All rights reserved.

Synthesis of some new 3-coumaranone and coumarin derivatives as dual inhibitors of acetyl- and butyrylcholinesterase.

PubMed

Alipour, Masoumeh; Khoobi, Mehdi; Nadri, Hamid; Sakhteman, Amirhossein; Moradi, Alireza; Ghandi, Mehdi; Foroumadi, Alireza; Shafiee, Abbas

2013-08-01

A novel series of coumarin and 3-coumaranone derivatives encompassing the phenacyl pyridinium moiety were synthesized and evaluated for their acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activity using Ellman's method. All compounds presented inhibitory activity against both AChE and BuChE in the micromolar range. The molecular docking simulations revealed that all compounds were dual binding site inhibitors of AChE. A kinetic study was performed and the mechanism of enzyme inhibition was proved to be of mixed type. All compounds were tested for their antioxidant activity and no significant activity was observed. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

An approach of ionic liquids/lithium salts based microwave irradiation pretreatment followed by ultrasound-microwave synergistic extraction for two coumarins preparation from Cortex fraxini.

PubMed

Liu, Zaizhi; Gu, Huiyan; Yang, Lei

2015-10-23

Ionic liquids/lithium salts solvent system was successfully introduced into the separation technique for the preparation of two coumarins (aesculin and aesculetin) from Cortex fraxini. Ionic liquids/lithium salts based microwave irradiation pretreatment followed by ultrasound-microwave synergy extraction (ILSMP-UMSE) procedure was developed and optimized for the sufficient extraction of these two analytes. Several variables which can potentially influence the extraction yields, including pretreatment time and temperature, [C4mim]Br concentration, LiAc content, ultrasound-microwave synergy extraction (UMSE) time, liquid-solid ratio, and UMSE power were optimized by Plackett-Burman design. Among seven variables, UMSE time, liquid-solid ratio, and UMSE power were the statistically significant variables and these three factors were further optimized by Box-Behnken design to predict optimal extraction conditions and find out operability ranges with maximum extraction yields. Under optimum operating conditions, ILSMP-UMSE showed higher extraction yields of two target compounds than those obtained by reference extraction solvents. Method validation studies also evidenced that ILSMP-UMSE is credible for the preparation of two coumarins from Cortex fraxini. This study is indicative of the proposed procedure that has huge application prospects for the preparation of natural products from plant materials. Copyright © 2015 Elsevier B.V. All rights reserved.

Utility of Von Pechman synthesis of coumarin reaction for development of spectrofluorimetric method for quantitation of salmeterol xinafoate in pharmaceutical preparations and human plasma.

PubMed

Awad, Mohamed; Hammad, Mohamed A; Abdel-Megied, Ahmed M; Omar, Mahmoud A

2018-04-30

Simple, precise and selective spectrofluorimetric technique was evolved for quantitation of selective β 2 agonist drug namely salmeterol xinafoate (SAL). Utilizing its phenolic nature, a method was described based on the reaction of the studied drug with ethyl acetoacetate (EAA) to yield extremely fluorescent coumarin product which can be detected at 480 nm (λ ex  = 420 nm). The procedure obeys Beer's law with a correlation coefficient of r = 0.9999 in the concentration range between 500 and 5000 ng ml -1 with and 177 ng ml -1 for limit of detection (LOD) and limit of quantification (LOQ), respectively. Diverse reaction variables influencing the firmness and formation of the coumarin product were accurately examined and modified to ensure greatest sensitivity of the procedure. The proposed technique was performed and examined according to the US Food and Drug Administration (FDA) guidelines for bio-analytical methods and was efficiently applied for quantitation of SAL in both pharmaceutical preparations (% recovery = 100.06 ± 1.07) and spiked human plasma (% recovery = 96.64-97.14 ± 1.01-1.52). Copyright © 2018 John Wiley & Sons, Ltd.

Amphiphilic complexes of Ho(iii), Dy(iii), Tb(iii) and Eu(iii) for optical and high field magnetic resonance imaging.

PubMed

Harris, Michael; Henoumont, Céline; Peeters, Wannes; Toyouchi, Shuichi; Vander Elst, Luce; Parac-Vogt, Tatjana N

2018-05-29

Lanthanides, holmium(iii), dysprosium(iii), and terbium(iii), were coordinated to an amphiphilic DOTA bis-coumarin derivative and then further assembled with an amphiphilic europium(iii) DTPA bis-coumarin derivative into mono-disperse micelles. The self-assembled micelles were characterized and assessed for their potential as bimodal contrast agents for high field magnetic resonance and optical imaging applications. All micelles showed a high transverse relaxation (r2) of 46, 34, and 30 s-1 mM-1 at 500 MHz and 37 °C for Dy(iii), Ho(iii) and Tb(iii), respectively, which is a result of the high magnetic moment of these lanthanides and the long rotational correlation time of the micelles. The quantum yield in aqueous solution ranged from 1.8% for Tb/Eu to 1.4% for Dy/Eu and 1.0% for the Ho/Eu micelles. Multi-photon excited emission spectroscopy has shown that due to the two-photon absorption of the coumarin chromophore the characteristic Eu(iii) emission could be observed upon excitation at 800 nm, demonstrating the usefulness of the system for in vivo fluorescence imaging applications. To the best of our knowledge, this is the first example reporting the potential of a holmium(iii) chelate as a negative MRI contrast agent.

In vivo modulation of the behavioral effects of nicotine by the coumarins xanthotoxin, bergapten, and umbelliferone.

PubMed

Budzynska, Barbara; Skalicka-Wozniak, Krystyna; Kruk-Slomka, Marta; Wydrzynska-Kuzma, Malgorzata; Biala, Grazyna

2016-06-01

Nicotine, a dominant alkaloid found in tobacco, is responsible for physical dependence, as well as addiction to cigarette smoking; consequently, smoking cessation is a very difficult process. Hepatic cytochrome P-450 2A6 (CYP2A6) is involved in the 70-80 % of the initial metabolism of nicotine and its co-metabolites. As this metabolism is slowed by inhibitors of CYP2A6, this kind of enzymatic inhibition has been proposed as a novel target for smoking cessation. Nicotine administered alone improved memory acquisition and consolidation as well as exerted antidepressive activity in animal models. These effects persist for 24 h. However, they are completely extinguished 48 h after administration. To investigate if the coumarins prolong the behavioral effects of nicotine, the forced swimming test (FST)-animal models of depression, and passive avoidance (PA) test-memory and learning paradigm were used. This study revealed that three CYP2A6 inhibitors: two furanocoumarins, xanthotoxin (15 mg/kg) and bergapten (25 mg/kg), and the simple coumarin umbelliferone (25 mg/kg), prolonged the antidepressive and procognitive effects of nicotine. These natural products may offer a new approach to the treatment of nicotinism as antidepressant and memory improvement actions are one of the main factors of nicotine dependence.

Coumarins with α-glucosidase and α-amylase inhibitory activities from the flower of Edgeworthia gardneri.

PubMed

Zhao, Deng-Gao; Zhou, Ai-Yu; Du, Zhiyun; Zhang, Yu; Zhang, Kun; Ma, Yan-Yan

2015-12-01

The flower of Edgeworthia gardneri is consumed in beverages in Tibet and has potential health benefits for diabetes. As a part of our continuous studies on dietary supplements for diabetes, two monomers, five dimers and one trimer of coumarins were isolated from the flowers of E. gardneri. One dimer was a new compound (1) and its structure was determined by spectroscopic methods, including multiple NMR techniques and mass spectrometry. The inhibitory activities of all coumarins against α-amylase and α-glucosidase were evaluated. Compound 4 displayed potent inhibitory effect on both α-amylase and α-glucosidase, with an IC50 of 90 and 86μg/mL, respectively. The IC50 of compound 3 against α-glucosidase was 18.7μg/mL, and its inhibition mode was noncompetitive. Based on the fluorescence analysis, the binding constant and the number of binding sites of compound 3 were calculated as 2.05×10(5) and 1.24, respectively. Furthermore, the interaction between compound 3 and α-glucosidase was a spontaneous process that was driven mainly by hydrophobic force. This study could facilitate the utilization of E gardneri as functional food ingredient. Copyright © 2015 Elsevier B.V. All rights reserved.

Antagonists for the orphan G-protein-coupled receptor GPR55 based on a coumarin scaffold.

PubMed

Rempel, Viktor; Volz, Nicole; Gläser, Franziska; Nieger, Martin; Bräse, Stefan; Müller, Christa E

2013-06-13

The orphan G-protein-coupled receptor GPR55, which is activated by 1-lysophosphatidylinositol and interacts with cannabinoid (CB) receptor ligands, has been proposed as a new potential drug target for the treatment of diabetes, Parkinson's disease, neuropathic pain, and cancer. We applied β-arrestin assays to identify 3-substituted coumarins as a novel class of antagonists and performed an extensive structure-activity relationship study for GPR55. Selectivity versus the related receptors CB1, CB2, and GPR18 was assessed. Among the 7-unsubstituted coumarins selective, competitive GPR55 antagonists were identified, such as 3-(2-hydroxybenzyl)-5-isopropyl-8-methyl-2H-chromen-2-one (12, PSB-SB-489, IC50 = 1.77 μM, pA2 = 0.547 μM). Derivatives with long alkyl chains in position 7 were potent, possibly allosteric GPR55 antagonists which showed ancillary CB receptor affinity. 7-(1,1-Dimethyloctyl)-5-hydroxy-3-(2-hydroxybenzyl)-2H-chromen-2-one (69, PSB-SB-487, IC50 = 0.113 μM, KB = 0.561 μM) and 7-(1,1-dimethylheptyl)-5-hydroxy-3-(2-hydroxybenzyl)-2H-chromen-2-one (67, PSB-SB-1203, IC50 = 0.261 μM) were the most potent GPR55 antagonists of the present series.

A Nanosystem Capable of Releasing a Photosensitizer Bioprecursor under Two‐Photon Irradiation for Photodynamic Therapy

PubMed Central

Wu, Hao; Zeng, Fang; Zhang, Hang; Xu, Jiangsheng

2015-01-01

The applications of photodynamic therapy (PDT) are usually limited by photosensitizers' side effects and singlet oxygen's short half‐life. Herein, a mitochondria‐targeted nanosystem is demonstrated to enhance the PDT efficacy by releasing a bio‐precursor of photosensitizer under two‐photon irradiation. A phototriggerable coumarin derivative is first synthesized by linking 5‐aminolevulinic acid (5‐ALA, the bio‐precursor) to coumarin; and the nanosystem (CD‐ALA‐TPP) is then fabricated by covalently incorporating this coumarin derivative and a mitochondria‐targeting compound triphenylphosphonium (TPP) onto carbon dots (CDs). Upon cellular internalization, the nanosystem preferentially accumulates in mitochondria; and under one‐ or two‐photon irradiation, it releases 5‐ALA molecules that are then metabolized into protoporphyrin IX in mitochondria through a series of biosynthesis processes. The subsequent red light irradiation induces this endogenously synthesized photosensitizer to generate singlet oxygen, thereby causing oxidant damage to mitochondria and then the apoptosis of the cells. Analysis via 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyltetrazolium bromide (MTT) assays indicate that the novel PDT system exhibits enhanced cytotoxicity toward cancer cells. This study may offer a new strategy for designing PDT systems with high efficacy and low side effects. PMID:27774388

Inhibitory effects of coumarins from the stem barks of Fraxinus rhynchophylla on adipocyte differentiation in 3T3-L1 cells.

PubMed

Shin, Eunjin; Choi, Kyeong-Mi; Yoo, Hwan-Soo; Lee, Chong-Kil; Hwang, Bang Yeon; Lee, Mi Kyeong

2010-01-01

In the course of screening anti-adipogenic activity of natural products employing the preadipocyte cell line, 3T3-L1 as an in vitro assay system, the EtOAc fraction of the stem barks of Fraxinus rhynchophylla DENCE (Oleaceae) showed significant inhibitory activity on adipocyte differentiation as assessed by measuring fat accumulation using Oil Red O staining. Activity-guided fractionation led to the isolation of six coumarins such as esculetin (1), scopoletin (2), fraxetin (3), fraxidin (4) esculin (5) and fraxin (6). Among the six coumarins isolated, esculetin (1) showed the most potent inhibitory activity on adipocyte differentiation, followed by fraxetin (3). Further studies with interval treatment demonstrated that esculetin (1) exerted inhibitory activity on adipocyte differentiation when treated within 2 d (days 0-2) after differentiation induction. We further investigated the effect of esculetin (1) on peroxisome proliferator activated receptor gamma (PPARgamma), one of the early adipogenic transcription factors. Esculetin (1) significantly blocked the induction of PPARgamma protein expression and inhibited adipocyte differentiation induced by troglitazone, a PPARgamma agonist. Taken together, these results suggest that esculetin (1), an active compound from F. rhynchophylla, inhibited early stage of adipogenic differentiation, in part, via inhibition of PPARgamma-dependent pathway.

A new ratiometric and colorimetric chemosensor for cyanide anion based on coumarin-hemicyanine hybrid.

PubMed

Yang, Zhenghao; Liu, Zhipeng; Chen, Yuncong; Wang, Xiaoqing; He, Weijiang; Lu, Yi

2012-07-14

A hybrid coumarin-hemicyanine dye, Cou-BT, was developed as a new ratiometric and colorimetric sensor for cyanide with a sensing mechanism via nucleophilic addition of cyanide anion to the benzothiolium group. Cou-BT shows high sensitivity and selectivity for cyanide detection over other common anion species in aqueous acetonitrile solution. The calculated pseudo-first-order rate constant for cyanide anion addition was (2.13 ± 0.08) × 10(-2) s(-1) at 298 K, and the detection limit was estimated to be 0.64 μM. The DFT and TDDFT calculation results suggest that the ratiometric and colorimetric sensing behavior of Cou-BT upon its reaction with cyanide was due to the interrupted π-conjugation and blocked ICT progress.

Highly selective on-off fluorescence recognition of Fe3+ based on a coumarin derivative and its application in live-cell imaging

NASA Astrophysics Data System (ADS)

Warrier, Sona; Kharkar, Prashant S.

2018-01-01

A novel coumarin chemosensor, 7-hydroxy-2-oxo-N-(pyridin-2-ylmethyl)chromene-3-carboxamide (Probe 1), demonstrated significant selectivity towards Fe3+ ions. Probe 1 exhibited high fluorescence emission profile at 447 nm, excellent selectivity towards Fe3+ over other biologically important metal ions (Al3+, Ba2+, Co2+, Cu2+, Zn2+, Cd2+, Hg2+, Pb2+ and Sn2+). Interestingly, there was 30-fold decrease in fluorescence intensity upon Fe3+ binding. The limit of detection of Fe3+ was found to be 0.76 μM ( 40 ppb). Probe 1 also exhibited high potential as an intracellular chemosensor for Fe3+.

Antiinflammatory effect of Japanese horse chestnut (Aesculus turbinata) seeds.

PubMed

Sato, Itaru; Kofujita, Hisayoshi; Suzuki, Tadahiko; Kobayashi, Haruo; Tsuda, Shuji

2006-05-01

The antiinflammatory effects of Japanese horse chestnut (Aesculus turbinata) seeds were examined in vivo and in vitro. The extract of this seed (HCSE) inhibited croton oil-induced swelling of the mouse concha. HCSE inhibited cyclooxygenase (COX) -1 and -2 activities, but had no effect on 15-lipoxygenase and phospholipase A2 activities. Inhibition of COX-2 occurred at a lower concentration of HCSE than for COX-1. Japanese horse chestnut seeds contain coumarins and saponins, but these chemicals did not inhibit COX activities. These results suggest that the antiinflammatory effect of Japanese horse chestnut seeds is caused, at least partly, by the inhibition of COX. The inhibitor of COX in this seed may be a chemical(s) other than coumarins and saponins.

A novel fluoride ion colorimetric chemosensor based on coumarin.

PubMed

Zhuang, Xiaoqing; Liu, Weimin; Wu, Jiasheng; Zhang, Hongyan; Wang, Pengfei

2011-09-01

A novel visible colorimetric sensor (L1) with high selectivity for fluoride ion based on coumarin has been synthesized by a simple modification of our earlier report. The chemosensor L1 shows an obvious color change from yellow to blue upon addition of fluoride ion with a large red shift of 145 nm in acetonitrile, and without interference of other anions such as Cl-, Br-, I-, NO3-, H2PO4-, HSO4-, and AcO-. The investigation of 1H NMR spectrum titration indicates the proposed mechanism is that F- first establishes a hydrogen bonding interaction with L1, and then the formation of [F-H-F]- induces deprotonation. Copyright © 2011 Elsevier B.V. All rights reserved.

Structural, spectral and NBO analysis of 3-(1-(3-hydroxypropylamino)ethylidene)chroman-2,4-dione

NASA Astrophysics Data System (ADS)

Avdović, Edina H.; Milenković, Dejan; Dimitrić-Marković, Jasmina M.; Vuković, Nenad; Trifunović, Srećko R.; Marković, Zoran

2017-11-01

The structure of the newly synthesized coumarin derivative, 3-(1-(3-hydroxypropylamino)-ethylidene)-chroman-2,4-dione, was investigated experimentally and theoretically. FTIR, 1H and 13C NMR spectroscopic methods along with the density functional theory calculations, with B3LYP functional (and with empirical dispersion corrections D3BJ) in combination with the 6-311+G(d,p) basis set, are performed in order to characterize the molecular structure and spectroscopic behavior of the investigated coumarin derivative. Molecular docking analysis was carried out in order to identify the potency of inhibition of the title molecule against human C-reactive protein. The inhibition activity was obtained for ten conformations of ligand inside protein.

Coumarin-Based Oxime Esters: Photobleachable and Versatile Unimolecular Initiators for Acrylate and Thiol-Based Click Photopolymerization under Visible Light-Emitting Diode Light Irradiation.

PubMed

Li, Zhiquan; Zou, Xiucheng; Zhu, Guigang; Liu, Xiaoya; Liu, Ren

2018-05-09

Developing efficient unimolecular visible light-emitting diode (LED) light photoinitiators (PIs) with photobleaching capability, which are essential for various biomedical applications and photopolymerization of thick materials, remains a great challenge. Herein, we demonstrate the synthesis of a series of novel PIs, containing coumarin moieties as chromophores and oxime ester groups as initiation functionalities and explore their structure-activity relationship. The investigated oxime esters can effectively induce acrylates and thiol-based click photopolymerization under 450 nm visible LED light irradiation. The initiator O-3 exhibited excellent photobleaching capability and enabled photopolymerization of thick materials (∼4.8 mm). The efficient unimolecular photobleachable initiators show great potential in dental materials and 3D printings.

[Pharmacokinetics of α-asarone after intranasal and intravenous administration with PLA-α-asarone nanoparticles].

PubMed

Lu, Jin; Guo, Li-Wei; Fu, Ting-Ming; Zhu, Guo-Long; Dai, Zhen-Nan; Zhan, Guan-Jun; Chen, Li-Li

2017-06-01

PLA-α-asarone nanoparticles were prepared by using organic solvent evaporation method, and their in vivo distribution and brain targeting after intranasal administration were studied as compared with intravenous administration. The results showed that brain targeting coefficient of PLA-α-asarone nanoparticles after intranasal and intravenous administration was 1.65 and 1.16 respectively. The absolute bioavailability, brain-targeting efficiency and the percentage of nasal-brain delivery of PLA-α-asarone nanoparticles were 74.2%, 142.24 and 29.83%, respectively after intranasal administration. The results of fluorescence labeling showed that the fluorescent intensity of coumarin-6 in the brain tissue was the highest after intranasal administration of PLA-α-asarone fluorescent nanoparticles, achieving the purpose of brain-targeted drug delivery. The fluorescent intensity of coumarin-6 in liver tissue after intravenous administration of PLA-α-asarone nanoparticles was much higher than that after intranasal administration, indicating that intranasal administration of PLA-α-asarone nanoparticles could decrease drug-induced hepatotoxicity. In addition, the fluorescent intensity of coumarin-6 in lung tissue was weaker after intranasal administration, which solved the shortcomings of intranasal administration of α-asarone dry powder prepared by airflow pulverization method. In vivo studies indicated that PLA-α-asarone nanoparticles after intranasal administration had a stronger brain targeting as compared with intravenous administration. Copyright© by the Chinese Pharmaceutical Association.

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.

Selective and sensitive fluorescent sensor for Pd2+ using coumarin 460 for real-time and biological applications.

PubMed

Ashwin, Bosco Christin Maria Arputham; Sivaraman, Gandhi; Stalin, Thambusamy; Yuvakkumar, Rathinam; Muthu Mareeswaran, Paulpandian

2018-06-01

The efficient fluorescent property of coumarin 460 (C460) is utilized to sense the Pd 2+ selectively and sensitively. Fabrication of a sensor strip using commercial adhesive tape is achieved and the detection of Pd 2+ is attempted using a handy UV torch. The naked eye detection in solution state using UV chamber is also attempted. The calculated high binding constant values support the strong stable complex formation of Pd 2+ with C460. The detection limit up to 2.5 × 10 -7  M is achieved using fluorescence spectrometer, which is considerably low from the WHO's recommendation. The response of coumarin 460 with various cations also studied. The quenching is further studied by the lifetime measurements. The binding mechanism is clearly explained by the 1 H NMR titration. The sensing mechanism is established as ICT. C460 strip's Pd 2+ quenching detection is further confirmed by solid-state PL study. The in-vitro response of Pd 2+ in a living cell is also studied using fluorescent imaging studies by means of HeLa cell lines and this probe is very compatible with biological environments. It could be applicable to sense trace amounts of a Pd 2+ ion from various industries. Compared with previous reports, this one is very cheap, sensitive, selective and suitable for biological systems. Copyright © 2018 Elsevier B.V. All rights reserved.

Laser lithotripsy of gallstones: alexandrite and rhodamine-6G versus coumarin dye laser: fragmentation and fiber burn-off in vitro

NASA Astrophysics Data System (ADS)

Hochberger, Juergen; Bredt, Marion; Mueller, Gudrun; Hahn, Eckhart G.; Ell, Christian

1993-05-01

In the following study three different pulsed laser lithotripsy systems were compared for the fine fragmentation of identical sets of natural and synthetic gallstones `in vitro.' Using a pulsed coumarin dye laser (504 nm), a pulsed rhodamine 6G dye laser (595 nm), and a pulsed Alexandrite laser (755 nm) a total of 184 concrements of known chemical composition, size, and weight were disintegrated to a fragment size of

21 CFR 864.7750 - Prothrombin time test.

Code of Federal Regulations, 2010 CFR

2010-04-01

... the detection of possible clotting factor deficiencies in the extrinsic coagulation pathway, which involves the reaction between coagulation factors III and VII, and to monitor patients receiving coumarin...

By inhibiting snail signaling and miR-23a-3p, osthole suppresses the EMT-mediated metastatic ability in prostate cancer

PubMed Central

Wen, Yu-Ching; Lee, Wei-Jiunn; Tan, Peng; Yang, Shun-Fa; Hsiao, Michael; Lee, Liang-Ming; Chien, Ming-Hsien

2015-01-01

Here we showed that Osthole, 7-methoxy-8-(3-methyl-2-butenyl) coumarin, a bioactive coumarin derivative extracted from medicinal plants, inhibited migration, invasion, epithelial to mesenchymal transition (EMT) in androgen-independent prostate cancer (AIPC) cells in vitro and metastasis of AIPC in vivo. In patients, high Snail levels were correlated with a higher histological Gleason sum and poor survival rates. Osthole inhibited the TGF-β/Akt/MAPK pathways, reduced Snail-DNA-binding activity and induced E-cadherin. We found that osthole decreased miR-23a-3p. Ectopic miR-23a-3p suppressed E-cadherin 3′ untranslated region reporter activity and E-cadherin expression, and relieved the motility suppression caused by osthole treatment. PMID:26110567

By inhibiting snail signaling and miR-23a-3p, osthole suppresses the EMT-mediated metastatic ability in prostate cancer.

PubMed

Wen, Yu-Ching; Lee, Wei-Jiunn; Tan, Peng; Yang, Shun-Fa; Hsiao, Michael; Lee, Liang-Ming; Chien, Ming-Hsien

2015-08-28

Here we showed that Osthole, 7-methoxy-8-(3-methyl-2-butenyl) coumarin, a bioactive coumarin derivative extracted from medicinal plants, inhibited migration, invasion, epithelial to mesenchymal transition (EMT) in androgen-independent prostate cancer (AIPC) cells in vitro and metastasis of AIPC in vivo. In patients, high Snail levels were correlated with a higher histological Gleason sum and poor survival rates. Osthole inhibited the TGF-β/Akt/MAPK pathways, reduced Snail-DNA-binding activity and induced E-cadherin. We found that osthole decreased miR-23a-3p. Ectopic miR-23a-3p suppressed E-cadherin 3' untranslated region reporter activity and E-cadherin expression, and relieved the motility suppression caused by osthole treatment.

Biophysical influence of coumarin 35 on bovine serum albumin: Spectroscopic study

NASA Astrophysics Data System (ADS)

Bayraktutan, Tuğba; Onganer, Yavuz

2017-01-01

The binding mechanism and protein-fluorescence probe interactions between bovine serum albumin (BSA) and coumarin 35 (C35) was investigated by using UV-Vis absorption and fluorescence spectroscopies since they remain major research topics in biophysics. The spectroscopic data indicated that a fluorescence quenching process for BSA-C35 system was occurred. The fluorescence quenching processes were analyzed using Stern-Volmer method. In this regard, Stern-Volmer quenching constants (KSV) and binding constants were calculated at different temperatures. The distance r between BSA (donor) and C35 (acceptor) was determined by exploiting fluorescence resonance energy transfer (FRET) method. Synchronous fluorescence spectra were also studied to observe information about conformational changes. Moreover, thermodynamics parameters were calculated for better understanding of interactions and conformational changes of the system.

Highly selective on-off fluorescence recognition of Fe3+ based on a coumarin derivative and its application in live-cell imaging.

PubMed

Warrier, Sona; Kharkar, Prashant S

2018-01-05

A novel coumarin chemosensor, 7-hydroxy-2-oxo-N-(pyridin-2-ylmethyl)chromene-3-carboxamide (Probe 1), demonstrated significant selectivity towards Fe 3+ ions. Probe 1 exhibited high fluorescence emission profile at 447nm, excellent selectivity towards Fe 3+ over other biologically important metal ions (Al 3+ , Ba 2+ , Co 2+ , Cu 2+ , Zn 2+ , Cd 2+ , Hg 2+ , Pb 2+ and Sn 2+ ). Interestingly, there was ~30-fold decrease in fluorescence intensity upon Fe 3+ binding. The limit of detection of Fe 3+ was found to be 0.76μM (~40ppb). Probe 1 also exhibited high potential as an intracellular chemosensor for Fe 3+ . Copyright © 2017 Elsevier B.V. All rights reserved.

Analysis of fragrance compounds in blood samples of mice by gas chromatography, mass spectrometry, GC/FTIR and GC/AES after inhalation of sandalwood oil.

PubMed

Jirovetz, L; Buchbauer, G; Jäger, W; Woidich, A; Nikiforov, A

1992-01-01

After inhalation experiments with sandalwood oil and the pure fragrance compounds coumarin and alpha-terpineol, substances were detected and measured in the blood samples of test animals (mice) using gas chromatography/mass spectrometry (GC/MS) (MID) in connection with GC/FTIR (SWC), GC/AES (carbon and oxygen trace) and flame ionization detection/gas chromatography. Using tiglinic acid benzyl ester as the internal standard the following concentrations in serum could be found: alpha-santalol 6.1 ng/mL, beta-santalol 5.3 ng/mL and alpha-santalene 0.5 ng/mL. In separate inhalation experiments with coumarin and with alpha-terpineol the corresponding concentrations were 7.7 ng/mL and 6.9 ng/mL, respectively.

Convergent Synthesis of Two Fluorescent Ebselen-Coumarin Heterodimers.

PubMed

Küppers, Jim; Schulz-Fincke, Anna Christina; Palus, Jerzy; Giurg, Mirosław; Skarżewski, Jacek; Gütschow, Michael

2016-07-08

The organo-seleniumdrug ebselen exhibits a wide range of pharmacological effects that are predominantly due to its interference with redox systems catalyzed by seleno enzymes, e.g., glutathione peroxidase and thioredoxin reductase. Moreover, ebselen can covalently interact with thiol groups of several enzymes. According to its pleiotropic mode of action, ebselen has been investigated in clinical trials for the prevention and treatment of different ailments. Fluorescence-labeled probes containing ebselen are expected to be suitable for further biological and medicinal studies. We therefore designed and synthesized two coumarin-tagged activity-based probes bearing the ebselen warhead. The heterodimers differ by the nature of the spacer structure, for which-in the second compound-a PEG/two-amide spacer was introduced. The interaction of this probe and of ebselen with two cysteine proteases was investigated.

Microwave-assisted extraction of coumarin and related compounds from Melilotus officinalis (L.) Pallas as an alternative to Soxhlet and ultrasound-assisted extraction.

PubMed

Martino, Emanuela; Ramaiola, Ilaria; Urbano, Mariangela; Bracco, Francesco; Collina, Simona

2006-09-01

Soxhlet extraction, ultrasound-assisted extraction (USAE) and microwaves-assisted extraction (MAE) in closed system have been investigated to determine the content of coumarin, o-coumaric and melilotic acids in flowering tops of Melilotus officinalis. The extracts were analyzed with an appropriate HPLC procedure. The reproducibility of extraction and of chromatographic analysis was proved. Taking into account the extraction yield, the cost and the time, we studied the effects of extraction variables on the yield of the above-mentioned compounds. Better results were obtained with MAE (50% v/v aqueous ethanol, two heating cycles of 5 min, 50 degrees C). On the basis of the ratio extraction yield/extraction time, we therefore propose MAE as the most efficient method.

Study of chemical reactivity in relation to experimental parameters of efficiency in coumarin derivatives for dye sensitized solar cells using DFT.

PubMed

Soto-Rojo, Rody; Baldenebro-López, Jesús; Glossman-Mitnik, Daniel

2015-06-07

A group of dyes derived from coumarin was studied, which consisted of nine molecules using a very similar manufacturing process of dye sensitized solar cells (DSSCs). Optimized geometries, energy levels of the highest occupied molecular orbital and the lowest unoccupied molecular orbital, and ultraviolet-visible spectra were obtained using theoretical calculations, and they were also compared with experimental conversion efficiencies of the DSSC. The representation of an excited state in terms of natural transition orbitals (NTOs) was studied. Chemical reactivity parameters were calculated and correlated with the experimental data linked to the efficiency of the DSSC. A new proposal was obtained to design new molecular systems and to predict their potential use as a dye in DSSCs.

Induction by carrot allelochemicals of insecticide-metabolising enzymes in the southern armyworm (Spodoptera eridania).

PubMed

Brattsten, L B; Evans, C K; Bonetti, S; Zalkow, L H

1984-01-01

Carrot foliage monoterpenes induce cytochrome P-450 up to 2.9-fold, NADPH cytochrome c (P-450) reductase up to 1.6-fold, NADPH-oxidation up to 3.8-fold, aldrin epoxidation up to 1.5-fold in southern armyworm larval midgut tissues when incorporated in their diet at 0.2% for 3 days. Stigmasterol and ergosterol did not substantially induce microsomal oxidase activities and significantly inhibited GSH S-aryltransferase activity and sulfotransferase activity. Coumarin did not substantially affect microsomal oxidase and sulfotransferase activity but is the most potent inducer of GSH S-aryltransferase activity, increasing this activity 7-fold. None of the chemicals is acutely toxic to the sixth instar larvae or affect the larval weight gain except coumarin which significantly depressed the maximal body weight attained.

Copper-redox cycling by coumarin-di(2-picolyl)amine hybrid molecule leads to ROS-mediated DNA damage and apoptosis: A mechanism for cancer chemoprevention.

PubMed

Khan, Saman; Zafar, Atif; Naseem, Imrana

2018-06-25

Coumarin is an important bioactive pharmacophore. It is found in plants as a secondary metabolite and exhibits diverse pharmacological properties including anticancer effects against different malignancies. Therapeutic efficacy of coumarin derivatives depends on the pattern of substitution and conjugation with different moieties. Cancer cells contain elevated copper as compared to normal cells that plays a role in angiogenesis. Thus, targeting copper in malignant cells via copper chelators can serve as an attractive targeted anticancer strategy. Our previous efforts led to the synthesis of di(2-picolyl)amine-3(bromoacetyl)coumarin hybrid molecule (ligand-L) endowed with DNA/Cu(II) binding properties, and ROS generation ability in the presence of copper ions. In the present study, we aimed to validate copper-dependent cytotoxic action of ligand-L against malignant cells. For this, we used a cellular model system of copper (Cu) overloaded lymphocytes (CuOLs) to simulate malignancy-like condition. In CuOLs, lipid peroxidation/protein carbonylation, ROS generation, DNA fragmentation and apoptosis were investigated in the presence of ligand-L. Results showed that ligand-L-Cu(II) interaction leads to ROS generation, lipid peroxidation/protein carbonylation (oxidative stress parameters), DNA damage, up-regulation of p53 and mitochondrial-mediated apoptosis in treated lymphocytes. Further, pre-incubation with neocuproine (membrane permeable copper chelator) and ROS scavengers attenuated the DNA damage and apoptosis. These results suggest that cellular copper acts as molecular target for ligand-L to propagate redox cycling and generation of ROS via Fenton-like reaction leading to DNA damage and apoptosis. Further, we showed that ligand-L targets elevated copper in breast cancer MCF-7 and colon cancer HCT116 cells leading to a pro-oxidant inhibition of proliferation of cancer cells. In conclusion, we propose copper-dependent ROS-mediated mechanism for the cytotoxic action of ligand-L in malignant cells. Thus, targeting elevated copper represents an effective therapeutic strategy for selective cytotoxicity against malignant cells. Copyright © 2018 Elsevier B.V. All rights reserved.

In vitro Drug Metabolism Investigation of 7-Ethoxycoumarin in Human, Monkey, Dog and Rat Hepatocytes by High Resolution LC-MS/MS.

PubMed

Feng, Wan-Yong; Wen, Jenny; Stauber, Kathe

2018-04-18

Recently, it has been an increasing concern on the bioactivation and adverse reactions associated with consumption of herbal and nature products such as coumarin family. 7-ethoxycoumarin is one of coumarin family compounds, but little information is available regarding its potential reactive metabolites. In this study, we investigated its metabolism in cryopreserved male/female mixed human, male Cynomolgus monkey, male Beagle dog and male Sprague Dawley rat hepatocytes. Following the incubation of 7-ethoxylcoumarin in the hepatocytes for 2 hr, 28 metabolites were detected and identified using high resolution LC-Q-Exactive system in the positive ion and negative ion modes. O-deethylation, glucuronidation, sulfation, oxygenation, oxidative ring-opening, hydrogenation, glutathionation, dehydrogenation, cysteination, glucosidation, methylation, and hydrolysis were observed. At least sixteen metabolites were newly identified. M1 (O-deethylation, mono-oxygenation and glucuronidation), M3 (O-deethylation and glucuronidation), M5 (hydrolysis and mono-oxygenation), M14 (Odeethylation), M16 (hydrolysis), M22 (oxidative ring-opening and oxygenation) and M27 (mono-oxygenation) appeared to be major metabolites in human hepatocytes. M3, M5, M8, M13 (mono-oxygenation), M14, M16, M18 (O-deethylation and sulfation), M22 and M27 appeared to be major metabolites in monkey hepatocytes. M14, M16, M18, M20 (glutathionation and dehydrogenation) and M27 appeared to be major metabolites in dog hepatocytes. M1 (O-deethylation, mono-oxygenation and glucuronidation), M3, M5, M13, M14, M16, M17 (cysteination), M18, M20, and M22 appeared to be major metabolites in rat hepatocytes. Species differences in metabolism of 7-ethoxylcoumarin in hepatocytes were observed across humans, monkeys, dogs and rats. The analysis of metabolites suggests that 7-ethoxylcoumarin may undergo 3,4-epoxidation responsible for formation of glutathione and its derived cysteine conjugates, and carboxylic acid and its glucuronides, glucosides and sulfate, besides well-known 7-hydroxycoumarin, coumarin-7-O-glucuronide, and coumarin-7-O-glucuronide. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Photocatalytic surface patterning of cellulose using diazonium salts and visible light.

PubMed

Schroll, Peter; Fehl, Charlie; Dankesreiter, Stephan; König, Burkhard

2013-10-14

Coumarin-functionalized cellulose sheets were chemically modified using a visible light catalyzed "Photo-Meerwein" arylation. Use of a photomask to pattern the surface resulted in directly visible images.

Substantial Intramolecular Charge Transfer Induces Long Emission Wavelengths and Mega Stokes Shifts in 6-Aminocoumarins

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

Liu, Xiaogang; Cole, Jacqueline M.; Xu, Zhaochao

Coumarins are deployed in numerous bioimaging and biosensing applications. Among various coumarin derivatives, 6-aminocoumarins attract increasing attention for their red-shifted emissions, mega Stokes shifts, and significant solvatochromism. These spectral characteristics together with weak emission intensities have historically been ascribed to the formation of the twisted intramolecular charge transfer (TICT) state in 6-aminocoumarins. In this work, we demonstrate that it is actually substantial intramolecular charge transfer (ICT) that is responsible for these fluorescent properties. Based on this new understanding, we reanalyzed the sensing mechanism of a 6-aminocouarmin based fluorescent probe and obtained close agreement with experimental data. Lastly, our results leadmore » to a deeper understanding of the photophysics of 6-aminocoumarins and will inspire the rational development of novel fluorescent probes.« less

A Zn(2+)-responsive highly sensitive fluorescent probe and 1D coordination polymer based on a coumarin platform.

PubMed

Kumar, Virendra; Kumar, Ajit; Diwan, Uzra; Upadhyay, K K

2013-09-28

A coumarin-based Schiff base (receptor 1) exhibited fluorescence enhancement selectively with Zn(2+) at a nanomolar level in near-aqueous medium (EtOH-H2O; 1:1, v/v). The response was instantaneous with a detection limit of 3.26 × 10(-9) M. The sensing event is supposed to incorporate a combinational effect of intramolecular charge transfer (ICT), chelation-enhanced fluorescence (CHEF) and C[double bond, length as m-dash]N isomerization mechanisms. Various spectroscopic methods, viz. IR, UV-visible, fluorescence and NMR in association with single crystal XRD studies, were used for thorough investigation of the structure of receptor 1 as well as of the sensing event. The Zn(2+) complex of receptor 1 exhibited a very nice 1D chain coordination polymeric framework in its single crystal XRD.

Fluorescent coumarin-based probe for cysteine and homocysteine with live cell application

NASA Astrophysics Data System (ADS)

Wei, Ling-Fang; Thirumalaivasan, Natesan; Liao, Yu-Cheng; Wu, Shu-Pao

2017-08-01

Cysteine (Cys) and homocysteine (Hcy) are two of important biological thiols and function as important roles in several biological processes. The development of Cys and Hcy probes will help to explore the functions of biothiols in biological systems. In this work, a new coumarin-based probe AC, containing an acryloyl moiety, was developed for Cys and Hcy detection in cells. Cys and Hcy undergo a nucleophilic addition and subsequent cyclization reaction to remove to the acryloyl group and yield a fluorescent product, 7-hydroxylcomuarin. The probe AC showed good selectivity for cysteine and homocysteine over glutathione and other amino acids and had low detection limits of 65 nM for Cys and 79 nM for Hcy, respectively. Additionally, confocal imaging experiments demonstrated that the probe AC can be applied to visualize Cys and Hcy in living cells.

Synthesis of coumarin-theophylline hybrids as a new class of anti-tubercular and anti-microbial agents.

PubMed

Mangasuli, Sumitra N; Hosamani, Kallappa M; Devarajegowda, Hirihalli C; Kurjogi, Mahantesh M; Joshi, Shrinivas D

2018-02-25

A series of novel coumarin-theophylline hybrids were synthesized and examined for their anti-tubercular activity in vitro against Mycobacterium tuberculosis H 37 Rv, anti-microbial activity in vitro against gram-positive bacteria (Staphylococcus aureus) and gram-negative bacterias (Escherichia coli, Salmonella typhi) as well as fungi (Candida albicans). The compound (3a) has shown excellent anti-tubercular activity with MIC of 0.12 μg/mL. Electron donating compounds (3a, 3f) have displayed significant anti-microbial activity. The compounds have also been precisely elucidated using single crystal X-ray diffraction techniques. Molecular docking study has been performed against 4DQU enzyme of Mycobacterium tuberculosis showed good binding interactions and is in agreement with the in vitro results. Copyright © 2018. Published by Elsevier Masson SAS.

Substantial Intramolecular Charge Transfer Induces Long Emission Wavelengths and Mega Stokes Shifts in 6-Aminocoumarins

DOE PAGES

Liu, Xiaogang; Cole, Jacqueline M.; Xu, Zhaochao

2017-06-01

Coumarins are deployed in numerous bioimaging and biosensing applications. Among various coumarin derivatives, 6-aminocoumarins attract increasing attention for their red-shifted emissions, mega Stokes shifts, and significant solvatochromism. These spectral characteristics together with weak emission intensities have historically been ascribed to the formation of the twisted intramolecular charge transfer (TICT) state in 6-aminocoumarins. In this work, we demonstrate that it is actually substantial intramolecular charge transfer (ICT) that is responsible for these fluorescent properties. Based on this new understanding, we reanalyzed the sensing mechanism of a 6-aminocouarmin based fluorescent probe and obtained close agreement with experimental data. Lastly, our results leadmore » to a deeper understanding of the photophysics of 6-aminocoumarins and will inspire the rational development of novel fluorescent probes.« less

Synthesis and biological evaluation of new coumarins bearing 2,4-diaminothiazole-5-carbonyl moiety.

PubMed

Ayati, Adileh; Oghabi Bakhshaiesh, Tayebeh; Moghimi, Setareh; Esmaeili, Rezvan; Majidzadeh-A, Keivan; Safavi, Maliheh; Firoozpour, Loghman; Emami, Saeed; Foroumadi, Alireza

2018-06-07

A series of new coumarin-containing compounds 3a-l and 4a-c was designed and synthesized based on the chalcone-type 4-amino-5-cinnamoylthiazole scaffold 2, and screened for their in vitro anticancer and antioxidant activities. Representatively, the 2-thiomorpholinothiazole derivative 3k with IC 50 values of 7.5-16.9 μg/ml demonstrated good cytotoxic effects against tested cell lines MCF-7, HepG2 and SW480. Further investigation by flow cytometric analysis confirmed that this compound induces apoptotic cell death in MCF-7 cells and cause G1-phase arrest in the cell cycle. Moreover, most of compounds had intrinsic potential for radical scavenging activity and ferric-reducing power as investigated by DPPH and FRAP assays. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Coumarin-indole conjugate donor-acceptor system: Synthesis, photophysical properties, anion sensing ability, theoretical and biological activity studies of two coumarin-indole based push-pull dyes

NASA Astrophysics Data System (ADS)

Aksungur, Tuğçe; Aydıner, Burcu; Seferoğlu, Nurgül; Özkütük, Müjgan; Arslan, Leyla; Reis, Yasemin; Açık, Leyla; Seferoğlu, Zeynel

2017-11-01

Two coumarin-indole conjugate fluorescent dyes having donor-acceptor-donor (D-A-D) (CI-1 and CI-2) were synthesized, and characterized using IR, 1H/13C NMR and HRMS. The absorption and emission properties of the dyes were determined in different solvents. The anion sensitivity and selectivity of the dyes were studied with some anions (CN-, F-, AcO-, Cl-, Br-, I-, HSO4- and H2PO4-) in DMSO, and their interaction mechanisms were evaluated by spectrophotometric and 1H NMR titration techniques. In addition, the molecular and electronic structures of CI-1, as well as the molecular complexes of CI-1, formed with the anions (F- and AcO-), were obtained theoretically and confirmed by DFT and TD-DFT calculations. CI-1 behaves as a colorimetric chemosensor for selective and sensitive detection of CN- in DMSO/H2O (9:1) over other competing anions such as F- and AcO-. However, only CN- interacts with chromophore CI-2 via Michael addition and the main absorption maxima shifts hypsochromically with an observed distinctive color change from orange to yellow. For using as a optic dye, the thermal stability properties of the dyes was determined by TGA (Thermal Gravimetric Analysis). Antimicrobial, antifungal and DNA-ligand interaction studies of the dyes were also examined. The dyes cause conformational changes on DNA and selectively bind to nucleotides of A/A and G/G.

Simultaneous micronization and purification of bioactive fraction by supercritical antisolvent technology

PubMed Central

Hiendrawan, Stevanus; Veriansyah, Bambang; Widjojokusumo, Edward; Tjandrawinata, Raymond R.

2017-01-01

Simultaneous micronization and purification of DLBS3233 bioactive fraction, a combination of two Indonesian herbals Lagerstroemia speciosa and Cinnamomum burmannii has been successfully performed via supercritical anti-solvent (SAS) technology. The objective of the present study was to investigate the effectiveness of SAS technology to micronize and reduce coumarin content of DLBS3233. The effects of four SAS process parameters, i.e. pressure, temperature, concentration and solution flow rate on particle formation were investigated. In SAS process, DLBS3233 was dissolved in dimethylformamide (DMF) as the liquid solvent. The solution was then pumped through a nozzle into a chamber simultaneously with supercritical carbon dioxide (SC-CO2) which acts as the anti-solvent, resulting in DLBS3233 precipitation. Physicochemical properties of unprocessed DLBS3233 and SAS-processed DLBS3233 particles were analyzed using scanning electron microscopy (SEM) and high pressure liquid chromatography (HPLC). Total polyphenol content (TPC) was also analyzed. Particles with mean particle size ranging from 0.107±0.028 μm to 0.298±0.138 μm were obtained by varying the process parameters. SAS-processed DLBS3233 particles showed no coumarin content in all experiments studied in this work. Results of TPC analysis revealed no significant change in SAS-processed DLBS3233 particles compared to unprocessed DLBS3233. Nano-sized DLBS3233 particles with no coumarin content have been successfully produced using SAS process. This study demonstrates the ability of SAS for processing herbal medicine in single step process. PMID:28516056

The genus Pterocaulon (Asteraceae) - A review on traditional medicinal uses, chemical constituents and biological properties.

PubMed

Medeiros-Neves, Bruna; Teixeira, Helder Ferreira; von Poser, Gilsane Lino

2018-06-15

Species of the genus Pterocaulon (Asteraceae) are used in different parts of the world for mainly to treat skin and liver diseases, as well as disorders of the respiratory system, among others. This review aims to discuss the present state of the art concerning the ethnobotanical uses, secondary metabolites and biological effects of Pterocaulon species and their chemical components. The available information on the genus Pterocaulon was gathered from scientific databases (Web of Science, Pubmed, ScienceDirect, Scopus, ChemSpider, SciFinder ACS Publications, Wiley Online Library). Information was also obtained from local publications, M.Sc. and Ph.D. dissertations. All studies on the ethnobotany, phytochemistry, pharmacology and toxicology of the plants until December 2017 were included in this review. Approximately 40 coumarins and 30 flavonoids have been isolated from Pterocaulon species. Coumarins have been considered the chemotaxonomic markers in the genus and the most active components. Pharmacological studies carried out with extracts and isolated compounds revealed in vitro bioactivities that include antifungal, antiviral, and cytotoxicity. Most of the pharmacological investigations were not correlated with traditional uses of the plants. Pterocaulon species, a rich source of coumarins, have great ethnomedical potential. Nevertheless, further studies into the pharmacological activities are necessary since none of the purported effects of these plants was fully assessed. In-depth research regarding the toxicity are also required to ensure the safety of these medicinal plants. Copyright © 2018 Elsevier Ireland Ltd. All rights reserved.

Simultaneous Determination of Decursin, Decursinol Angelate, Nodakenin, and Decursinol of Angelica gigas Nakai in Human Plasma by UHPLC-MS/MS: Application to Pharmacokinetic Study.

PubMed

Kim, Sook-Jin; Ko, Se-Mi; Choi, Eun-Jeong; Ham, Seong-Ho; Kwon, Young-Dal; Lee, Yong-Bok; Cho, Hea-Young

2018-04-26

Coumarins in Cham-dang-gwi, the dried root of Angelica gigas Nakai (AGN), possess pharmacological effects on anemia, pain, infection, and articular rheumatism. The AGN root containes decursin (D), decursinol angelate (DA), nodakenin, and decursinol (DOH), a major metabolite of D and DA. The aim of this study was to develop a simultaneous determination method for these four coumarins in human plasma using ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Chromatographic separation was performed on dual columns (Kinetex ® C 18 column and Capcell core C 18 column) with mobile phase consisting of water and acetonitrile at a flow rate of 0.3 mL/min using gradient elution. Multiple reaction monitoring was operated in positive ion mode with precursors to product ion transition values of m / z 328.9→228.8, 328.9→228.9, 409.4→248.8, and 246.8→212.9 to measure D, DA, nodakenin, and DOH, respectively. Linear calibration curves were fitted over concentration range of 0.05⁻50 ng/mL for these four components, with correlation coefficient greater than 0.995. Inter- and intra-day accuracies were between 90.60% and 108.24%. These precisions were within 11.19% for all components. The established method was then applied to a pharmacokinetic study for the four coumarins after usual dosing in Korean subjects.

Poly(vinyl benzoate) nanoparticles for molecular delivery: Studies on their preparation and in vitro properties.

PubMed

Labruère, Raphaël; Sicard, Renaud; Cormier, Ryan; Turos, Edward; West, Leigh

2010-12-01

The preparation and properties of poly(vinyl benzoate) nanoparticle suspensions as molecular carriers are described for the first time. These nanoparticles can be formed by nanoprecipitation of commercial poly(vinyl benzoate) in water using Pluronic F68 as surfactant, to create spherical nanostructures measuring 200-250nm in diameter. These nanoparticles are stable in phosphate buffer and blood serum, and only slowly degrade in the presence of esterases. Pluronic F68 stabilizes the nanoparticle and also protects it from enzymatic degradation. Up to 1.6% by weight of a lipid-soluble molecule such as coumarin-6 can be introduced into the nanoparticle during nanoprecipitation, compared to a water-soluble compound (5(6)-carboxyfluorescein) which gave almost no loading. Kinetics experiments in phosphate buffer indicate that 78% of the coumarin-6 was encapsulated within the polymer matrix of the nanoparticle, and the residual 22% of coumarin-6 was surface-bound and quickly released. The nanoparticles are non-toxic in vitro towards human epithelial cells (IC(50)>1000μg/mL) and primary bovine aortic endothelial cells (IC(50)>500μg/mL), and non-bactericidal against a selection of representative test microbes (MIC >250μg/mL). These properties suggest that the poly(vinyl benzoate) nanoparticles may be suitable carriers for molecular delivery of lipophilic small molecules such as pharmaceutical and imaging agents. Copyright © 2010. Published by Elsevier B.V.

Dye Aggregation and Complex Formation Effects in 7-(Diethylamino)-coumarin-3-carboxylic Acid

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

Liu, Xiaogang; Cole, Jacqueline M.; Chow, Philip C. Y.

2014-06-19

7-(Diethylamino)-coumarin-3-carboxylic acid (1) has been used as a laser dye, fluorescent label, and biomedical inhibitor in many different applications. Although this dye is typically used in the solution phase, it is prone to molecular aggregation, resulting in many inconsistent optoelectronic properties being reported in the literature. In this paper, the UV—vis absorption and fluorescence spectra of 1 are investigated in three representative solvents: cyclohexane [nonpolar and non-hydrogen bonding (NHB)], ethanol (moderately polar and hydrogen-bond accepting/donating), and DMSO (strongly polar and hydrogen-bond accepting). These experimental results, in conjunction with (time-dependent) density functional theory (DFT/TDDFT) based quantum calculations, have led to themore » identification of the J-aggregates of 1, and rationalized its different aggregation characteristic in cyclohexane in contrast to that of another similar compound, coumarin 343. We show here that these aggregates are largely responsible for the anomalous optoelectronic properties of this compound. In addition, DFT calculations and 1H NMR spectroscopy measurements suggest that the intramolecular hydrogen bond in 1 could be "opened up" in hydrogen-bond accepting solvents, affording significant molecular conformational changes and complex formation effects. The comprehensive understanding of the molecular aggregation and complex formation mechanisms of 1 acquired through this work forms a foundation for the knowledge-based molecular design of organic dyes with tailored aggregation tendencies or anti-aggregation characteristics to cater for different opapplications.« less

Simultaneous micronization and purification of bioactive fraction by supercritical antisolvent technology.

PubMed

Hiendrawan, Stevanus; Veriansyah, Bambang; Widjojokusumo, Edward; Tjandrawinata, Raymond R

2017-01-01

Simultaneous micronization and purification of DLBS3233 bioactive fraction, a combination of two Indonesian herbals Lagerstroemia speciosa and Cinnamomum burmannii has been successfully performed via supercritical anti-solvent (SAS) technology. The objective of the present study was to investigate the effectiveness of SAS technology to micronize and reduce coumarin content of DLBS3233. The effects of four SAS process parameters, i.e. pressure, temperature, concentration and solution flow rate on particle formation were investigated. In SAS process, DLBS3233 was dissolved in dimethylformamide (DMF) as the liquid solvent. The solution was then pumped through a nozzle into a chamber simultaneously with supercritical carbon dioxide (SC-CO2) which acts as the anti-solvent, resulting in DLBS3233 precipitation. Physicochemical properties of unprocessed DLBS3233 and SAS-processed DLBS3233 particles were analyzed using scanning electron microscopy (SEM) and high pressure liquid chromatography (HPLC). Total polyphenol content (TPC) was also analyzed. Particles with mean particle size ranging from 0.107±0.028 μ m to 0.298±0.138 μ m were obtained by varying the process parameters. SAS-processed DLBS3233 particles showed no coumarin content in all experiments studied in this work. Results of TPC analysis revealed no significant change in SAS-processed DLBS3233 particles compared to unprocessed DLBS3233. Nano-sized DLBS3233 particles with no coumarin content have been successfully produced using SAS process. This study demonstrates the ability of SAS for processing herbal medicine in single step process.

Photocatalytic Surface Patterning of Cellulose using Diazonium Salts and Visible Light

PubMed Central

Schroll, Peter; Fehl, Charlie; Dankesreiter, Stephan

2013-01-01

Coumarin-functionalized cellulose sheets were chemically modified using a visible light catalyzed “Photo-Meerwein” arylation. Use of a photomask to pattern the surface resulted in directly visible images. PMID:23963264

Biological activities of a Turkish medicinal plant, Prangos platychlaena.

PubMed

Ulubelen, A; Topcu, G; Tan, N; Olçal, S; Johansson, C; Uçer, M; Birman, H; Tamer, S

1995-03-01

Prangos platychlaena has been used in traditional medicine in eastern Turkey. It stops bleeding and heals the scars when applied externally. When the isolated coumarins were tested against bacterial strains, only a slight activity was obtained.

Non-uniform Continuum Model for Solvated Species Based on Frozen-Density Embedding Theory: The Study Case of Solvatochromism of Coumarin 153.

PubMed

Shedge, Sapana V; Zhou, Xiuwen; Wesolowski, Tomasz A

2014-09-01

Recent application of the Frozen-Density Embedding Theory based continuum model of the solvent, which is used for calculating solvatochromic shifts in the UV/Vis range, are reviewed. In this model, the solvent is represented as a non-uniform continuum taking into account both the statistical nature of the solvent and specific solute-solvent interactions. It offers, therefore, a computationally attractive alternative to methods in which the solvent is described at atomistic level. The evaluation of the solvatochromic shift involves only two calculations of excitation energy instead of at least hundreds needed to account for inhomogeneous broadening. The present review provides a detailed graphical analysis of the key quantities of this model: the average charge density of the solvent (<ρB>) and the corresponding Frozen-Density Embedding Theory derived embedding potential for coumarin 153.

A novel coumarin-pyrazole-triazine based fluorescence chemosensor for fluoride detection via deprotonation process: Experimental and theoretical studies

NASA Astrophysics Data System (ADS)

Yalçın, Ergin; Alkış, Meltem; Seferoğlu, Nurgül; Seferoğlu, Zeynel

2018-03-01

A novel fluorescence coumarin-pyrazole-triazine based chemosensor (CPT) bearing 5-hydroxypyrazole as a receptoric part was synthesized and characterized by using IR, 1H/13C NMR and HRMS for the purpose of recognition of anions in DMSO. The most stable tautomeric form of CPT was determined by experimental techniques and theoretical calculations. The selectivity and sensitivity of CPT towards anions (CN-, F-, Cl-, Br-, I-, AcO-, HSO4-, H2PO4- and ClO4-) were determined using spectrophotometric and 1H NMR titration techniques as the experimental approach, and the results were explained by employing theoretical calculations. It was found to be suitable for the selective detection of F- in the presence of CN- and AcO- as competing anions. In addition, CPT exhibits significant "light-up" effect after interaction with TFA in CH2Cl2.

AD6 (8-monochloro-3-beta-diethylamino-ethyl-4-methyl-7-ethoxycarbonyl-meth oxy coumarin) inhibits the release of arachidonic acid in human platelets stimulated by thrombin

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

Porcellati, S.; Costantini, V.; Prosdocimi, M.

1987-07-01

The coumarin derivative AD6 is known to inhibit platelet aggregation and release and it possesses vasodilatory properties on coronary arteries of laboratory animals. Furthermore, the inhibition of the production of TxB2 from endogenous substrates after stimulation of human platelets with collagen has been demonstrated. The present report demonstrates that AD6 inhibits the production of labeled arachidonic acid and diglycerides from phospholipids of platelets stimulated with thrombin. This effect is dose-dependent and is already evident at a concentration of the drug (25 microM) which is unable to prevent the aggregation. Apparently, AD6 inhibits the release of arachidonic acid from phosphatidylinositol andmore » choline phosphoglycerides which are the main sources of the substrate for the synthesis of prostaglandins and thromboxanes.« less

Pavietin, a coumarin from Aesculus pavia with antifungal activity.

PubMed

Curir, Paolo; Galeotti, Francesco; Dolci, Marcello; Barile, Elisa; Lanzotti, Virginia

2007-10-01

A new prenylated coumarin, S-6-[2-(hydroxymethyl)butoxy]-7-hydroxy-4-methyl-2 H-chromen-2-one ( 1), named pavietin, has been isolated from the leaves of an Aesculus pavia genotype along with three known flavonol glycosides, quercetin 3- O-alpha-rhamnoside (quercitrin, 2), quercetin 3- O-alpha-arabinoside ( 3), and isorhamnetin 3- O-alpha-arabinoside (distichin, 4). The chemical structure of compound 1 was determined by chemical and spectroscopic methods, inclusive of UV, MS, and 1D and 2D NMR experiments. It showed appreciable antimicrobial properties against several pathogens, displaying a significant antifungal activity toward one of the main fungal parasites of Aesculus species, Guignardia aesculi. The same biological tests performed with a mixture of flavonoids 2- 4 resulted in weak or no activity. Compound 1 was undetectable in Aesculus hippocastanum, a closely related species lacking resistance to fungal pathogens. The possible role of 1 in plant resistance is discussed.

Design, synthesis and evaluation of novel tacrine-coumarin hybrids as multifunctional cholinesterase inhibitors against Alzheimer's disease.

PubMed

Xie, Sai-Sai; Wang, Xiao-Bing; Li, Jiang-Yan; Yang, Lei; Kong, Ling-Yi

2013-06-01

A series of tacrine-coumarin hybrids (8a-t) were designed, synthesized and evaluated as multifunctional cholinesterase (ChE) inhibitors against Alzheimer's disease (AD). The screening results showed that most of them exhibited a significant ability to inhibit ChE and self-induced β-amyloid (Aβ) aggregation, and to act as metal chelators. Especially, 8f displayed the greatest ability to inhibit acetylcholinesterase (AChE, IC50 = 0.092 μM) and Aβ aggregation (67.8%, 20 μM). It was also a good butyrylcholinesterase inhibitor (BuChE, IC50 = 0.234 μM) and metal chelator. Besides, kinetic and molecular modeling studies indicated that 8f was a mixed-type inhibitor, binding simultaneously to active, peripheral and mid-gorge sites of AChE. These results suggested that 8f might be an excellent multifunctional agent for AD treatment. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Decursin from Angelica gigas mitigates amnesia induced by scopolamine in mice.

PubMed

Kang, So Young; Lee, Ki Yong; Park, Mi Jung; Kim, Young Chul; Markelonis, George J; Oh, Tae H; Kim, Young Choong

2003-01-01

We previously reported that a total methanolic extract of the underground part of Angelica gigas Nakai (Umbelliferae) (here-in-after abbreviated AG) significantly inhibited acetylcholinesterase (AChE) activity. We characterized 12 coumarin derivatives including both decursin and decursinol from extracts of AG. In this study, we evaluated the anti-amnestic activity of decursin, a major coumarin constituent isolated from AG, in vivo using ICR mice with amnesia induced by scopolamine (1 mg/kg body weight, s.c.). Decursin, when administered to mice at 1 and 5 mg/kg body weight i.p., significantly ameliorated scopolamine-induced amnesia as measured in both the passive avoidance test and the Morris water maze test. Moreover, decursin significantly inhibited AChE activity by 34% in the hippocampus of treated mice. These results indicate that decursin may exert anti-amnestic activity in vivo through inhibition of AChE activity in the hippocampus.

Synthesis and anticholinesterase activity of coumarin-3-carboxamides bearing tryptamine moiety.

PubMed

Ghanei-Nasab, Samaneh; Khoobi, Mehdi; Hadizadeh, Farzin; Marjani, Azam; Moradi, Alireza; Nadri, Hamid; Emami, Saeed; Foroumadi, Alireza; Shafiee, Abbas

2016-10-04

A number of N-(2-(1H-indol-3-yl)ethyl)-2-oxo-2H-chromene-3-carboxamides were synthesized and tested against AChE and BuChE. The in vitro assessment of the synthesized compounds 4a-o revealed that most of them had significant activity toward AChE. The SAR study demonstrated that the introduction of benzyloxy moiety on the 7-position of coumarin scaffold can improve the anti-AChE activity. The best result was obtained with 7-(4-fluorobenzyl)oxy moiety in the case of compound 4o, displaying IC50 value of 0.16 μM. Based on the docking study of AChE, the prototype compound 4o was laid across the active site and occupied both peripheral anionic site (PAS) and catalytic anionic site (CAS). Copyright © 2016 Elsevier Masson SAS. All rights reserved.

A highly selective fluorescent probe for the detection of hypochlorous acid in tap water and living cells.

PubMed

Wang, Xiao; Zhou, Yanmei; Xu, Chenggong; Song, Haohan; Li, Li; Zhang, Junli; Guo, Meixia

2018-06-03

A turn-on fluorescent probe (DAME) for sensing hypochlorous acid (HClO) with excellent selectivity was presented. The fluorescent probe was composed of coumarin derivative as the fluorophore and dimethylcarbamothioic chloride group with a sulfide moiety as modulator. Additionally, the sulfide moiety would be oxidized by HClO, and then free dye of coumarin derivate was released and exhibited significant fluorescence. In addition, the probe could respond to HClO in solutions within 60 s and the limit of detection was down to 34.75 nM. Moreover, the probe was used for the detection of HClO in tap water through the home-made test paper. And confocal images confirmed that probe DAME could be used for recognizing HClO in living cells. Copyright © 2017 Elsevier B.V. All rights reserved.

Sweet clover production and agronomy.

PubMed

Goplen, B P

1980-05-01

Sweetclover has a notorious reputation for causing "sweetclover disease" when improperly cured. In spite of this, however, sweetclover remains a useful forage legume with valuable agronomic traits. It is drought-resistant and well adapted to Western Canada. Sweetclover is the highest yielding legume forage in this region and is valuable in soil improvement, silage, hay and pasture production and a prized crop for the honey producer. It is the most saline-tolerant of the legumes and is particularly useful on saline "white alkali" soils where cereals and other crops cannot grow. Special precautions are necessary to avoid spoilage and concomitant dicoumarol formation in preserving sweetclover hay and silage. Feeding recommendations are suggested for the safe utilization of spoiled forage. Low coumarin cultivars of sweetclover are completely safe and will not result in sweetclover disease despite spoilage. The breeding program at Saskatoon is expected to produce a new low coumarin (yellow flowered) sweetclover cultivar within the next two years.

Theoretical studies on absorption, emission, and resonance Raman spectra of Coumarin 343 isomers

NASA Astrophysics Data System (ADS)

Wu, Wenpeng; Cao, Zexing; Zhao, Yi

2012-03-01

The vibrationally resolved spectral method and quantum chemical calculations are employed to reveal the structural and spectral properties of Coumarin 343 (C343), an ideal candidate for organic dye photosensitizers, in vacuum and solution. The results manifest that the ground-state energies are dominantly determined by different placements of hydrogen atom in carboxylic group of C343 conformations. Compared to those in vacuum, the electronic absorption spectra in methanol solvent show a hyperchromic property together with the redshift and blueshift for the neutral C343 isomers and their deprotonated anions, respectively. From the absorption, emission, and resonance Raman spectra, it is found that the maximal absorption and emission come from low-frequency modes whereas the high-frequency modes have high Raman activities. The detailed spectra are further analyzed for the identification of the conformers and understanding the potential charge transfer mechanism in their photovoltaic applications.

Alteration of Escherichia coli topoisomerase IV to novobiocin resistance.

PubMed

Hardy, Christine D; Cozzarelli, Nicholas R

2003-03-01

DNA gyrase and topoisomerase IV (topo IV) are the two essential type II topoisomerases of Escherichia coli. Gyrase is responsible for maintaining negative supercoiling of the bacterial chromosome, whereas topo IV's primary role is in disentangling daughter chromosomes following DNA replication. Coumarins, such as novobiocin, are wide-spectrum antimicrobial agents that primarily interfere with DNA gyrase. In this work we designed an alteration in the ParE subunit of topo IV at a site homologous to that which confers coumarin resistance in gyrase. This parE mutation renders the encoded topo IV approximately 40-fold resistant to inhibition by novobiocin in vitro and imparts a similar resistance to inhibition of topo IV-mediated relaxation of supercoiled DNA in vivo. We conclude that topo IV is a secondary target of novobiocin and that it is very likely to be inhibited by the same mechanism as DNA gyrase.

Viscosity induced emission of red-emitting NLOphoric coumarin morpholine-thiazole hybrid styryl dyes as FMRs: Consolidated experimental and theoretical approach

NASA Astrophysics Data System (ADS)

Avhad, Kiran C.; Patil, Dinesh S.; Chitrambalam, S.; Sreenath, M. C.; Joe, I. Hubert; Sekar, Nagaiyan

2018-05-01

Four new coumarin hybrid styryl dyes are synthesized by condensing 4-(7-(diethylamino)-2-oxo-2H-chromen-3-yl)-2-morpholinothiazole-5-carbaldehyde with dicyanovinylene containing active methylene intermediates and their linear and non-linear optical properties are studied. The dye having dicyanovinylene-isophorone acceptor displayed a large Stokes shift of 3702-4795 cm-1 in non-polar to polar solvent respectively. The dyes exhibit a good charge transfer characteristics and positive emission solvatochromism (∼50 nm-72 nm) in non-polar to a polar solvent which is well supported by multi-linear regression analysis. Viscosity induced enhancement study in ethanol/polyethylene glycol-400 system shows 2.71-6.78 fold increase in emission intensity. The intra and twisted-intramolecular charge transfer (ICT-TICT) characteristics were established using emission solvatochromism, polarity plots, generalised Mullikan-Hush (GMH) analysis and optimized geometry. A dye having the highest charge transfer dipole moment relatively possess the maximum two-photon absorption cross-section area (KK-1 = 165-207 GM) which was established using theoretical two-level model. The NLO properties have been investigated employing solvatochromic and computational methods and were found to be directly proportional to the polarity of the solvent. Z-scan results reveal that the dyes KK-1 and KK-2 possesses reverse saturable kind of behaviour whereas KK-3 and KK-4 show saturable kind of behaviour. From the experimental and theoretical data, these coumarin thiazole hybrid dyes can be considered as promising candidates for FMR and NLOphores.

Coumarin-modified microporous-mesoporous Zn-MOF-74 showing ultra-high uptake capacity and photo-switched storage/release of U(VI) ions.

PubMed

Zhang, Le; Wang, Lin Lin; Gong, Le Le; Feng, Xue Feng; Luo, Ming Biao; Luo, Feng

2016-07-05

Driven by an energy crisis but consequently puzzled by various environmental problems, uranium, as the basic material of nuclear energy, is now receiving extensive attentions. In contrast to numerous sorbents applied in this field, metal-organic framework (MOFs), as a renovated material platform, has only recently been developed. How to improve the adsorption capacity of MOF materials towards U(VI) ions, as well as taking advantage of the nature of these MOFs to design photo-switched behaviour for photo-triggered storage/release of U(VI) ions are at present urgent problems and great challenges to be solved. Herein, we show a simple and facile method to target the goal. Through coordination-based post-synthetic strategy, microporous- mesoporous Zn-MOF-74 was easily functionalized by grafting coumarin on coordinatively unsaturated Zn(II) centers, yielding a series of coumarin-modified Zn-MOF-74 materials. The obtained samples displayed ultra-high adsorption capacity for U(VI) ions from water at pH value of 4 with maximum adsorption capacities as high as 360 mg/g (the record value in MOFs) and a remarkable photo-switched capability of 50 mg/g at pH value of 4. To the best of knowledge, and in contrast to the well-known photo-switched behaviour towards CO2, dye (propidium iodide), as well as fluorescence observed in MOFs, this is the first study that shows a photo-switched behaviour towards radioactive U(VI) ions in aqueous solution. Copyright © 2016 Elsevier B.V. All rights reserved.

Evaluation of phototoxic potential of aerial components of the fig tree against human melanoma.

PubMed

Conforti, F; Menichini, G; Zanfini, L; Tundis, R; Statti, G A; Provenzano, E; Menichini, F; Somma, F; Alfano, C

2012-06-01

To date, Ficus carica L. cultivar Dottato (F. carica) has not been studied from a phototoxic point of view. In the present work, aerial components of F. carica from Italy, were examined to assess their antioxidant and phototoxic activity on human melanoma cells. A relationship between antioxidant, phototoxic activities and chemical composition has also been investigated. Coumarin and fatty acid content in F. carica leaves, bark and woody parts were examined and compared by capillary GC and GC/MS. Polyphenolic content was also determined. Linoleic acid peroxidation and DPPH test were used to assess antioxidant activities, and MTT assay was used to evaluate anti-proliferative activity, on C32 human melanoma cells, after irradiation with a UVA dose of 1.08 J/cm(2). Leaves demonstrated the best antioxidant and anti-proliferative activity in comparison to bark and wood. In particular, leaves were shown to possess the highest anti-radical activity and inhibition of peroxidation, with IC(50) values of 64 and 1.48 μg/ml respectively. The leaves had highest anti-proliferative activity with IC(50) value of 3.92 μg/ml. The phytochemical investigation revealed different composition between the coumarins, psoralen and bergapten, fatty acids, polyphenols and flavonoid content among plant parts. Data obtained indicate that this type of fig tree may constitute an excellent source of bioactive compounds, such as phenolics, coumarins and fatty acids. This study offers a new perspective in developing others formulations potentially useful in photodynamic therapy for treatment of non-melanoma skin cancers. © 2012 Blackwell Publishing Ltd.

A hybrid of coumarin and phenylsulfonylfuroxan induces caspase-dependent apoptosis and cytoprotective autophagy in lung adenocarcinoma cells.

PubMed

Wang, Qian; Guo, Yalan; Jiang, Shanshan; Dong, Mengxue; Kuerban, Kudelaidi; Li, Jiyang; Feng, Meiqing; Chen, Ying; Ye, Li

2018-01-15

Lung adenocarcinoma is the most primary histologic subtype of non-small cell lung cancer (NSCLC). Compound 8b, a novel coumarin derivative with phenylsulfonylfuroxan group, shows significant antiproliferation activity against lung adenocarcinoma cell with low toxicity. This study aims to uncover the potential of compound 8b in relation to apoptosis as well as autophagy induction in lung adenocarcinoma cells. The cytotoxicity and apoptosis of A549 and H1299 cells induced by compound 8b were detected by MTT, microscope and western blot analysis. Autophagy was determined by TEM, confocal microscopy and western blot analysis. Akt/mTOR and Erk signaling pathway were also examined by western blot analysis. First, significant growth inhibition and caspase-dependent apoptosis were observed in compound 8b-treated A549 and H1299 cells. Then, we confirmed compound 8b-induced autophagy by autophagosomes formation, upregulated expression of autophagy-related protein LC3-II and autophagic flux. Importantly, abolishing autophagy using inhibitors and ATG5 siRNA enhanced the cytotoxicity of compound 8b, indicating the cytoprotective role of autophagy in lung adenocarcinoma. Further mechanistic investigations suggested that Akt/mTOR and Erk signaling pathways contributed to autophagy induction by compound 8b. This results demonstrate that compound 8b induces caspase-dependent apoptosis as well as cytoprotective autophagy in lung adenocarcinoma cells, which may provide scientific evidence for developing this furoxan-based NO-releasing coumarin derivative as a potential anti-lung adenocarcinoma therapeutic agents. Copyright © 2017 Elsevier GmbH. All rights reserved.

The high-resolution crystal structure of a 24-kDa gyrase B fragment from E. coli complexed with one of the most potent coumarin inhibitors, clorobiocin.

PubMed

Tsai, F T; Singh, O M; Skarzynski, T; Wonacott, A J; Weston, S; Tucker, A; Pauptit, R A; Breeze, A L; Poyser, J P; O'Brien, R; Ladbury, J E; Wigley, D B

1997-05-01

Coumarin antibiotics, such as clorobiocin, novobiocin, and coumermycin A1, inhibit the supercoiling activity of gyrase by binding to the gyrase B (GyrB) subunit. Previous crystallographic studies of a 24-kDa N-terminal domain of GyrB from E. coli complexed with novobiocin and a cyclothialidine analogue have shown that both ligands act by binding at the ATP-binding site. Clorobiocin is a natural antibiotic isolated from several Streptomyces strains and differs from novobiocin in that the methyl group at the 8 position in the coumarin ring of novobiocin is replaced by a chlorine atom, and the carbamoyl at the 3' position of the noviose sugar is substituted by a 5-methyl-2-pyrrolylcarbonyl group. To understand the difference in affinity, in order that this information might be exploited in rational drug design, the crystal structure of the 24-kDa GyrB fragment in complex with clorobiocin was determined to high resolution. This structure was determined independently in two laboratories, which allowed the validation of equivalent interpretations. The clorobiocin complex structure is compared with the crystal structures of gyrase complexes with novobiocin and 5'-adenylyl-beta, gamma-imidodiphosphate, and with information on the bound conformation of novobiocin in the p24-novobiocin complex obtained by heteronuclear isotope-filtered NMR experiments in solution. Moreover, to understand the differences in energetics of binding of clorobiocin and novobiocin to the protein, the results from isothermal titration calorimetry are also presented.

Novel CoIII complexes containing fluorescent coumarin-N-acylhydrazone hybrid ligands: Synthesis, crystal structures, solution studies and DFT calculations

NASA Astrophysics Data System (ADS)

Areas, Esther S.; Bronsato, Bruna Juliana da S.; Pereira, Thiago M.; Guedes, Guilherme P.; Miranda, Fábio da S.; Kümmerle, Arthur E.; da Cruz, Antônio G. B.; Neves, Amanda P.

2017-12-01

A series of new CoIII complexes of the type [Co(dien)(L1 -L3)]ClO4 (1-3), containing fluorescent coumarin-N-acylhydrazonate hybrid ligands, (E)-N‧-(1-(7-oxido-2-oxo-2H-chromen-3-yl)ethylidene)-4-R-benzohydrazonate [where R = H (L12 -), OCH3 (L22 -) or Cl (L32 -)], were obtained and isolated in the low spin CoIII configuration. Single-crystal X-ray diffraction showed that the coumarin-N-acylhydrazones act as tridentate ligands in their deprotonated form (L2 -). The cation (+ 1) complexes contain a diethylenetriamine (dien) as auxiliary ligand and their structures were calculated by DFT studies which were also performed for the CoII (S = 1/2 and S = 3/2) configurations. The LS CoII (S = 1/2) concentrated the spin density on the O-Co-O axis while the HS CoII (S = 3/2) exhibited a broad spin density distribution around the metallic center. Cyclic voltammetry studies showed that structural modifications made in the L2 - ligands caused a slight influence on the electronic density of the metal center, and the E1/2 values for the CoIII/CoII redox couple increased following the electronic effect of the R-substituent, in the order: 2 (R = OCH3) < 1 (R = H) < 3 (R = Cl). The theoretical redox potentials (E°) of the process CoIII → CoII were calculated for both CoII spin states (S = 1/2 and S = 3/2) and a better correlation was found for CoIII → CoII (S = 1/2), compared with experimental values vs SHE (E°calc = - 0.37, - 0.36 and - 0.32 V vs E°exp. = - 0.371, - 0.406 and - 0.358 V, for 1-3 respectively). Complexes 1-3 exhibited a very intense absorption band around 470 nm, assigned by DFT calculations as π-π* transitions from the delocalized coumarin-N-acylhydrazone system. 1-3 were very stable in MeOH for several days. Likewise, 1-3 were stable in phosphate buffer containing sodium ascorbate after 15 h, which was attributed to the high chelate effect and σ-donor ability of the L2 - and dien ligands.

Antiviral effect of compounds derived from the seeds of Mammea americana and Tabernaemontana cymosa on Dengue and Chikungunya virus infections.

PubMed

Gómez-Calderón, Cecilia; Mesa-Castro, Carol; Robledo, Sara; Gómez, Sergio; Bolivar-Avila, Santiago; Diaz-Castillo, Fredyc; Martínez-Gutierrez, Marlen

2017-01-18

The transmission of Dengue virus (DENV) and Chikungunya virus (CHIKV) has increased worldwide, due in part to the lack of a specific antiviral treatment. For this reason, the search for compounds with antiviral potential, either as licensed drugs or in natural products, is a research priority. The objective of this study was to identify some of the compounds that are present in Mammea americana (M. americana) and Tabernaemontana cymosa (T. cymosa) plants and, subsequently, to evaluate their cytotoxicity in VERO cells and their potential antiviral effects on DENV and CHIKV infections in those same cells. Dry ethanolic extracts of M. americana and T. cymosa seeds were subjected to open column chromatographic fractionation, leading to the identification of four compounds: two coumarins, derived from M. americana; and lupeol acetate and voacangine derived from T. cymosa.. The cytotoxicity of each compound was subsequently assessed by the MTT method (at concentrations from 400 to 6.25 μg/mL). Pre- and post-treatment antiviral assays were performed at non-toxic concentrations; the resulting DENV inhibition was evaluated by Real-Time PCR, and the CHIKV inhibition was tested by the plating method. The results were analyzed by means of statistical analysis. The compounds showed low toxicity at concentrations ≤ 200 μg/mL. The compounds coumarin A and coumarin B, which are derived from the M. americana plant, significantly inhibited infection with both viruses during the implementation of the two experimental strategies employed here (post-treatment with inhibition percentages greater than 50%, p < 0.01; and pre-treatment with percentages of inhibition greater than 40%, p < 0.01). However, the lupeol acetate and voacangine compounds, which were derived from the T. cymosa plant, only significantly inhibited the DENV infection during the post-treatment strategy (at inhibition percentages greater than 70%, p < 0.01). In vitro, the coumarins are capable of inhibiting infection by DENV and CHIKV (with inhibition percentages above 50% in different experimental strategies), which could indicate that these two compounds are potential antivirals for treating Dengue and Chikungunya fever. Additionally, lupeol acetate and voacangine efficiently inhibit infection with DENV, also turning them into promising antivirals for Dengue fever.

A reversible ratiometric sensor for intracellular Cu2+ imaging: metal coordination-altered FRET in a dual fluorophore hybrid.

PubMed

Chen, Yuncong; Zhu, Chengcheng; Cen, Jiajie; Li, Jing; He, Weijiang; Jiao, Yang; Guo, Zijian

2013-09-07

ICT fluorophore benzoxadiazole with its electron-donating group modified as a Cu(2+) chelator was conjugated with coumarin to construct a new ratiometric sensor with reversible intracellular Cu(2+) imaging ability.

21 CFR 189.130 - Coumarin.

Code of Federal Regulations, 2011 CFR

2011-04-01

..., C9H6O2. It is found in tonka beans and extract of tonka beans, among other natural sources, and is also... constituent of tonka beans or tonka extract is deemed to be adulterated under the act, based upon an order...

SKLB060 Reversibly Binds to Colchicine Site of Tubulin and Possesses Efficacy in Multidrug-Resistant Cell Lines.

PubMed

Yan, Wei; Yang, Tao; Yang, Jianhong; Wang, Taijin; Yu, Yamei; Wang, Yuxi; Chen, Qiang; Bai, Peng; Li, Dan; Ye, Haoyu; Qiu, Qiang; Zhou, Yongzhao; Hu, Yiguo; Yang, Shengyong; Wei, Yuquan; Li, Weimin; Chen, Lijuan

2018-05-22

Many tubulin inhibitors are in clinical use as anti-cancer drugs. In our previous study, a novel series of 4-substituted coumarins derivatives were identified as novel tubulin inhibitors. Here, we report the anti-cancer activity and underlying mechanism of one of the 4-substituted coumarins derivatives (SKLB060). The anti-cancer activity of SKLB060 was tested on 13 different cancer cell lines and four xenograft cancer models. Immunofluorescence staining, cell cycle analysis, and tubulin polymerization assay were employed to study the inhibition of tubulin. N, N '-Ethylenebis(iodoacetamide) assay was used to measure binding to the colchicine site. Wound-healing migration and tube formation assays were performed on human umbilical vascular endothelial cells to study anti-vascular activity (the ability to inhibit blood vessel growth). Mitotic block reversibility and structural biology assays were used to investigate the SKLB060-tubulin bound model. SKLB060 inhibited tubulin polymerization and subsequently induced G2/M cell cycle arrest and apoptosis in cancer cells. SKLB060 bound to the colchicine site of β-tubulin and showed antivascular activity in vitro. Moreover, SKLB060 induced reversible cell cycle arrest and reversible inhibition of tubulin polymerization. A mitotic block reversibility assay showed that the effects of SKLB060 have greater reversibility than those of colcemid (a reversible tubulin inhibitor), indicating that SKLB060 binds to tubulin in a totally reversible manner. The crystal structures of SKLB060-tubulin complexes confirmed that SKLB060 binds to the colchicine site, and the natural coumarin ring in SKLB060 enables reversible binding. These results reveal that SKLB060 is a powerful and reversible microtubule inhibitor that binds to the colchicine site and is effective in multidrug-resistant cell lines. © 2018 The Author(s). Published by S. Karger AG, Basel.

Determination of eugenol, anethole, and coumarin in the mainstream cigarette smoke of Indonesian clove cigarettes.

PubMed

Polzin, Gregory M; Stanfill, Stephen B; Brown, Candace R; Ashley, David L; Watson, Clifford H

2007-10-01

Indonesian clove cigarettes (kreteks), typically have the appearance of a conventional domestic cigarette. The unique aspects of kreteks are that in addition to tobacco they contain dried clove buds (15-40%, by wt.), and are flavored with a proprietary "sauce". Whereas the clove buds contribute to generating high levels of eugenol in the smoke, the "sauce" may also contribute other potentially harmful constituents in addition to those associated with tobacco use. We measured levels of eugenol, trans-anethole (anethole), and coumarin in smoke from 33 brands of clove-flavored cigarettes (filtered and unfiltered) from five kretek manufacturers. In order to provide information for evaluating the delivery of these compounds under standard smoking conditions, a quantification method was developed for their measurement in mainstream cigarette smoke. The method allowed collection of mainstream cigarette smoke particulate matter on a Cambridge filter pad, extraction with methanol, sampling by automated headspace solid-phase microextraction, and subsequent analysis using gas chromatography/mass spectrometry. The presence of these compounds was confirmed in the smoke of kreteks using mass spectral library matching, high-resolution mass spectrometry (+/-0.0002 amu), and agreement with a relative retention time index, and native standards. We found that when kreteks were smoked according to standardized machine smoke parameters as specified by the International Standards Organization, all 33 clove brands contained levels of eugenol ranging from 2,490 to 37,900 microg/cigarette (microg/cig). Anethole was detected in smoke from 13 brands at levels of 22.8-1,030 microg/cig, and coumarin was detected in 19 brands at levels ranging from 9.2 to 215 microg/cig. These detected levels are significantly higher than the levels found in commercial cigarette brands available in the United States.

Separation of 20 coumarin derivatives using the capillary electrophoresis method optimized by a series of Doehlert experimental designs.

PubMed

Woźniakiewicz, Michał; Gładysz, Marta; Nowak, Paweł M; Kędzior, Justyna; Kościelniak, Paweł

2017-05-15

The aim of this study was to develop the first CE-based method enabling separation of 20 structurally similar coumarin derivatives. To facilitate method optimization a series of three consequent Doehlert experimental designs with the response surface methodology was employed, using number of peaks and the adjusted time of analysis as the selected responses. Initially, three variables were examined: buffer pH, ionic strength and temperature (No. 1 Doehlert design). The optimal conditions provided only partial separation, on that account, several buffer additives were examined at the next step: organic cosolvents and cyclodextrin (No. 2 Doehlert design). The optimal cyclodextrin type was also selected experimentally. The most promising results were obtained for the buffers fortified with methanol, acetonitrile and heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin. Since these additives may potentially affect acid-base equilibrium and ionization state of analytes, the third Doehlert design (No. 3) was used to reconcile concentration of these additives with optimal pH. Ultimately, the total separation of all 20 compounds was achieved using the borate buffer at basic pH 9.5 in the presence of 10mM cyclodextrin, 9% (v/v) acetonitrile and 36% (v/v) methanol. Identity of all compounds was confirmed using the in-lab build UV-VIS spectra library. The developed method succeeded in identification of coumarin derivatives in three real samples. It demonstrates a huge resolving power of CE assisted by addition of cyclodextrins and organic cosolvents. Our unique optimization approach, based on the three Doehlert designs, seems to be prospective for future applications of this technique. Copyright © 2017 Elsevier B.V. All rights reserved.

Antimicrobial activity of Ulopterol isolated from Toddalia asiatica (L.) Lam.: a traditional medicinal plant.

PubMed

Karunai Raj, M; Balachandran, C; Duraipandiyan, V; Agastian, P; Ignacimuthu, S

2012-03-06

The leaves of Toddalia asiatica (L.) Lam. (Rutaceae) are widely used in folk medicine in India to treat various ailments like cough, malaria, indigestion, influenza lung diseases and rheumatism, fever, stomach ailments, cholera and diarrhea. In our earlier communication we have reported the antimicrobial study on the various extracts of the leaves and the isolation and identification of Flindersine, a quinolone alkaloid as the major active principle. In the present study, we report the antibacterial and antifungal activities of Ulopterol, a coumarin isolated as another major active antimicrobial principle. The leaves were successively extracted with hexane, chloroform, ethyl acetate, methanol and water. The extracts were studied for their antimicrobial activity against selected bacteria and fungi by using disc-diffusion method. The ethyl acetate extract which was found to possess highest antimicrobial activity was subjected to activity guided fractionation by column chromatography over silica gel. This resulted in the isolation of the coumarin, Ulopetrol, an active principle besides Flindersine which was reported by us earlier. The structure of the compound was elucidated using physical and spectroscopic data. Flindersine and Ulopterol were quantified by HPLC. Ulopterol showed activity against the bacteria viz. Staphylococcus epidermidis, Enterobacter aerogenes, Shigella flexneri, Klebsiella pneumoniae (ESBL-3967), Escherichia coli (ESBL-3984) and fungi viz. Aspergillus flavus, Candida krusei and Botrytis cinerea. Quantification by HPLC showed the content of Flindersine and Ulopterol to be 0.361% and 0.266% respectively on dry weight basis of the leaves. Ethyl acetate extract (successive extraction) contained Ulopterol, a coumarin, besides Flindersine, a quinolone alkaloid, as a major active principle in the antimicrobial studies. This is the first report of the antimicrobial activity of Ulopterol and also its first report from the plant. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Rapid and quantitative detection of zoonotic influenza A virus infection utilizing coumarin-derived dendrimer-based fluorescent immunochromatographic strip test (FICT).

PubMed

Yeo, Seon-Ju; Huong, Dinh Thi; Hong, Nguyen Ngoc; Li, Chun-Ying; Choi, Kyunghan; Yu, Kyoungsik; Choi, Du-Young; Chong, Chom-Kyu; Choi, Hak Soo; Mallik, Shyam Kumar; Kim, Hak Sung; Sung, Haan Woo; Park, Hyun

2014-01-01

Great efforts have been made to develop robust signal-generating fluorescence materials which will help in improving the rapid diagnostic test (RDT) in terms of sensitivity and quantification. In this study, we developed coumarin-derived dendrimer-based fluorescent immunochromatographic strip test (FICT) assay with enhanced sensitivity as a quantitative diagnostic tool in typical RDT environments. The accuracy of the proposed FICT was compared with that of dot blot immunoassay techniques and conventional RDTs. Through conjugation of coumarin-derived dendrimers with latex beads, fluorescent emission covering broad output spectral ranges was obtained which provided a distinct advantage of easy discrimination of the fluorescent emission of the latex beads with a simple insertion of a long-pass optical filter away from the excitation wavelength. The newly developed FICT assay was able to detect 100 ng/10 μL of influenza A nucleoprotein (NP) antigen within 5 minutes, which corresponded to 2.5-fold higher sensitivity than that of the dot blot immunoassay or conventional RDTs. Moreover, the FICT assay was confirmed to detect at least four avian influenza A subtypes (H5N3, H7N1, H7N7, and H9N2). On applying the FICT to the clinical swab samples infected with respiratory viruses, our FICT assay was confirmed to differentiate influenza H1N1 infection from other respiratory viral diseases. These data demonstrate that the proposed FICT assay is able to detect zoonotic influenza A viruses with a high sensitivity, and it enables the quantitation of the infection intensity by providing the numerical diagnostic values; thus demonstrating enhanced detectability of influenza A viruses.

PEG-coumarin nanoaggregates as π-π stacking derived small molecule lipophile containing self-assemblies for anti-tumour drug delivery.

PubMed

Behl, Gautam; Kumar, Parveen; Sikka, Manisha; Fitzhenry, Laurence; Chhikara, Aruna

2018-03-01

Polymeric self-assemblies formed by non-covalent interactions such as hydrophobic interactions, hydrogen bonding, π-π stacking, host-guest and electrostatic interactions have been utilised widely and exhibit controlled release of encapsulated drug. Beside carrier-carrier interactions, small molecule amphiphiles exhibiting carrier-drug interactions have recently been an area of interest for cancer drug delivery, as most of the hydrophobic anti-tumour drugs are aromatic and exhibit π-π conjugated structure. In the present study PEG-coumarin (PC) conjugates forming self-assembled nanoaggregates were synthesised with PEG (polyethylene glycol) as hydrophilic block and coumarin as small molecule lipophilic segment. Curcumin (CUR) as model conjugated aromatic drug was loaded in to the nanoaggregates via dual hydrophobic and π-π stacking interactions. The interactions between the conjugates and CUR, drug release profile and in vitro anti-tumour efficacy were investigated in detail. CUR-loaded nanoaggregate self-assembly was driven by π-π interactions and a maximum loading level of about 18 wt.% (~60 % encapsulation efficiency) was achieved. The average hydrodynamic diameter (D av ) was in the range of 120-160 nm and a spherical morphology was observed by transmission electron microscopy (TEM). A sustained release of CUR was observed for 90 h. Cytotoxicity evaluation of CUR-loaded nanoaggregates on pancreatic cancer cell lines indicated higher efficacy, IC 50 ~11 and ~15 μM as compared to free CUR, IC 50 ~14 and ~20 μM on human pancreatic carcinoma (MIA PaCa-2) and human pancreatic duct epithelioid carcinoma (PANC-1) cell lines respectively. PC conjugates provided a new strategy of fabricating nanoparticles for drug delivery and may form the basis for the development of advanced biomaterials in near future.

A coumarin-specific prenyltransferase catalyzes the crucial biosynthetic reaction for furanocoumarin formation in parsley.

PubMed

Karamat, Fazeelat; Olry, Alexandre; Munakata, Ryosuke; Koeduka, Takao; Sugiyama, Akifumi; Paris, Cedric; Hehn, Alain; Bourgaud, Frédéric; Yazaki, Kazufumi

2014-02-01

Furanocoumarins constitute a sub-family of coumarin compounds with important defense properties against pathogens and insects, as well as allelopathic functions in plants. Furanocoumarins are divided into two sub-groups according to the alignment of the furan ring with the lactone structure: linear psoralen and angular angelicin derivatives. Determination of furanocoumarin type is based on the prenylation position of the common precursor of all furanocoumarins, umbelliferone, at C6 or C8, which gives rise to the psoralen or angelicin derivatives, respectively. Here, we identified a membrane-bound prenyltransferase PcPT from parsley (Petroselinum crispum), and characterized the properties of the gene product. PcPT expression in various parsley tissues is increased by UV irradiation, with a concomitant increase in furanocoumarin production. This enzyme has strict substrate specificity towards umbelliferone and dimethylallyl diphosphate, and a strong preference for the C6 position of the prenylated product (demethylsuberosin), leading to linear furanocoumarins. The C8-prenylated derivative (osthenol) is also formed, but to a much lesser extent. The PcPT protein is targeted to the plastids in planta. Introduction of this PcPT into the coumarin-producing plant Ruta graveolens showed increased consumption of endogenous umbelliferone. Expression of PcPT and a 4-coumaroyl CoA 2'-hydroxylase gene in Nicotiana benthamiana, which does not produce furanocoumarins, resulted in formation of demethylsuberosin, indicating that furanocoumarin production may be reconstructed by a metabolic engineering approach. The results demonstrate that a single prenyltransferase, such as PcPT, opens the pathway to linear furanocoumarins in parsley, but may also catalyze the synthesis of osthenol, the first intermediate committed to the angular furanocoumarin pathway, in other plants. © 2013 The Authors The Plant Journal © 2013 John Wiley & Sons Ltd.

Molecular Docking and Pharmacological Investigations of Rivastigmine-Fluoxetine and Coumarin-Tacrine hybrids against Acetyl Choline Esterase.

PubMed

Babitha, Pallikkara Pulikkal; Sahila, Mohammed Marunnan; Bandaru, Srinivas; Nayarisseri, Anuraj; Sureshkumar, Sivanpillai

2015-01-01

The present AChE inhibitors have been successful in the treatment of Alzheimer׳s Diseases however suffers serious side effects. Therefore in this view, the present study was sought to identify compounds with appreciable pharmacological profile targeting AChE. Analogue of Rivastigmine and Fluoxetine hybrid synthesized by Toda et al, 2003 (dataset1), and Coumarin-Tacrine hybrids synthesized by Qi Sun et al (dataset2) formed the test compounds for the present pharmacological evaluation. p-cholorophenyl substituted Rivastigmine and Fluoxetine hybrid compound (26d) from dataset 1 and -OCH3 substitute Coumarin-Tacrine hybrids (1h) from dataset 2 demonstrated superior pharmacological profile. 26 d showed superior pharmacological profile comparison to the entire compounds in either dataset owing to its better electrostatic interactions and hydrogen bonding patterns. In order to identify still better compound with pharmacological profile than 26 d and 1h, virtual screening was performed. The best docked compound (PubCId: PubCid: 68874404) showed better affinity than its parent 26 d, however showed poor ADME profile and AMES toxicity. CHEMBL2391475 (PubCid: 71699632) similar to 1h had reduced affinity in comparison to its parent compound 1h. From, our extensive analysis involving binding affinity analysis, ADMET properties predictions and pharmacophoric mappings, we report p-cholorophenyl substituted rivastigmine and fluoxetine hybrid (26d) to be a potential candidate for AcHE inhibition which in addition can overcome narrow therapeutic window of present AChE inhibitors in clinical treatment of Alzheimer׳s disease. AD - Alzheimer׳s Disease, AChE - Acetyl Choline Estarase, OPLS - Optimized Potentials for Liquid Simulations, PDB - Protein Data Bank.

Exclusive photorelease of signalling lipids at the plasma membrane.

PubMed

Nadler, André; Yushchenko, Dmytro A; Müller, Rainer; Stein, Frank; Feng, Suihan; Mulle, Christophe; Carta, Mario; Schultz, Carsten

2015-12-21

Photoactivation of caged biomolecules has become a powerful approach to study cellular signalling events. Here we report a method for anchoring and uncaging biomolecules exclusively at the outer leaflet of the plasma membrane by employing a photocleavable, sulfonated coumarin derivative. The novel caging group allows quantifying the reaction progress and efficiency of uncaging reactions in a live-cell microscopy setup, thereby greatly improving the control of uncaging experiments. We synthesized arachidonic acid derivatives bearing the new negatively charged or a neutral, membrane-permeant coumarin caging group to locally induce signalling either at the plasma membrane or on internal membranes in β-cells and brain slices derived from C57B1/6 mice. Uncaging at the plasma membrane triggers a strong enhancement of calcium oscillations in β-cells and a pronounced potentiation of synaptic transmission while uncaging inside cells blocks calcium oscillations in β-cells and causes a more transient effect on neuronal transmission, respectively. The precise subcellular site of arachidonic acid release is therefore crucial for signalling outcome in two independent systems.

Development of an in Silico Model of DPPH• Free Radical Scavenging Capacity: Prediction of Antioxidant Activity of Coumarin Type Compounds.

PubMed

Goya Jorge, Elizabeth; Rayar, Anita Maria; Barigye, Stephen J; Jorge Rodríguez, María Elisa; Sylla-Iyarreta Veitía, Maité

2016-06-07

A quantitative structure-activity relationship (QSAR) study of the 2,2-diphenyl-l-picrylhydrazyl (DPPH•) radical scavenging ability of 1373 chemical compounds, using DRAGON molecular descriptors (MD) and the neural network technique, a technique based on the multilayer multilayer perceptron (MLP), was developed. The built model demonstrated a satisfactory performance for the training ( R 2 = 0.713 ) and test set ( Q ext 2 = 0.654 ) , respectively. To gain greater insight on the relevance of the MD contained in the MLP model, sensitivity and principal component analyses were performed. Moreover, structural and mechanistic interpretation was carried out to comprehend the relationship of the variables in the model with the modeled property. The constructed MLP model was employed to predict the radical scavenging ability for a group of coumarin-type compounds. Finally, in order to validate the model's predictions, an in vitro assay for one of the compounds (4-hydroxycoumarin) was performed, showing a satisfactory proximity between the experimental and predicted pIC50 values.

Photo-triggered release in polyamide nanosized capsules

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

Marturano, V.; Ambrogi, V.; Cerruti, P.

2014-05-15

In this work, nanosized capsules based on a lightly cross-linked polyamide containing azobenzene moieties in the main chain were synthesized by miniemulsion interfacial polymerization. The obtained nanocapsules were loaded either with toluene or with the fluorescent probe coumarin-6 as a core. Diameters of the nanocapsules were in the 100-900 nm range, depending on the selected emulsion conditions. The morphology and shape of the samples were observed by TEM and SEM while the emulsion droplets and nanocapsules size was measured by DLS. Under continuous UV irradiation the polymer underwent E-Z photoisomerization allowing the release of the encapsulated material. Variation in diametermore » of the nanocapsules with the time of UV irradiation was detected through DLS analysis. 10-30% growth was observed, depending on the sample. The kinetics of release of coumarin-6 was followed by spectrofluorimetry in ethanol. In absence of irradiation, the fluorescence intensity appeared to be constant over time, while it increased when the sample was irradiated with 360 nm UV light.« less

Inhibition of Mild Steel Corrosion in Hydrochloric Acid Solution by New Coumarin

PubMed Central

Kadhum, Abdul Amir H.; Mohamad, Abu Bakar; Hammed, Leiqaa A.; Al-Amiery, Ahmed A.; San, Ng Hooi; Musa, Ahmed Y.

2014-01-01

A new coumarin derivative, N,N′-((2E,2′E)-2,2′-(1,4-phenylenebis(methanylylidene))bis(hydrazinecarbonothioyl))bis(2-oxo-2H-chromene-3-carboxamide) PMBH, was synthesized and its chemical structure was elucidated and confirmed using spectroscopic techniques (Infrared spectroscopy IR, Proton nuclear magnetic resonance, 1H-NMR and carbon-13 nuclear magnetic resonance 13C-NMR). The corrosion inhibition effect of PMBH on mild steel in 1.0 M HCl was investigated using corrosion potential (ECORR), potentiodynamic polarization, electrochemical impedance spectroscopy (EIS), and electrochemical frequency modulation (EFM) measurements. The obtained results indicated that PMBH has promising inhibitive effects on the corrosion of mild steel in 1.0 M HCl across all of the conditions examined. Scanning electron microscopy (SEM) was used to investigate the morphology of the mild steel before and after immersion in 1.0 M HCl solution containing 0.5 mM of PMBH. Surface analysis revealed improvement of corrosion resistance in presence of PMBH. PMID:28788680

Comparative pharmacokinetic study of the main components of cortex fraxini after oral administration in normal and hyperuricemic rats.

PubMed

Wang, Yinan; Zhao, Min; Ye, Hao; Shao, Yizhen; Yu, Yongbo; Wang, Miao; Zhao, Chunjie

2017-08-01

Cortex Fraxini is an important traditional Chinese herbal medicine used for the treatment of gout and hyperuricemia. An efficient and rapid ultra-performance liquid chromatography mass spectrometry method was developed and validated for simultaneous quantitation of six coumarins (aesculin, fraxin, aesculetin, fraxetin, sopoletin and 7-hydroxycoumarin) in normal and hyperuricemic rats plasma after oral administration of Cortex Fraxini. The method could successfully be applied for pharmacokinetics studies. The pharmacokinetic behavior of six coumarins in normal and hyperuricemia rats plasma was determined. Results showed that, for some of analytes, the pharmacokinetic parameters (AUC 0-t , AUC 0-∞ , C max , T max and CL) were significantly different between normal and hyperuricemic rats. The different pharmacokinetic parameters might result from renal impairment or a change of metabolic enzymes in the pathological state. The pharmacokinetic study in pathological state could provide more useful information to guide the clinical use of traditional Chinese herbal medicine. Copyright © 2017 John Wiley & Sons, Ltd.

Synthesis, characterization, antimicrobial and antitumor reactivity of new palladium(II) complexes with methionine and tryptophane coumarine derivatives

NASA Astrophysics Data System (ADS)

Stojković, Danijela Lj; Jevtić, Verica V.; Vuković, Nenad; Vukić, Milena; Čanović, Petar; Zarić, Milan M.; Mišić, Milena M.; Radovanović, Dragče M.; Baskić, Dejan; Trifunović, Srećko R.

2018-04-01

In reaction of 3-acetyl-4-hydroxy coumarine with methionine methyl ester hydrochloride and tryptophane methyl ester hydrochloride the corresponding enamine ligands were obtained. Palladium (II) complexes were prepared in reaction of potassium-tetrachloridopalladate (II) and corresponding enamine. All compounds were characterized by microanalysis, infrared, 1H and 13C NMR spectroscopy. In vitro antitumor activity of the mentioned ligands and corresponding palladium (II) complexes, as well as me-Gly and me-Val ligands and [Pd (me-Gly)]Cl and [Pd (me-Val)2] complexes was determined by MTT assay against two leukemia cell lines (JVM-13 and MOLT-4) and against primary leukemic cells isolated from chronic lymphocytic leukemia (CLL) patients. Antimicrobial activity of the tested compound was evaluated by determining the minimum inhibitory concentration (MIC) and minimum microbicidal concentration (MMC) against three reference bacterial strains: E. faecalis, P. aeruginosa, S. aureus and one clinical isolate of yeast: Candida spp.

Altering intra- to inter-molecular hydrogen bonding by dimethylsulfoxide: A TDDFT study of charge transfer for coumarin 343

NASA Astrophysics Data System (ADS)

Liu, Xiaochun; Yin, Hang; Li, Hui; Shi, Ying

2017-04-01

DFT and TDDFT methods were carried out to investigate the influences of intramolecular and intermolecular hydrogen bonding on excited state charge transfer for coumarin 343 (C343). Intramolecular hydrogen bonding is formed between carboxylic acid group and carbonyl group in C343 monomer. However, in dimethylsulfoxide (DMSO) solution, DMSO 'opens up' the intramolecular hydrogen bonding and forms solute-solvent intermolecular hydrogen bonded C343-DMSO complex. Analysis of frontier molecular orbitals reveals that intramolecular charge transfer (ICT) occurs in the first excited state both for C343 monomer and complex. The results of optimized geometric structures indicate that the intramolecular hydrogen bonding interaction is strengthened while the intermolecular hydrogen bonding is weakened in excited state, which is confirmed again by monitoring the shifts of characteristic peaks of infrared spectra. We demonstrated that DMSO solvent can not only break the intramolecular hydrogen bonding to form intermolecular hydrogen bonding with C343 but also alter the mechanism of excited state hydrogen bonding strengthening.

Inhibition of Mild Steel Corrosion in Hydrochloric Acid Solution by New Coumarin.

PubMed

Kadhum, Abdul Amir H; Mohamad, Abu Bakar; Hammed, Leiqaa A; Al-Amiery, Ahmed A; San, Ng Hooi; Musa, Ahmed Y

2014-06-05

A new coumarin derivative, N , N '-((2E,2'E)-2,2'-(1,4-phenylenebis (methanylylidene))bis(hydrazinecarbonothioyl))bis(2-oxo-2H-chromene-3-carboxamide) PMBH, was synthesized and its chemical structure was elucidated and confirmed using spectroscopic techniques (Infrared spectroscopy IR, Proton nuclear magnetic resonance, 1 H-NMR and carbon-13 nuclear magnetic resonance 13 C-NMR). The corrosion inhibition effect of PMBH on mild steel in 1.0 M HCl was investigated using corrosion potential ( E CORR ), potentiodynamic polarization, electrochemical impedance spectroscopy (EIS), and electrochemical frequency modulation (EFM) measurements. The obtained results indicated that PMBH has promising inhibitive effects on the corrosion of mild steel in 1.0 M HCl across all of the conditions examined. Scanning electron microscopy (SEM) was used to investigate the morphology of the mild steel before and after immersion in 1.0 M HCl solution containing 0.5 mM of PMBH. Surface analysis revealed improvement of corrosion resistance in presence of PMBH.

A coumarin-derived Cu2 +-fluorescent chemosensor and its direct application in aqueous media

NASA Astrophysics Data System (ADS)

Mergu, Naveen; Kim, Myeongjin; Son, Young-A.

2018-01-01

A novel coumarin-based receptor bearing a benzohydrazide (FCBH) was developed as a fluorescent chemosensor with high selectivity toward Cu2 +. The sensor was successfully applied to the monitoring of Cu2 + in aqueous solution. After the addition of Cu2 + to FCBH, the color of the solution changed from greenish-yellow to red, and the absorption band at 457 nm red-shifted to 517 nm. The fluorescent green color of FCBH disappeared and the fluorescence emission was completely quenched in the presence of Cu2 +. Upon the addition of Cu2 +, deprotonation of FCBH occurred, and a 1:1 metal-ligand complex formed. DFT theoretical investigation was carried out to understand the behavior of the sensing probe toward Cu2 +. Additionally, the quenched fluorescence of the FCBH-Cu2 + complex was restored upon the addition of CN- ions. The possible sensing mechanism of FCBH toward Cu2 + was derived from experimental and theoretical examinations.

Structure-based design, synthesis and biological evaluation of β-glucuronidase inhibitors

NASA Astrophysics Data System (ADS)

Khan, Khalid M.; Ambreen, Nida; Taha, Muhammad; Halim, Sobia A.; Zaheer-ul-Haq; Naureen, Shagufta; Rasheed, Saima; Perveen, Shahnaz; Ali, Sajjad; Choudhary, Mohammad Iqbal

2014-05-01

Using structure-based virtual screening approach, a coumarin derivative ( 1) was identified as β-glucuronidase inhibitor. A focused library of coumarin derivatives was synthesized by eco-benign version of chemical reaction, and all synthetic compounds were characterized by using spectroscopy. These compounds were found to be inhibitor of β-glucuronidase with IC50 values in a micromolar range. All synthetic compounds exhibited interesting inhibitory activity against β-glucuronidase, however, their potency varied substantially from IC50 = 9.9-352.6 µM. Of twenty-one compounds, four exhibited a better inhibitory profile than the initial hit 1. Interestingly, compounds 1e, 1k, 1n and 1p exhibited more potency than the standard inhibitor with IC50 values 34.2, 21.4, 11.7, and 9.9 µM, respectively. We further studied their dose responses and also checked our results by using detergent Triton ×-100. We found that our results are true and not affected by detergent.

Structure-based design, synthesis and biological evaluation of β-glucuronidase inhibitors.

PubMed

Khan, Khalid M; Ambreen, Nida; Taha, Muhammad; Halim, Sobia A; Zaheer-ul-Haq; Naureen, Shagufta; Rasheed, Saima; Perveen, Shahnaz; Ali, Sajjad; Choudhary, Mohammad Iqbal

2014-05-01

Using structure-based virtual screening approach, a coumarin derivative (1) was identified as β-glucuronidase inhibitor. A focused library of coumarin derivatives was synthesized by eco-benign version of chemical reaction, and all synthetic compounds were characterized by using spectroscopy. These compounds were found to be inhibitor of β-glucuronidase with IC50 values in a micromolar range. All synthetic compounds exhibited interesting inhibitory activity against β-glucuronidase, however, their potency varied substantially from IC50 = 9.9-352.6 µM. Of twenty-one compounds, four exhibited a better inhibitory profile than the initial hit 1. Interestingly, compounds 1e, 1k, 1n and 1p exhibited more potency than the standard inhibitor with IC50 values 34.2, 21.4, 11.7, and 9.9 µM, respectively. We further studied their dose responses and also checked our results by using detergent Triton ×-100. We found that our results are true and not affected by detergent.

Spectroscopic, Homo-Lumo and NLO studies of tetra fluoro phthalate doped Coumarin crystals using DFT method

NASA Astrophysics Data System (ADS)

Latha, B.; Kumaresan, P.; Nithiyanantham, S.; Sampathkumar, K.

2017-08-01

In the present examination, a methodical study has been done on the development of unadulterated and Coumarin doped Tetrafluoro Phthalate precious stones. Powder X-beam diffraction studies were done and the cross section parameters were computed by minimum square technique in pure and doped crystals. FT-IR, UV-Vis, Thermal, Micro-hardness and Dielectric studies were additionally done for the pure and doped crystals. The tentatively watched FT-IR and FT-Raman groups were allotted to various ordinary methods of the atom. The steadiness and charge delocalization of the particle were likewise concentrations were done by characteristic security orbital (NBO) examination. The HOMO-LUMO energies depict the charge exchange happens inside the particle. Atomic electrostatic potential has been broken down the electronic properties such as excitation energies, oscillator quality, wavelengths and HOMO-LUMO energies were acquired by time-subordinate DFT (TD-DFT) approach. The SHG of pure and doped TFP stones were examined through Nd:YAG Q-exchanged laser.

Quantification of bioactive compounds in pulps and by-products of tropical fruits from Brazil.

PubMed

Ribeiro da Silva, Larissa Morais; Teixeira de Figueiredo, Evania Altina; Silva Ricardo, Nagila Maria Pontes; Pinto Vieira, Icaro Gusmao; Wilane de Figueiredo, Raimundo; Brasil, Isabella Montenegro; Gomes, Carmen L

2014-01-15

This study aimed to quantify the levels of resveratrol, coumarin, and other bioactives in pulps and by-products of twelve tropical fruits from Brazil obtained during pulp production process. Pineapple, acerola, monbin, cashew apple, guava, soursop, papaya, mango, passion fruit, surinam cherry, sapodilla, and tamarind pulps were evaluated as well as their by-products (peel, pulp's leftovers, and seed). Total phenolic, anthocyanins, yellow flavonoids, β-carotene and lycopene levels were also determined. Resveratrol was identified in guava and surinam cherry by-products and coumarin in passion fruit, guava and surinam cherry by-products and mango pulp. These fruit pulp and by-products could be considered a new natural source of both compounds. Overall, fruit by-products presented higher (P<0.05) bioactive content than their respective fruit pulps. This study provides novel information about tropical fruits and their by-products bioactive composition, which is essential for the understanding of their nutraceutical potential and future application in the food industry. Published by Elsevier Ltd.

Green, unexpected synthesis of bis-coumarin derivatives as potent anti-bacterial and anti-inflammatory agents.

PubMed

Chougala, Bahubali M; Samundeeswari, S; Holiyachi, Megharaja; Naik, Nirmala S; Shastri, Lokesh A; Dodamani, Suneel; Jalalpure, Sunil; Dixit, Sheshagiri R; Joshi, Shrinivas D; Sunagar, Vinay A

2018-01-01

A green and efficient protocol has been developed and a series of coumarin based pyrano[3,2-c]chromene derivatives (2) have been synthesized using multi-component reaction (MCR) approach. Unexpected 3-coumarinyl-3-pyrazolylpropanoic acids (3) and C 4 -C 4 chromenes (5) have been isolated instead of expected product 4 by the reaction of compound (2) in formic acid at 90 °C for about 4-5 h and at 130 °C for about 8-10 h respectively. Further, C 4 -C 4 chromenes (5) formation was confirmed by intramolecular cyclization of compounds (3). These compounds were screened for their biological activities and most of them exhibited promising antibacterial activity. The anti-inflammatory assay was evaluated against HRBC membrane stabilization method and the compounds exhibit excellent anti-inflammatory activity. Molecular docking study has been performed for all the synthesized compounds with Klebsiella pneumoni aeacetolactate synthase and results obtained are quite promising. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

A Benzothiadiazole Primes Parsley Cells for Augmented Elicitation of Defense Responses

PubMed Central

Katz, Vera A.; Thulke, Oliver U.; Conrath, Uwe

1998-01-01

Systemic acquired resistance is an important component of the disease-resistance arsenal of plants, and is associated with an enhanced potency for activating local defense responses upon pathogen attack. Here we demonstrate that pretreatment with benzothiadiazole (BTH), a synthetic activator of acquired resistance in plants, augmented the sensitivity for low-dose elicitation of coumarin phytoalexin secretion by cultured parsley (Petroselinum crispum L.) cells. Enhanced coumarin secretion was associated with potentiated activation of genes encoding Phe ammonia-lyase (PAL). The augmentation of PAL gene induction was proportional to the length of pretreatment with BTH, indicating time-dependent priming of the cells. In contrast to the PAL genes, those for anionic peroxidase were directly induced by BTH in the absence of elicitor, thus confirming a dual role for BTH in the activation of plant defenses. Strikingly, the ability of various chemicals to enhance plant disease resistance correlated with their capability to potentiate parsley PAL gene elicitation, emphasizing an important role for defense response potentiation in acquired plant disease resistance. PMID:9701589

Phenolic chemical composition of Petroselinum crispum extract and its effect on haemostasis.

PubMed

Chaves, Douglas S A; Frattani, Flávia S; Assafim, Mariane; de Almeida, Ana Paula; de Zingali, Russolina B; Costa, Sônia S

2011-07-01

From the aqueous extract (Pc) of Petroselinum crispum (Mill) flat leaves specimens were isolated and identified the flavonoids apigenin (1), apigenin-7-O-glucoside or cosmosiin (2), apigenin-7-O-apiosyl-(1 --> 2)-O-glucoside or apiin (3) and the coumarin 2",3"-dihydroxyfuranocoumarin or oxypeucedanin hydrate (4). The inhibitory activity toward clotting formation and platelet aggregation was assessed for Pc flavonoids (1) and (2), and the coumarin (4). Pc showed no inhibition on clotting activity when compared with the control. On the other hand, a strong antiplatelet aggregation activity was observed for Pc (IC50 = 1.81 mg/mL), apigenin (IC50 = 0.036 mg/mL) and cosmosiin (IC50 = 0.18 mg/mL). In all cases ADP was used as inductor of platelet aggregation. Our results showed that Pc, apigenin and cosmosiin interfere on haemostasis inhibiting platelet aggregation. To the best of our knowledge this is the first report for the cosmosiin antiplatelet aggregation in vitro activity.

Computational Study on New Natural Compound Inhibitors of Pyruvate Dehydrogenase Kinases

PubMed Central

Zhou, Xiaoli; Yu, Shanshan; Su, Jing; Sun, Liankun

2016-01-01

Pyruvate dehydrogenase kinases (PDKs) are key enzymes in glucose metabolism, negatively regulating pyruvate dehyrogenase complex (PDC) activity through phosphorylation. Inhibiting PDKs could upregulate PDC activity and drive cells into more aerobic metabolism. Therefore, PDKs are potential targets for metabolism related diseases, such as cancers and diabetes. In this study, a series of computer-aided virtual screening techniques were utilized to discover potential inhibitors of PDKs. Structure-based screening using Libdock was carried out following by ADME (adsorption, distribution, metabolism, excretion) and toxicity prediction. Molecular docking was used to analyze the binding mechanism between these compounds and PDKs. Molecular dynamic simulation was utilized to confirm the stability of potential compound binding. From the computational results, two novel natural coumarins compounds (ZINC12296427 and ZINC12389251) from the ZINC database were found binding to PDKs with favorable interaction energy and predicted to be non-toxic. Our study provide valuable information of PDK-coumarins binding mechanisms in PDK inhibitor-based drug discovery. PMID:26959013

Computational Study on New Natural Compound Inhibitors of Pyruvate Dehydrogenase Kinases.

PubMed

Zhou, Xiaoli; Yu, Shanshan; Su, Jing; Sun, Liankun

2016-03-04

Pyruvate dehydrogenase kinases (PDKs) are key enzymes in glucose metabolism, negatively regulating pyruvate dehyrogenase complex (PDC) activity through phosphorylation. Inhibiting PDKs could upregulate PDC activity and drive cells into more aerobic metabolism. Therefore, PDKs are potential targets for metabolism related diseases, such as cancers and diabetes. In this study, a series of computer-aided virtual screening techniques were utilized to discover potential inhibitors of PDKs. Structure-based screening using Libdock was carried out following by ADME (adsorption, distribution, metabolism, excretion) and toxicity prediction. Molecular docking was used to analyze the binding mechanism between these compounds and PDKs. Molecular dynamic simulation was utilized to confirm the stability of potential compound binding. From the computational results, two novel natural coumarins compounds (ZINC12296427 and ZINC12389251) from the ZINC database were found binding to PDKs with favorable interaction energy and predicted to be non-toxic. Our study provide valuable information of PDK-coumarins binding mechanisms in PDK inhibitor-based drug discovery.

Laser performance of Coumarin 540A dye molecules in polymeric host media with different viscosities: From liquid solution to solid polymer matrix

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

Costela, A.; Garcia-Moreno, I.; Barroso, J.

1998-01-01

Photophysical parameters and lasing properties of Coumarin 540A dye molecules are studied in solutions of increasing viscosity, from liquid solutions in 1,4-dioxane to solid solutions in poly(methyl methacrylate). The fluorescence quantum yield and lasing efficiencies decrease as the viscosity of the solution increases, reflecting the strong influence of the rigidity of the medium on the radiative processes. The photodegradation mechanisms acting on the fluorophores are analyzed by following the dependence of laser induced fluorescence and laser output on the number of pump laser pulses. The fluorescence redistribution after pattern photobleaching technique is used, and Fick{close_quote}s second law is applied tomore » study the diffusion of dye molecules in the highly viscous polymer solutions. The diffusion coefficients of the dye molecules as a function of the increased viscosity of the medium are determined. {copyright} {ital 1998 American Institute of Physics.}« less

From evidence based medicine to mechanism based medicine. Reviewing the role of pharmacogenetics.

PubMed

Wilffert, Bob; Swen, Jesse; Mulder, Hans; Touw, Daan; Maitland-Van der Zee, Anke-Hilse; Deneer, Vera

2013-06-01

The translation of evidence based medicine to a specific patient presents a considerable challenge. We present by means of the examples nortriptyline, tramadol, clopidogrel, coumarins, abacavir and antipsychotics the discrepancy between available pharmacogenetic information and its implementation in daily clinical practice. Literature review. A mechanism based approach may be helpful to personalize medicine for the individual patient to which pharmacogenetics may contribute significantly. The lack of consistency in what we accept in bioequivalence and in pharmacogenetics of drug metabolising enzymes is discussed and illustrated with the example of nortriptyline. The impact of pharmacogenetics on examples like tramadol, clopidogrel, coumarins and abacavir is described. Also the present status of the polymorphisms of 5-HT2A and C receptors in antipsychotic-induced weight gain is presented as a pharmacodynamic example with until now a greater distance to clinical implementation. The contribution of pharmacogenetics to tailor-made pharmacotherapy, which especially might be of value for patients deviating from the average, has not yet reached the position it seems to deserve.

Discovery of a Novel Class of Survival Motor Neuron 2 Splicing Modifiers for the Treatment of Spinal Muscular Atrophy.

PubMed

Pinard, Emmanuel; Green, Luke; Reutlinger, Michael; Weetall, Marla; Naryshkin, Nikolai A; Baird, John; Chen, Karen S; Paushkin, Sergey V; Metzger, Friedrich; Ratni, Hasane

2017-05-25

Spinal muscular atrophy (SMA) is caused by mutation or deletion of the survival motor neuron 1 (SMN1) gene, resulting in low levels of functional SMN protein. We have reported recently the identification of small molecules (coumarins, iso-coumarins and pyrido-pyrimidinones) that modify the alternative splicing of SMN2, a paralogous gene to SMN1, restoring the survival motor neuron (SMN) protein level in mouse models of SMA. Herein, we report our efforts to identify a novel chemotype as one strategy to potentially circumvent safety concerns from earlier derivatives such as in vitro phototoxicity and in vitro mutagenicity associated with compounds 1 and 2 or the in vivo retinal findings observed in a long-term chronic tox study with 3 at high exposures only. Optimized representative compounds modify the alternative splicing of SMN2, increase the production of full length SMN2 mRNA, and therefore levels of full length SMN protein upon oral administration in two mouse models of SMA.

Buffalo calves intoxicated with Ageratum houstonianum mill

USDA-ARS?s Scientific Manuscript database

Ageratum houstonianum Mill, a noxious weed has been reported to contain pyrrolizidine alkaloids, saponins, triterpens and coumarin. It is an invasive weed that is commonly found in the pasturelands of tropical and subtropical regions. The objectives of this work were to verify the toxicity of A. ho...

Laboratory evaluation of plant-derived antifeedants against the pine weevil Hylobius abietis (Coleoptera: Curculionidae)

Treesearch

Kier D. Klepzig; Fredrik Schlyter

1999-01-01

The authors assayed 12 plant-derived and 1 insect-produced allelochemicals-verbenone, borneol, bornyl acetate, carvone, cucurbitacin, myrcene, limonin, 4-allyanisole, a- pinene, ß-pinene, limonene, and coumarin-for inhibition of feeding by the pine weevil Hylobius abietis L...

Synthetic substrates for enzyme analysis

DOEpatents

Bissell, E.R.; Mitchell, A.R.; Pearson, K.W.; Smith, R.E.

1983-06-14

Synthetic substrates are provided which may be represented as A-D. The A moiety includes an amino acid, polypeptide, or derivative. The D moiety includes 7-amino coumarin derivatives having an electron withdrawing substituent group at the 3 position carbon or fused between the 3 and 4 position carbons. No Drawings

Sagebrush identification, ecology, and palatability relative to sage-grouse

Treesearch

Roger Rosentreter

2005-01-01

Basic identification keys and comparison tables for 23 low and big sagebrush (Artemisia) taxa are presented. Differences in sagebrush ecology, soil temperature regimes, geographic range, palatability, mineralogy, and chemistry are discussed. Coumarin, a chemical produced in the glands of some Artemisia species, causes UV-light fluorescence of the...

[Reviews on antiviral activity of chemical constituents from plants].

PubMed

Yang, Xian-Feng; Wang, Yu-Li; Xu, Wei-Ren

2008-01-01

This paper reviewed the progress in researches on antiviral activity of chemical constituents from plants in recent years, the antiviral activity and mechanism of action of flavonoids, alkaloids, terpenoids, coumarins and polysaccharoses were sammarszed, provided new leading compound for antivirus new drugs from the plares in prospect.

Synthetic substrates for enzyme analysis

DOEpatents

Bissell, Eugene R.; Mitchell, Alexander R.; Pearson, Karen W.; Smith, Robert E.

1983-01-01

Synthetic substrates are provided which may be represented as A-D. The A moiety thereof includes an amino acid, polypeptide, or derivative thereof. The D moiety thereof includes 7-amino coumarin derivatives having an electron withdrawing substituent group at the 3 position carbon or fused between the 3 and 4 position carbons.

Minor furanocoumarins and coumarins in grapefruit peel oil as inhibitors of human cytochrome P450 3A4

USDA-ARS?s Scientific Manuscript database

A novel cyclic acetal of 6',7'-dihydroxy-7-geranyloxycoumarin (marmin) and two novel cyclic acetals of 6',7'-dihydroxybergamottin were isolated from nonvolatile residues of grapefruit peel oil. Other known compounds, marmin, 7-geranyloxycoumarin, bergamottin, and 6',7'-dihydroxybergamottin were also...

Anti-Leishmania Activity of Osthole

PubMed Central

Kermani, Elaheh Kordzadeh; Sajjadi, Seyed Ebrahim; Hejazi, Seyed Hossein; Arjmand, Reza; Saberi, Sedigheh; Eskandarian, Abbas Ali

2016-01-01

Background: Treatment of cutaneous leishmaniasis (CL) is occasionally highly resistant to pentavalent antimonials, the gold standard in pharmacotherapy of CL. Since there is no effective vaccine, the discovery of natural antileishmanial products as complementary therapeutic agents could be used to improve the current regimens. Objective: In this study in vitro and in vivo antileishmanial activities of osthole, a natural coumarin known to possess antibacterial and parasiticidal activities are evaluated. Materials and Methods: Leishmania major infected J774.A1 macrophages were treated with increasing concentrations of osthole. CL lesions of BALB/c mice were treated topically with 0.2% osthole. Results: Osthole exhibited dose-dependent leishmanicidal activity against intracellular amastigotes with IC50 value of 14.95 μg/ml. Treatment of CL lesions in BALB/c mice with osthole significantly declined lesion progression compared to untreated mice (P < 0.05), however did not result in recovery. Conclusion: Osthole demonstrated remarkable leishmanicidal activity in vitro. Higher concentrations of osthole may demonstrate the therapeutic property in vivo. SUMMARY In vitro and in vivo antileishmanial activities of osthole, a pernylated coumarin extracted from Prangos asperula Boiss., are studied against Leishmania major. PMID:27114685

Effects of esculin and esculetin on the survival of Escherichia coli O157 in human faecal slurries, continuous-flow simulations of the rumen and colon and in calves.

PubMed

Duncan, Sylvia H; Leitch, E Carol McWilliam; Stanley, Karen N; Richardson, Anthony J; Laven, Richard A; Flint, Harry J; Stewart, Colin S

2004-05-01

The human pathogen Escherichia coli O157:H7 is thought to be spread by direct or indirect contact with infected animal or human faeces. The present study investigated the effects of the plant coumarin esculin and its aglycone esculetin on the survival of a strain of E. coli O157 under gut conditions. The addition of these compounds to human faecal slurries and in vitro continuous-flow fermenter models simulating conditions in the human colon and rumen caused marked decreases in the survival of an introduced strain of E. coli O157. When four calves were experimentally infected with E. coli O157 and fed esculin, the pathogen was detected in five of twenty-eight (18 %) of faecal samples examined post-inoculation, compared with thirteen of thirty-five (37 %) of faecal samples examined from five control calves not fed esculin. Coumarin compounds that occur naturally in dietary plants or when supplemented in the diet probably inhibit the survival of E. coli O157 in the gut.

[Inhibitory effects of 11 coumarin compounds against growth of human bladder carcinoma cell line E-J in vitro].

PubMed

Yang, Xiu-wei; Xu, Bo; Ran, Fu-xiang; Wang, Rui-qing; Wu, Jun; Cui, Jing-rong

2007-01-01

To screen antitumor active compounds, drug-like or leading compounds from Chinese traditional and herbal drugs. Eleven coumarin compounds isolated from the Chinese traditional and herbal drugs were studied for their antitumor activities in vitro by determining the inhibition rates against growth of human bladder carcinoma cell line E-J. It showed that umbelliferone, scoparone, demethylfuropinarine, isopimpinellin, forbesoside, columbianadin, decursin and glycycoumarin inhibited the growth of human bladder carcinoma cell line E-J in vitro and their activities showed a concentration-effect relationship. The inhibitory effects of forbesoside, columbianadin, decursin and umbelliferone, with IC50 values of 7.50x10(-7), 2.30x10(-6), 6.00x10(-6) and 1.30x10(-6) mol/L, respectively, were stronger than those of the other tested compounds. However, xanthotoxin, esculin and sphondin did not inhibit the growth of human bladder carcinoma cell line E-J in this assay condition. These findings indicate that forbesoside, columbianadin, esculin, decursin and umbelliferone would be effective or regarded as potent drug-like or leading compounds against human bladder carcinoma.

A Thiazole Coumarin (TC) Turn-On Fluorescence Probe for AT-Base Pair Detection and Multipurpose Applications in Different Biological Systems

NASA Astrophysics Data System (ADS)

Narayanaswamy, Nagarjun; Kumar, Manoj; Das, Sadhan; Sharma, Rahul; Samanta, Pralok K.; Pati, Swapan K.; Dhar, Suman K.; Kundu, Tapas K.; Govindaraju, T.

2014-09-01

Sequence-specific recognition of DNA by small turn-on fluorescence probes is a promising tool for bioimaging, bioanalytical and biomedical applications. Here, the authors report a novel cell-permeable and red fluorescent hemicyanine-based thiazole coumarin (TC) probe for DNA recognition, nuclear staining and cell cycle analysis. TC exhibited strong fluorescence enhancement in the presence of DNA containing AT-base pairs, but did not fluoresce with GC sequences, single-stranded DNA, RNA and proteins. The fluorescence staining of HeLa S3 and HEK 293 cells by TC followed by DNase and RNase digestion studies depicted the selective staining of DNA in the nucleus over the cytoplasmic region. Fluorescence-activated cell sorting (FACS) analysis by flow cytometry demonstrated the potential application of TC in cell cycle analysis in HEK 293 cells. Metaphase chromosome and malaria parasite DNA imaging studies further confirmed the in vivo diagnostic and therapeutic applications of probe TC. Probe TC may find multiple applications in fluorescence spectroscopy, diagnostics, bioimaging and molecular and cell biology.

Cytotoxic constituents of Soymida febrifuga from Myanmar.

PubMed

Awale, Suresh; Miyamoto, Tatsuya; Linn, Thein Zaw; Li, Feng; Win, Nwet Nwet; Tezuka, Yasuhiro; Esumi, Hiroyasu; Kadota, Shigetoshi

2009-09-01

The 70% ethanol extract of Soymida febrifuga was found to kill PANC-1 human pancreatic cancer cells preferentially under nutrition-deprived conditions at a concentration of 10 microg/mL. Phytochemical investigation led to the isolation of 27 compounds including four new compounds [(3R)-6,4'-dihydroxy-8-methoxyhomoisoflavan (1), (2R)-7,4'-dihydroxy-5-methoxy-8-methylflavan (2), 7-hydroxy-6-methoxy-3-(4'-hydroxybenzyl)coumarin (3), and 6-hydroxy-7-methoxy-3-(4'-hydroxybenzyl)coumarin (4)]. 2',4'-Dihydroxychalcone (8) displayed the most potent preferential cytotoxicity (PC(50) 19.0 microM) against PANC-1 cells. In addition, the cytotoxic activity against colon 26-L5 carcinoma (colon 26-L5), B16-BL6 melanoma (B16-BL6), lung A549 adenocarcinoma (A549), cervix HeLa adenocarcinoma (HeLa), and HT-1080 fibrosarcoma (HT-1080) cell lines and their structure-activity relationship are discussed. The cytotoxic activity of 4'-hydroxy-3,5-dimethoxystilbene (6) against colon 26-L5 (IC(50) 2.96 microM) was found to be stronger than the positive control, doxorubicin, at IC(50) 3.12 microM.

A straightforward method to determine flavouring substances in food by GC-MS.

PubMed

Lopez, Patricia; van Sisseren, Maarten; De Marco, Stefania; Jekel, Ad; de Nijs, Monique; Mol, Hans G J

2015-05-01

A straightforward GC-MS method was developed to determine the occurrence of fourteen flavouring compounds in food. It was successfully validated for four generic types of food (liquids, semi-solids, dry solids and fatty solids) in terms of limit of quantification, linearity, selectivity, matrix effects, recovery (53-120%) and repeatability (3-22%). The method was applied to a survey of 61 Dutch food products. The survey was designed to cover all the food commodities for which the EU Regulation 1334/2008 set maximum permitted levels. All samples were compliant with EU legislation. However, the levels of coumarin (0.6-63 mg/kg) may result in an exposure that, in case of children, would exceed the tolerable daily intake (TDI) of 0.1mg/kg bw/day. In addition to coumarin, estragole, methyl-eugenol, (R)-(+)-pulegone and thujone were EU-regulated substances detected in thirty-one of the products. The non-EU regulated alkenylbenzenes, trans-anethole and myristicin, were commonly present in beverages and in herbs-containing products. Copyright © 2014 Elsevier Ltd. All rights reserved.

Structure-Activity Relationship Analysis of 3-phenylcoumarin-Based Monoamine Oxidase B Inhibitors

NASA Astrophysics Data System (ADS)

Rauhamäki, Sanna; Postila, Pekka A.; Niinivehmas, Sanna; Kortet, Sami; Schildt, Emmi; Pasanen, Mira; Manivannan, Elangovan; Ahinko, Mira; Koskimies, Pasi; Nyberg, Niina; Huuskonen, Pasi; Multamäki, Elina; Pasanen, Markku; Juvonen, Risto O.; Raunio, Hannu; Huuskonen, Juhani; Pentikäinen, Olli T.

2018-03-01

Monoamine oxidase B (MAO-B) catalyzes deamination of monoamines such as neurotransmitters dopamine and norepinephrine. Accordingly, small-molecule MAO-B inhibitors potentially alleviate the symptoms of dopamine-linked neuropathologies such as depression or Parkinson’s disease. Coumarin with a functionalized 3-phenyl ring system is a promising scaffold for building potent MAO-B inhibitors. Here, a vast set of 3-phenylcoumarin derivatives was designed using virtual combinatorial chemistry or rationally de novo and synthesized using microwave chemistry. The derivatives inhibited the MAO-B at 100 nM - 1 µM. The IC50 value of the most potent derivative 1 was 56 nM. A docking-based structure-activity relationship analysis summarizes the atom-level determinants of the MAO-B inhibition by the derivatives. Finally, the cross-reactivity of the derivatives was tested against monoamine oxidase A and a specific subset of enzymes linked to estradiol metabolism, known to have coumarin-based inhibitors. Overall, the results indicate that the 3-phenylcoumarins, especially derivative 1, present unique pharmacological features worth considering in future drug development.

Anti-Inflammatory and Neuroprotective Constituents from the Peels of Citrus grandis.

PubMed

Kuo, Ping-Chung; Liao, Yu-Ren; Hung, Hsin-Yi; Chuang, Chia-Wei; Hwang, Tsong-Long; Huang, Shiow-Chyn; Shiao, Young-Ji; Kuo, Daih-Huang; Wu, Tian-Shung

2017-06-09

A series of chromatographic separations performed on the ethanol extracts of the peels of Citrus grandis has led to the characterization of forty compounds, including seventeen coumarins, eight flavonoids, two triterpenoids, four benzenoids, two steroids, one lignan, one amide, and five other compounds, respectively. The chemical structures of the purified constituents were identified on the basis of spectroscopic elucidation, including 1D- and 2D-NMR, UV, IR, and mass spectrometric analysis. Most of the isolated compounds were examined for their inhibition of superoxide anion generation and elastase release by human neutrophils. Among the isolates, isomeranzin ( 3 ), 17,18-dihydroxybergamottin ( 12 ), epoxybergamottin ( 13 ), rhoifolin ( 19 ), vitexicarpin ( 22 ) and 4-hydroxybenzaldehyde ( 29 ) displayed the most significant inhibition of superoxide anion generation and elastase release with IC 50 values ranged from 0.54 to 7.57 μM, and 0.43 to 4.33 μM, respectively. In addition, 7-hydroxy-8-(2'-hydroxy-3'-methylbut-3'-enyl)coumarin ( 8 ) and 17,18-dihydroxybergamottin ( 12 ) also exhibited the protection of neurons against A-mediated neurotoxicity at 50 μM.

Isolation and Identification of Mosquito (Aedes aegypti) Biting-Deterrent Compounds from the Native American Ethnobotanical Remedy Plant Hierochloë odorata (Sweetgrass).

PubMed

Cantrell, Charles L; Jones, A Maxwell P; Ali, Abbas

2016-11-09

Hierochloë odorata (L.) P. Beauv. (Poaceae), commonly known as sweetgrass, has documented use as an insect repellent by the Flatheads of Montana and Blackfoot of Alberta. Both the Flatheads of Montana and Blackfoot of Alberta would use braided plant material in a sachet in clothing or burn them from one end as incense, air/clothing freshener, and insect repellent. This study evaluated the insect-repellent properties of this plant using an in vitro mosquito Aedes aegypti feeding bioassay-directed approach to identify the compound(s) responsible for the observed activities. Evaluation of crude extracts produced from H. odorata revealed that the hydrodistillate had the highest level of mosquito biting deterrence. Fractionation of this extract, followed by re-evaluation for mosquito biting deterrence, produced many active fractions, which were evaluated by spectroscopic techniques and determined to contain phytol, coumarin, and 2-methoxy-4-vinylphenol. Phytol and coumarin were both determined to be responsible for the Ae. aegypti biting deterrency. Scientific evidence reported here validates its traditional use as a biting-insect deterrent.

A Thiazole Coumarin (TC) Turn-On Fluorescence Probe for AT-Base Pair Detection and Multipurpose Applications in Different Biological Systems

PubMed Central

Narayanaswamy, Nagarjun; Kumar, Manoj; Das, Sadhan; Sharma, Rahul; Samanta, Pralok K.; Pati, Swapan K.; Dhar, Suman K.; Kundu, Tapas K.; Govindaraju, T.

2014-01-01

Sequence-specific recognition of DNA by small turn-on fluorescence probes is a promising tool for bioimaging, bioanalytical and biomedical applications. Here, the authors report a novel cell-permeable and red fluorescent hemicyanine-based thiazole coumarin (TC) probe for DNA recognition, nuclear staining and cell cycle analysis. TC exhibited strong fluorescence enhancement in the presence of DNA containing AT-base pairs, but did not fluoresce with GC sequences, single-stranded DNA, RNA and proteins. The fluorescence staining of HeLa S3 and HEK 293 cells by TC followed by DNase and RNase digestion studies depicted the selective staining of DNA in the nucleus over the cytoplasmic region. Fluorescence-activated cell sorting (FACS) analysis by flow cytometry demonstrated the potential application of TC in cell cycle analysis in HEK 293 cells. Metaphase chromosome and malaria parasite DNA imaging studies further confirmed the in vivo diagnostic and therapeutic applications of probe TC. Probe TC may find multiple applications in fluorescence spectroscopy, diagnostics, bioimaging and molecular and cell biology. PMID:25252596

Design, synthesis and evaluation of coumarin-pargyline hybrids as novel dual inhibitors of monoamine oxidases and amyloid-β aggregation for the treatment of Alzheimer's disease.

PubMed

Yang, Hua-Li; Cai, Pei; Liu, Qiao-Hong; Yang, Xue-Lian; Li, Fan; Wang, Jin; Wu, Jia-Jia; Wang, Xiao-Bing; Kong, Ling-Yi

2017-09-29

A series of coumarin-pargyline hybrids (4a-x) have been designed, synthesized and evaluated as novel dual inhibitors of Alzheimer's disease (AD). Most of the compounds exhibited a potent ability to inhibit amyloid-β (Aβ) aggregation and monoamine oxidases. In particular, compound 4x exhibited remarkable inhibitory activities against monoamine oxidases (IC 50 , 0.027 ± 0.004 μM for MAO-B; 3.275 ± 0.040 μM for MAO-A) and Aβ 1-42 aggregation (54.0 ± 1.1%, 25 μM). Moreover, compound 4x showed low toxicity according to in vitro cell toxicity test. The results of the parallel artificial membrane permeability assay for blood-brain barrier indicated that compound 4x would be potent to cross the blood-brain barrier. Collectively, these findings demonstrate that compound 4x was an effective and promising candidate for AD therapy. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Photoinduced electron transfer in a room temperature ionic liquid 1-butyl-3-methylimidazolium octyl sulfate micelle: a temperature dependent study.

PubMed

Sarkar, Souravi; Mandal, Sarthak; Pramanik, Rajib; Ghatak, Chiranjib; Rao, Vishal Govind; Sarkar, Nilmoni

2011-05-19

The effect of temperature on the dynamics of photoinduced electron transfer (PET) between different coumarin dyes and N,N-dimethyl aniline in a room temperature ionic liquid 1-butyl-3-methylimidazolium octyl sulfate ([C(4)mim][C(8)SO(4)]) micelle have been investigated using steady-state and time-resolved fluorescence quenching measurements at four different temperatures: 208, 298, 308, and 318 K. The quenching rates (k(q)(TR)) of the PET process in this micellar system are found to be lower than the PET rate in sodium dodecyl sulfate and Triton-X 100 micelle and almost comparable to the dodecyl trimethyl ammonium bromide and cetyl trimethyl ammonium bromide micelle due to larger donor–acceptor separation in the micellar phase. The temperature dependent PET rates are well correlated with the Arrhenius type of correlation for all the coumarin dyes. Marcus type of inversion in PET rates has been observed at relatively lower exergonicity, and the correlation plots gradually move upward with the increase of temperature. © 2011 American Chemical Society

Multi-state nonadiabatic deactivation mechanism of coumarin revealed by ab initio on-the-fly trajectory surface hopping dynamic simulation.

PubMed

Gan, Yanzhen; Yue, Ling; Guo, Xugeng; Zhu, Chaoyuan; Cao, Zexing

2017-05-17

An on-the-fly trajectory surface hopping dynamic simulation has been performed for revealing the multi-state nonadiabatic deactivation mechanism of coumarin. The mechanism involves three adiabatic excited states, S 3 (ππ*L b ), S 2 (nπ*, ππ*L a ) and S 1 (ππ*L a , nπ*), and the ground state S 0 at the four state-averaged complete active space self-consistent field, SA4-CASSCF(12,10)/6-31G* level of theory. Upon photoexcitation to the third excited state S 3 (ππ*L b ) in the Franck-Condon region, 80% sampling trajectories decay to the dark S 2 (nπ*) state within an average of 5 fs via the conical intersection S 3 (ππ*L b )/S 2 (nπ*), while 20% decay to the S 2 (ππ*L a ) state within an average of 11 fs via the conical intersection S 3 (ππ*L b )/S 2 (ππ*L a ). Then, sampling trajectories via S 2 (nπ*)/S 1 (ππ*L a ) continue with ultrafast decay processes to give a final distribution of quantum yields as follows: 42% stay on the dark S 1 (nπ*) state, 43.3% go back to the ground S 0 state, 12% undergo a ring-opening reaction to the Z-form S 0 (Z) state, and 2.7% go to the E-form S 0 (E) state. The lifetimes of the excited states are estimated as follows: the S 3 state is about 12 fs on average, the S 2 state is about 80 fs, and the S 1 state has a fast component of about 160 fs and a slow component of 15 ps. The simulated ultrafast radiationless deactivation pathways of photoexcited coumarin immediately interpret the experimentally observed weak fluorescence emission.

Vitamin K antagonists and pregnancy outcome. A multi-centre prospective study.

PubMed

Schaefer, Christof; Hannemann, Doreen; Meister, Reinhard; Eléfant, Elisabeth; Paulus, Wolfgang; Vial, Thierry; Reuvers, Minke; Robert-Gnansia, Elisabeth; Arnon, Judy; De Santis, Marco; Clementi, Maurizio; Rodriguez-Pinilla, Elvira; Dolivo, Alla; Merlob, Paul

2006-06-01

Vitamin K antagonists (VKA) are known to act as teratogens; however, there is still uncertainty about the relative risk for birth defects and the most sensitive period. In a multi-centre (n = 12), observational, prospective study we compared 666 pregnant women exposed to phenprocoumon (n = 280), acenocoumarol (n = 226), fluindione (n = 99), warfarin (n = 63) and phenindione (n = 2) to a non-exposed control group (n = 1,094). Data were collected by institutes collaborating in the European Network of Teratology Information Services (ENTIS) during individual risk counselling between 1988 and 2004. Main outcome measures were coumarin embryopathy and other birth defects, miscarriage rate, birth-weight, and prematurity. The rate of major birth defects after 1st trimester exposure was significantly increased (OR 3.86, 95% CI 1.86-8.00). However, there were only two coumarin embryopathies (0.6%; both phenprocoumon). Prematurity was more frequent (16.0% vs. 7.6%, OR 2.61, 95% CI 1.76-3.86), mean gestational age at delivery (37.9 vs.39.4, p<0.001), and mean birth weight of term infants (3,166 g vs. 3,411 g; p < 0.001) were lower compared to the controls. Using the methodology of survival analysis, miscarriage rate reached 42% vs. 14% (hazard ratio 3.36; 95% CI 2.28-4.93). In conclusion, use of VKA during pregnancy increases the risk of structural defects and other adverse pregnancy outcomes. The risk for coumarin embryopathy is, however, very small, in particular when therapy during the 1(st) trimester did not take place later than week 8 after the 1(st) day of the last menstrual period. Therefore, elective termination of a wanted pregnancy is not recommended if (inadvertent) exposure took place in early pregnancy. Close follow-up by the obstetrician including level II ultrasound should be recommended in any case of VKA exposure during pregnancy.

Influence of electrolytes on the microenvironment of F127 triblock copolymer micelles: a solvation and rotational dynamics study of coumarin dyes.

PubMed

Kumbhakar, Manoj; Ganguly, Rajib

2007-04-19

Dynamic Stokes' shift and fluorescence anisotropy measurements of coumarin 153 (C153) and coumarin 151 (C151) as fluorescence probes have been carried out to understand the influence of electrolytes (NaCl and LiCl) on the hydration behavior of aqueous (ethylene oxide)100-(propylene oxide)70-(ethylene oxide)100 (EO100-PO70-EO100, F127) block copolymer micelles. A small blue shift in the fluorescence spectra of C153 has been observed in presence of electrolytes due to the dehydration of the oxyethylene chains in the PEO-PPO region, although fluorescence spectra of C151 remain unaltered. The close vicinity of bulk water for C151 probably negates the effect of dehydration in the PEO region. Fluorescence anisotropy measurements indicate a gradual increase in microviscosity with electrolyte concentrations. The partial collapse of copolymer blocks in the presence of electrolytes has been suggested as a reason for the increase in microviscosity along with the strong hydration of ions in the corona region. The interplay between the ion hydration and the mechanically trapped water content, and specific interaction of ions, such as complexation of Li+ ions with the copolymer block, is found to control solvation dynamics in the corona region. In addition to that, it has been established that Na+ ions reside deep into the corona region whereas Li+ ions prefer to reside closer to the surface. Owing to its higher lyotropicity, LiCl influences the corona hydration to a greater extent than NaCl and sets in micelle-micelle interaction above the 2 M LiCl concentration, as reflected in the saturation of solvation time constants. The formation of larger clusters of F127 micelles above 2 M LiCl has been confirmed by dynamic light scattering measurements; however, such cluster formation is not evident with NaCl.

Interaction of cruciferin-based nanoparticles with Caco-2 cells and Caco-2/HT29-MTX co-cultures.

PubMed

Akbari, Ali; Lavasanifar, Afsaneh; Wu, Jianping

2017-12-01

The objective of this work was to assess the potential of Cruciferin/Calcium (Cru/Ca) and Cruciferin/Chitosan (Cru/Cs) nanoparticles for oral drug delivery. For this purpose, Cru/Ca and Cru/Cs nanoparticles were developed through cold gelation of Cruciferin, a major canola protein, and in interaction with calcium and chitosan, respectively. The extent and rate of particle uptake in Caco-2 cells and Caco-2/HT29 co-culture was then evaluated by fluorescence spectroscopy as well as flow cytometry. Through pre-incubation of Caco-2 cell monolayer with specific endocytosis inhibitors, the mechanism of cell uptake was investigated. Our results showed that the uptake of negatively-charged Cru/Ca particles to be ∼3 times higher than positively-charged Cru/Cs ones by Caco-2 cells. Presence of mucus secreted by HT29 cells in their co-culture with Caco-2 had negligible influence on the uptake and transport of both particles. In contrast to Cru/Ca particles which were dissociated in the simulated gastrointestinal conditions, digestion of Cru/Cs particles resulted in 6- and 2-fold increase in the cellular uptake and transport of encapsulated coumarin in the latter particles, respectively. While the presence of mucus in Caco-2/HT29 co-culture caused 40-50% decrease of cellular uptake and transport for coumarin encapsulated in digested Cru/Cs particles, it had no significant effect on the cell uptake and transport of coumarin associated with Cru/Ca particles after digestion. Energy-dependent mechanisms were the dominant mechanism for uptake of both undigested and digested particles. Therefore, in Caco-2/HT29 co-culture which closely simulated intestinal epithelial cells, undigested Cru/Ca and Cru/Cs particles had the ability to penetrate mucus layers, while digested Cru/Cs particles showed mucoadhesive property, and digested Cru/Ca particles were dissociated. Our results points to a potential for cruciferin based nanoparticles for oral drug delivery. The long-term objective of this research is to investigate the potential of edible and safe biopolymer in enhanced oral delivery of drugs and/or vaccines. Here, we investigated the potential application of nanoparticles based on a protein extracted from Canola seeds, i.e., cruciferin, for oral delivery of a model small molecule, i.e., coumarin, through cells representing gastrointestinal epithelium, Caco-2 and Caco-2/HT29 cell monolayer. This study was completed for intact cruciferin nanoparticles and cruciferin coated chitosan nanoparticles, before and after digestion with gastric or intestine simulating fluids. This comparison was useful to understand the fate the cruciferin based particles in digestive mucosal tissues and their potential mucoadhesive and/or mucus-penetrating property. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

The HPLC-Fluorescence Detection of Coumarins in ‘Hamlin’ Sweet Orange and ‘Marsh’ Grapefruit Leaf Cankers

USDA-ARS?s Scientific Manuscript database

Canker is a devastating disease for the citrus fresh fruit market and is caused by the pathogenic bacterium Xanthomonas citri var. citri (Xcc). Infection occurs by bacterial penetration through physical damage of leaves, peel and stems, and also by bacterial entry through the stomates of these photo...

Palladium-catalyzed, pyrrolidine-mediated arylmethylation of ketones and aldehydes with coumarinyl(methyl) acetates.

PubMed

Cattopadhyay, Kalicharan; Recio, Antonio; Tunge, Jon A

2012-09-14

We report the palladium-catalyzed, pyrrolidine-mediated α-benzylation of enamines generated from aldehydes and ketones. The method allows for direct coupling of medicinally relevant coumarin moieties with aldehydes and ketones in good yield under mild conditions. The reaction is believed to proceed via a Pd-π-benzyl complex generated from (coumarinyl)methyl acetates.

Solvent Effects on Emission Yield and Lifetime for Coumarin Laser Dyes. Requirements for a Rotatory Decay Mechanism.

DTIC Science & Technology

1983-10-31

spectral shifts and sizeable solvent iso- tope effects have been frequently observed for solvent exciplexes , e in contrast to our findings. The results also...49. Chandross, E. A.; "The Exciplex " Gordon, M.; Ware, W. R. (ed.) 4 Academic Press, Inc.: New York; 1975; p 187. SO. a. Beecroft, R. A.; Davidson, R

A TEMPO-conjugated fluorescent probe for monitoring mitochondrial redox reactions.

PubMed

Hirosawa, Shota; Arai, Satoshi; Takeoka, Shinji

2012-05-18

We report a mitochondrial targeted redox probe (MitoRP) that comprises a nitroxide radical (TEMPO) moiety and coumarin 343. Using isolated mitochondria in the presence/absence of substrates and inhibitors of oxidative phosphorylation, we demonstrated that MitoRP is a useful probe to monitor the electron flow associated with complex I. This journal is © The Royal Society of Chemistry 2012

Synthesis of (3-Methoxycarbonyl)coumarin in an Ionic Liquid: An Advanced Undergraduate Project for Green Chemistry

ERIC Educational Resources Information Center

Verdía, Pedro; Santamarta, Francisco; Tojo, Emilia

2017-01-01

An experiment for an undergraduate organic chemistry class based on the application of an ionic liquid as solvent and catalyst of an organic reaction is reported. The whole experiment requires three 3-h lab sessions. First, students prepare the ionic liquid dimethylimidazolium methylsulfate, which is then used as a recyclable catalyst/reaction…

Palladium-catalyzed, pyrrolidine-mediated arylmethylation of ketones and aldehydes with coumarinyl(methyl) acetates†

PubMed Central

Cattopadhyay, Kalicharan; Recio, Antonio; Tunge, Jon A.

2012-01-01

We report the palladium-catalyzed, pyrrolidine-mediated α-benzylation of enamines generated from aldehydes and ketones. The method allows for direct coupling of medicinally relevant coumarin moieties with aldehydes and ketones in good yield under mild conditions. The reaction is believed to proceed via a Pd-π-benzyl complex generated from (coumarinyl)methyl acetates. PMID:22832549

Smart, Sustainable, and Ecofriendly Chemical Design of Fully Bio-Based Thermally Stable Thermosets Based on Benzoxazine Chemistry.

PubMed

Froimowicz, Pablo; R Arza, Carlos; Han, Lu; Ishida, Hatsuo

2016-08-09

A smart synthetic chemical design incorporating furfurylamine, a natural renewable amine, into a partially bio-based coumarin-containing benzoxazine is presented. The versatility of the synthetic approach is shown to be flexible and robust enough to be successful under more ecofriendly reaction conditions by replacing toluene with ethanol as the reaction solvent and even under solventless conditions. The chemical structure of this coumarin-furfurylamine-containing benzoxazine is characterized by FTIR, (1) H NMR spectroscopy and two-dimensional (1) H-(1) H nuclear Overhauser effect spectroscopy (2D (1) H-(1) H NOESY). The thermal properties of the resin toward polymerization are characterized by differential scanning calorimetry (DSC) and the thermal stability of the resulting polymers by thermogravimetric analysis (TGA). The results reveal that the furanic moiety induces a co-operative activating effect, thus lowering the polymerization temperature and also contributes to a better thermal stability of the resulting polymers. These results, in addition to those of natural renewable benzoxazine resins reviewed herein, highlight the positive and beneficial implication of designing novel bio-based polybenzoxazine and possibly other thermosets with desirable and competitive properties. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Selective and “turn-off” fluorimetric detection of mercury(II) based on coumarinyldithiolane and coumarinyldithiane in aqueous solution

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

Guo, Yuan, E-mail: guoyuan@nwu.edu.cn; Institut de Chimie Organique et Analytique, Université d’Orléans, 45067 Orléans Cedex 2; An, Jing

2015-03-15

Graphical abstract: Visual fluorescence emission of probe 3a. - Highlights: • Five novel coumarin-based fluorescent probes were developed. • A reasonable reaction mechanism was proposed and verified. • All the probes showed excellent optical properties. - Abstract: In this work, five novel coumarin-based fluorescent probes for mercury ions were developed. The recognition of mercury ions was performed via the mercury(II)-promoted desulfurization of the probes and a reasonable reaction mechanism was proposed and verified by thin layer chromatography (TLC), {sup 1}H nuclear magnetic resonance ({sup 1}H NMR) and fluorescence intensity measurements. All the probes showed excellent optical properties and exclusively distinguishmore » mercury ions from various metal ions in aqueous solutions at pH 7.4. The linear response of the fluorescence emission intensity for all the probes to the concentration of mercury ions was obtained over a wide range of 0.06–1.5 μM (0.06–0.9 μM for probe 3e). In addition, the biological toxicity and the confocal fluorescence images of probe 3a were also tested on MCF-7 cells.« less

Photoinduced smart, self-healing polymer sealant for photovoltaics.

PubMed

Banerjee, Sanjib; Tripathy, Ranjan; Cozzens, David; Nagy, Tibor; Keki, Sandor; Zsuga, Miklos; Faust, Rudolf

2015-01-28

Polyisobutylene (PIB)-based polymer networks potentially useful as smart coatings for photovoltaic devices have been developed. Low molecular weight coumarin functional triarm star PIB was synthesized via a single step SN2 reaction of bromoallyl functional triarm star PIB with 4-methylumbelliferone or umbelliferone in the presence of sodium hydride. Quantitative end functionality was confirmed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. UVA (λmax = 365 nm) induced reversible photodimerization of the coumarin moieties resulted in cross-linked elastomeric films exhibiting self-healing behavior. The extent of photodimerization/photoscission was monitored by UV-vis spectroscopy. The low oxygen (1.9 × 10(-16) mol m m(-2) s(-1) Pa(-1)) and moisture (46 × 10(-16) mol m m(-2) s(-1) Pa(-1)) permeability of the cross-linked polymer films suggest excellent barrier properties of the cross-linked polymer films. The self-healing process was studied by atomic force microscopy (AFM). For this, mechanical cuts were introduced in the cross-linked PIB films through micromachining with an AFM tip and the rate of healing induced by UV, sunlight, or both was followed by taking AFM images of the film at different time intervals during the repair process.

Synthesis, Structure-Activity Relationships (SAR) and in Silico Studies of Coumarin Derivatives with Antifungal Activity

PubMed Central

de Araújo, Rodrigo S. A.; Guerra, Felipe Q. S.; de O. Lima, Edeltrudes; de Simone, Carlos A.; Tavares, Josean F.; Scotti, Luciana; Scotti, Marcus T.; de Aquino, Thiago M.; de Moura, Ricardo O.; Mendonça, Francisco J. B.; Barbosa-Filho, José M.

2013-01-01

The increased incidence of opportunistic fungal infections, associated with greater resistance to the antifungal drugs currently in use has highlighted the need for new solutions. In this study twenty four coumarin derivatives were screened in vitro for antifungal activity against strains of Aspergillus. Some of the compounds exhibited significant antifungal activity with MICs values ranging between 16 and 32 μg/mL. The structure-activity relationships (SAR) study demonstrated that O-substitutions are essential for antifungal activity. It also showed that the presence of a short aliphatic chain and/or electron withdrawing groups (NO2 and/or acetate) favor activity. These findings were confirmed using density functional theory (DFT), when calculating the LUMO density. In Principal Component Analysis (PCA), two significant principal components (PCs) explained more than 60% of the total variance. The best Partial Least Squares Regression (PLS) model showed an r2 of 0.86 and q2cv of 0.64 corroborating the SAR observations as well as demonstrating a greater probe N1 interaction for active compounds. Descriptors generated by TIP correlogram demonstrated the importance of the molecular shape for antifungal activity. PMID:23306152

Coumarinocoumarin-Based Two-Photon Fluorescent Cysteine Biosensor for Targeting Lysosome.

PubMed

Chen, Chunyang; Zhou, Liuqing; Liu, Wei; Liu, Weisheng

2018-05-15

Coumarinocoumarin, one of the coumarin derivatives, is easy to synthesize and has rich modification sites. The large conjugate plane of coumarinocoumarin gives it a more excellent optical property than conventional coumarin, for example, the two-photon fluorescence property. So, the coumarinocoumarin-based probe (CCy) has been designed and synthesized, which is the first lysosomal targeting fluorescent biosensor for cysteine. This probe was prepared by a three-step procedure as a latent fluorescence probe to achieve high sensitivity and fluorescence turn-on response toward cysteine (Cys) over homocysteine (Hcy), glutathione (GSH), and other various natural amino acids under physiological conditions. Upon addition of Cys to the solution of CCy, remarkable enhancement on 520 nm of fluorescence spectra can be monitored. This probe was then successfully used for fluorescence imaging of Cys in mice organ tissues and HeLa cells, and quantitative determination has been achieved within a certain range, which proved the permeability of CCy. The concentration of Cys in animal serum was measured and the viability exceeded 80%, indicating that CCy can be a biocompatible and rapid probe for Cys in vivo. Simultaneously, its ability to detect Cys in lysosome has been validated by its lysosomal targeting.

Characterization of an LED based photoreactor to degrade 4-chlorophenol in an aqueous medium using coumarin (C-343) sensitized TiO2.

PubMed

Ghosh, Jyoti P; Langford, Cooper H; Achari, Gopal

2008-10-16

A detailed performance evaluation of a simple high intensity LED based photoreactor exploiting a narrow wavelength range of the LED to match the spectrum of a dye in a photocatalysis system is reported. A dye sensitized (coumarin-343, lambda max = 446 nm) TiO 2 photocatalyst was used for the degradation of 4-chlorophenol (4-CP) in an aqueous medium using the 436 nm LED based photoreactor. The LED reactor performed competitively with a conventional multilamp reactor and sunlight in the degradation of 4-CP. Light intensities entering the reaction vessel were measured by conventional ferrioxalate actinometry. The results can be fitted by approximate first order kinetic behavior in this system. Hydroxyl radicals were detected by spin trapping EPR, and effects of OH radical quenchers on kinetics suggest that the reaction is initiated by these radicals or their equivalents. LEDs operating at competitive intensities offer a number of advantages to the photochemist or the environmental engineer via long life, efficient current to light conversion, narrow bandwidth, forward directed output, and direct current power for remote operation. Matching light source spectrum to chromophore is a key.

Coumarin derivatives bearing benzoheterocycle moiety: synthesis, cholinesterase inhibitory, and docking simulation study

PubMed Central

Hirbod, Kimia; Jalili-baleh, Leili; Nadri, Hamid; ebrahimi, Seyed esmaeil Sadat; Moradi, Alireza; Pakseresht, Bahar; Foroumadi, Alireza; Shafiee, Abbas; Khoobi, Mehdi

2017-01-01

Objective(s): To investigate the efficiency of a novel series of coumarin derivatives bearing benzoheterocycle moiety as novel cholinesterase inhibitors. Materials and Methods: Different 7-hydroxycoumarin derivatives were synthesized via Pechmann or Knoevenagel condensation and conjugated to different benzoheterocycle (8-hydroxyquinoline, 2-mercaptobenzoxazole or 2-mercaptobenzimidazole) using dibromoalkanes 3a-m: Final compounds were evaluated against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) by Ellman’s method. Kinetic study of AChE inhibition and ligand-protein docking simulation were also carried out for the most potent compound 3b. Results: Some of the compounds revealed potent and selective activity against AChE. Compound 3b containing the quinoline group showed the best activity with an IC50 value of 8.80 μM against AChE. Kinetic study of AChE inhibition revealed the mixed-type inhibition of the enzyme by compound 3b. Ligand-protein docking simulation also showed that the flexibility of the hydrophobic five carbons linker allows the quinoline ring to form π-π interaction with Trp279 in the PAS. Conclusion: We suggest these synthesized compounds could become potential leads for AChE inhibition and prevention of AD symptoms. PMID:28868119

Crystal structure, spectral property, antimicrobial activity and DFT calculation of N-(coumarin-3-yl)-N‧-(2-amino-5-phenyl-1,3,4-thiadiazol-2-yl) urea

NASA Astrophysics Data System (ADS)

Zhang, Hong-Song; Zhang, Kong-Yan; Chen, Li-Chuan; Li, Yao-Xin; Chai, Lan-Qin

2017-10-01

N-(coumarin-3-yl)-N‧-(2-amino-5-phenyl-1,3,4-thiadiazol-2-yl) urea was synthesized and characterized by elemental analysis, IR, 1H NMR, 13C NMR, UV-Vis and emission spectroscopy, as well as by single-crystal X-ray diffraction. X-ray crystallographic analyses have indicated that the crystal structure consists of two dimethyl sulfoxide (DMSO) solvent molecules and the structural geometry of DMSO is a trigonal pyramid in shape. In the crystal structure, a self-assembling two-dimensional (2-D) layer supramolecular architecture is formed through intermolecular hydrogen bonds, Cdbnd O···π (thiadiazole ring) and π···π stacking interactions. The geometry of the compound has been optimized by the DFT method and the results are compared with the X-ray diffraction data. The electronic transitions and spectral features of the compound were carried out by using DFT/B3LYP method. In addition, the antimicrobial activity was also studied, and the highest occupied molecular orbital (HOMO), lowest unoccupied molecular orbital (LUMO), and HOMO-LUMO gap were also calculated.

Photophysical properties, photodegradation characteristics, and lasing action for coumarin dye C540A in polymeric media

NASA Astrophysics Data System (ADS)

Jones, Guilford, II; Huang, Zhennian; Pacheco, Dennis P., Jr.; Russell, Jeffrey A.

2004-07-01

Tunable solid-state dye lasers operating in the blue-green spectral region are attractive for a variety of applications. An important consideration in assessing the viability of this technology is the service life of the gain medium, which is presently limited by dye photodegradation. In this study, solid polymeric samples consisting of the coumarin dye C540A in modified PMMA were subjected to controlled photodegradation tests. The excitation laser was a flashlamp-pumped dye laser operating at 440 nm with a pulse duration of 1 μs. A complementary set of data was obtained for dye in solution phase for comparison purposes. Photophysical properties of C540A in water solution of polymethacrylic acid (PMAA) have been investigated with a view to assess the suitability of the sequestering polymer (PMAA) as an effective additive to facilitate use of a water medium for highly efficient blue-green dye lasers. Lasing action of C540A in aqueous PMAA has been realized using flashlamp-pumped laser system, yielding excellent laser efficiencies superior to that achieved in ethanolic solutions with the same dye. Laser characterization of dye in media included measurement of laser threshold, slope efficiency, pulse duration and output wavelength.

Pretreatment of Parsley (Petroselinum crispum L.) Suspension Cultures with Methyl Jasmonate Enhances Elicitation of Activated Oxygen Species.

PubMed Central

Kauss, H.; Jeblick, W.; Ziegler, J.; Krabler, W.

1994-01-01

Suspension-cultured cells of parsley (Petroselinum crispum L.) were used to demonstrate an influence of jasmonic acid methyl ester (JAME) on the elicitation of activated oxygen species. Preincubation of the cell cultures for 1 d with JAME greatly enhanced the subsequent induction by an elicitor preparation from cell walls of Phytophtora megasperma f. sp. glycinea (Pmg elicitor) and by the polycation chitosan. Shorter preincubation times with JAME were less efficient, and the effect was saturated at about 5 [mu]M JAME. Treatment of the crude Pmg elicitor with trypsin abolished induction of activated oxygen species, an effect similar to that seen with elicitation of coumarin secretion. These results suggest that JAME conditioned the parsley suspension cells in a time-dependent manner to become more responsive to elicitation, reminiscent of developmental effects caused by JAME in whole plants. It is interesting that pretreatment of the parsley cultures with 2,6-dichloroisonicotinic and 5-chlorosalicylic acid only slightly enhanced the elicitation of activated oxygen species, whereas these substances greatly enhanced the elicitation of coumarin secretion. Therefore, these presumed inducers of systemic acquired resistance exhibit a specificity different from JAME. PMID:12232189

Estimation of ground and excited state dipole moment of laser dyes C504T and C521T using solvatochromic shifts of absorption and fluorescence spectra.

PubMed

Basavaraja, Jana; Suresh Kumar, H M; Inamdar, S R; Wari, M N

2016-02-05

The absorption and fluorescence spectra of laser dyes: coumarin 504T (C504T) and coumarin 521T (C521T) have been recorded at room temperature in a series of non-polar and polar solvents. The spectra of these dyes showed bathochromic shift with increasing in solvent polarity indicating the involvement of π→π⁎ transition. Kamlet-Taft and Catalan solvent parameters were used to analyze the effect of solvents on C504T and C521T molecules. The study reveals that both general solute-solvent interactions and specific interactions are operative in these two systems. The ground state dipole moment was estimated using Guggenheim's method and also by quantum mechanical calculations. The solvatochromic data were used to determine the excited state dipole moment (μ(e)). It is observed that dipole moment value of excited state (μ(e)) is higher than that of the ground state in both the laser dyes indicating that these dyes are more polar in nature in the excited state than in the ground state. Copyright © 2015. Published by Elsevier B.V.

Synthesis and in vitro biological evaluation of novel coumarin derivatives containing isoxazole moieties on melanin synthesis in B16 cells and inhibition on bacteria.

PubMed

Pang, Guang Xian; Niu, Chao; Mamat, Nuramina; Aisa, Haji Akber

2017-06-15

A novel series of coumarin derivatives 6a-o, bearing isoxazole moieties were designed and synthesized. After that, they were evaluated for melanin synthesis in murine B16 cells and inhibitory effect on the growth of CA (Candida albicans), EC (Escherichia coli), SA (Staphylococcus aureus). It was found that eleven compounds (6b-f, 6j-o) showed a better activity on melanin synthesis than positive control (8-MOP). Among them, compounds 6d (242%) and 6f (390%), with nearly 1.6 and 2.6-fold potency compared with 8-MOP (149%) respectively, were recognized as the most promising candidate hits for further pharmacological study of anti-vitiligo. Seven halogen substituted compounds exhibited moderate antimicrobial activity against CA. It is interesting that 6e-f and 6l-m, which had two halogens on the benzene showed a comparable activity with Amphotericin B against CA. The evaluation of melanin synthesis in B16 cells and inhibitory effect on bacteria of above structurally diverse derivatives had also led to an outline of structure-activity relationship. Copyright © 2017 Elsevier Ltd. All rights reserved.

A coumarin based Schiff base probe for selective fluorescence detection of Al3 + and its application in live cell imaging

NASA Astrophysics Data System (ADS)

Sen, Bhaskar; Sheet, Sanjoy Kumar; Thounaojam, Romita; Jamatia, Ramen; Pal, Amarta Kumar; Aguan, Kripamoy; Khatua, Snehadrinarayan

2017-02-01

A new coumarin based Schiff base compound, CSB-1 has been synthesized to detect metal ion based on the chelation enhanced fluorescence (CHEF). The cation binding properties of CSB-1 was thoroughly examined in UV-vis and fluorescence spectroscopy. In fluorescence spectroscopy the compound showed high selectivity toward Al3 + ion and the Al3 + can be quantified in mixed aqueous buffer solution (MeOH: 0.01 M HEPES Buffer; 9:1; v/v) at pH 7.4 as well as in BSA media. The fluorescence intensity of CSB-1 was enhanced by 24 fold after addition of only five equivalents of Al3 +. The fluorescence titration of CSB-1 with Al3 + in mixed aqueous buffer afforded a binding constant, Ka = (1.06 ± 0.2) × 104 M- 1. The colour change from light yellow to colourless and the appearance of blue fluorescence, which can be observed by the naked eye, provides a real-time method for Al3 + sensing. Further the live cell imaging study indicated that the detection of intracellular Al3 + ions are also readily possible in living cell.

Design, Synthesis and In Vitro Anti-microbial Evaluation of Ethylene/ Propylene-1H-1,2,3-Triazole-4-Methylene-tethered Isatin-coumarin Hybrids.

PubMed

Jin, Xiaohong; Xu, Yan; Yang, Xuhong; Chen, Xiuling; Wu, Minghu; Guan, Jianguo; Feng, Lianshun

2017-01-01

A new class of ethylene/propylene-1H-1,2,3-triazole-4-methylene-tethered isatincoumarin hybrids 8a-j, integrating three anti-tuberculosis pharmacophores coumarin, isatin and 1,2,3- triazole was designed and synthesized. These hybrids were assessed for their in vitro anti-TB activity against MTB H37Rv and MDRTB, as well as anti-bacterial activity against Gram-positive and Gram-negative strains, and cytotoxicity in VERO cell line. The results showed that all hybrids with acceptable cytotoxicity (CC50: 64-512 µg/mL) exhibited weak to moderate anti-microbial activity. The most active hybrid 8i with MIC of 50 µg/mL against MTB H37Rv and MDR-TB, also has excellent cytotoxicity profile (CC50: 128 µg/mL). The resistance index of hybrid 8i was 1, indicating that hybrid 8i has no cross-resistance with the first-line anti-TB agent. Thus, hybrid 8i could act as a lead for further optimization. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Identification of a coumarin-based antihistamine-like small molecule as an anti-filoviral entry inhibitor.

PubMed

Cheng, Han; Schafer, Adam; Soloveva, Veronica; Gharaibeh, Dima; Kenny, Tara; Retterer, Cary; Zamani, Rouzbeh; Bavari, Sina; Peet, Norton P; Rong, Lijun

2017-09-01

Filoviruses, consisting of Ebola virus, Marburg virus and Cuevavirus, cause severe hemorrhagic fevers in humans with high mortality rates up to 90%. Currently, there is no approved vaccine or therapy available for the prevention and treatment of filovirus infection in humans. The recent 2013-2015 West African Ebola epidemic underscores the urgency to develop antiviral therapeutics against these infectious diseases. Our previous study showed that GPCR antagonists, particularly histamine receptor antagonists (antihistamines) inhibit Ebola and Marburg virus entry. In this study, we screened a library of 1220 small molecules with predicted antihistamine activity, identified multiple compounds with potent inhibitory activity against entry of both Ebola and Marburg viruses in human cancer cell lines, and confirmed their anti-Ebola activity in human primary cells. These small molecules target a late-stage of Ebola virus entry. Further structure-activity relationship studies around one compound (cp19) reveal the importance of the coumarin fused ring structure, especially the hydrophobic substituents at positions 3 and/or 4, for its antiviral activity, and this identified scaffold represents a favorable starting point for the rapid development of anti-filovirus therapeutic agents. Copyright © 2017 Elsevier B.V. All rights reserved.

Single step synthesis of strigolactone analogues from cyclic keto enols, germination stimulants for seeds of parasitic weeds.

PubMed

Mwakaboko, Alinanuswe S; Zwanenburg, Binne

2011-08-15

The single step synthesis of a newly designed series of strigolactones (SLs) from cyclic keto enols is described. The germinating activity of these SL analogues towards seeds of the parasitic weeds Striga and Orobanche spp. is reported. The first of these SL analogues are derived from the hydroxyl γ-pyrones kojic acid and maltol, the second type from hydroxyl α-pyrones, namely, 4-hydroxy-6-methyl-2H-pyran-2-one and 4-hydroxy-coumarin and the third type from 1,3-diketones, namely, 1,3-cyclohexane-dione (dimedone) and tricyclic 1,3-dione. All keto enols are coupled in a single step with the appropriate D-ring precursor in the presence of a base to give the desired SL analogues. All SL analogues are acceptably biologically active in inducing the germination of seeds of Striga hermonthica and Orobanchecernua. Most interesting are the analogues derived from 4-hydroxy coumarin and dimedone, as they have a remarkably high biological activity towards the seeds of parasitic weeds at relatively low concentrations, comparable with that of the general standard stimulant GR24. Copyright © 2011 Elsevier Ltd. All rights reserved.

Vertical Leaching of Allelochemicals Affecting Their Bioactivity and the Microbial Community of Soil.

PubMed

Xiao, Zhongxiang; Le, Chang; Xu, Zhenghao; Gu, Zhefeng; Lv, Junfei; Shamsi, Imran Haider

2017-09-13

Leaching of allelochemicals in soil is one of the fundamental processes that determines allelopathic activities but is often overlooked. In the present study, the vertical leaching of seven putative allelochemicals as well as one pesticide and one herbicide was investigated using polyvinyl chloride columns combined with a bioassay approach. The results indicated that the leachability of pretilachlor and imidacloprid were the best (Lf > 0.8), followed by vanillin and coumarin (Lf > 0.6). The leachability of daidzein, menthol, and m-tyrosine were medium (0.3 < Lf < 0.6). The lowest leachability has been observed on p-coumaric and p-hydroxybenzoic acids (Lf < 0.3). The chemicals were classified into three clusters according to the phospholipid fatty acid profile (i.e., vanillin in one cluster, coumarin and menthol in the second cluster, and the rest in the third cluster). Bioactivities of the chemicals changed dramatically. Germination of lettuce seeds was suppressed by imidacloprid and pretilachlor, and the suppression was concentration-dependent. The bioactivity of most of the allelochemicals were progressively decreased with the downward movement of chemicals. The results indicated that leaching mediated the microbial communities and the interactions of chemical-microorganism and modified the bioavailability of allelochemicals in soil.

New Coumarin Derivatives as Potent Selective COX-2 Inhibitors: Synthesis, Anti-Inflammatory, QSAR, and Molecular Modeling Studies.

PubMed

Dawood, Dina H; Batran, Rasha Z; Farghaly, Thoraya A; Khedr, Mohammed A; Abdulla, Mohamed M

2015-12-01

Two new series of coumarin derivatives incorporating thiazoline and thiazolidinone moieties were designed, synthesized, and investigated in vivo for their anti-inflammatory activities using the carrageenan-induced rat paw edema model and in vitro for their inhibitory activities against the human cyclooxygenase (COX)-1 and COX-2 isoforms. Most of the synthesized compounds demonstrated exceptionally high in vivo anti-inflammatory activity and displayed superior GI safety profiles (0-7% ulceration) as compared to indomethacin. All the bioactive compounds showed in vitro high affinity and selectivity toward the COX-2 isoenzyme, compared to the reference celecoxib with IC50 values ranging from 0.31 to 0.78 μM. The ethyl thiosemicarbazone 2b, thiazoline derivatives 3a, 3b, 5b, 6a, and 7f, and the thiazolidinone compounds 8b and 9a showed the highest in vivo and in vitro anti-inflammatory activities with remarkable COX-2 selectivity. Quantitative structure-activity relationship study (QSAR) was done and resulted in a highly predictive power R(2) (0.908). A molecular docking study revealed a relationship between the docking affinity and the biological results. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

In vivo imaging of sulfotransferases

DOEpatents

Barrio, Jorge R; Kepe, Vladimir; Small, Gary W; Satyamurthy, Nagichettiar

2013-02-12

Radiolabeled tracers for sulfotransferases (SULTs), their synthesis, and their use are provided. Included are substituted phenols, naphthols, coumarins, and flavones radiolabeled with .sup.18F, .sup.123I, .sup.124I, .sup.125I, or .sup.11C. Also provided are in vivo techniques for using these and other tracers as analytical and diagnostic tools to study sulfotransferase distribution and activity, in health and disease, and to evaluate therapeutic interventions.

A general palladium-catalyzed carbonylative synthesis of chromenones from salicylic aldehydes and benzyl chlorides.

PubMed

Wu, Xiao-Feng; Wu, Lipeng; Jackstell, Ralf; Neumann, Helfried; Beller, Matthias

2013-09-09

Cute CO! An interesting and straightforward procedure for the carbonylative synthesis of chromenones from readily available salicylic aldehydes and benzyl chlorides has been developed (see scheme; DPPP = 1,3-bis(diphenylphosphino)propane). In the presence of a palladium catalyst, various coumarins were produced in good to excellent yields. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The Sol-Gel-Xerogel Transition

DTIC Science & Technology

1993-11-01

basic pH. Bioactive sol-gel glasses obtained by a surface adsorption of trypsin to a readymade xerogel were also completley * L...presence of siloxane chains and hydrophobic methyl groups an easy film deposition on glass sheets can be obtained. Rhodamine 6G and Coumarin 4 were...Research Proposal was prepared (early 1989) have witnessed a tremendous, almost explosive, progress in the field of organically doped sol-gel glasses

New platinum (II) and palladium (II) complexes of coumarin-thiazole Schiff base with a fluorescent chemosensor properties: Synthesis, spectroscopic characterization, X-ray structure determination, in vitro anticancer activity on various human carcinoma cell lines and computational studies.

PubMed

Şahin, Ömer; Özdemir, Ümmühan Özmen; Seferoğlu, Nurgül; Genc, Zuhal Karagöz; Kaya, Kerem; Aydıner, Burcu; Tekin, Suat; Seferoğlu, Zeynel

2018-01-01

A new coumarin-thiazole based Schiff base (Ligand, L) and its Pd(II), Pt(II) complexes; ([Pd(L) 2 ] and [Pt(L) 2 ]), were synthesized and characterized using spectrophotometric techniques (NMR, IR, UV-vis, LC-MS), magnetic moment, and conductivity measurements. A single crystal X-ray analysis for only L was done. The crystals of L have monoclinic crystal system and P21/c space group. To gain insight into the structure of L and its complexes, we used density functional theory (DFT) method to optimize the molecules. The photophysical properties changes were observed after deprotonation of L with CN - via intermolecular charge transfer (ICT). Additionally, as the sensor is a colorimetric and fluorimetric cyanide probe containing active sites such as coumarin-thiazole and imine (CH=N), it showed fast color change from yellow to deep red in the visible region, and yellow fluorescence after CN - addition to the imine bond, in DMSO. The reaction mechanisms of L with CN - , F - and AcO - ions were evaluated using 1 H NMR shifts. The results showed that, the reaction of L with CN - ion was due to the deprotonation and addition mechanisms at the same time. The anti-cancer activity of L and its Pd(II) and Pt(II) complexes were evaluated in vitro using MTT assay on the human cancer lines MCF-7 (human breast adenocarcinoma), LS174T (human colon carcinoma), and LNCAP (human prostate adenocarcinoma). The anti-cancer effects of L and its complexes, on human cells, were determined by comparing the half maximal inhibitory concentration (IC 50 ) values. The activity results showed that, the Pd(II) complex of L has higher anti-tumor effect than L and its Pt(II) complex against the tested human breast adenocarcinoma (MCF-7), human prostate adenocarcinoma (LNCAP), and human colon carcinoma (LS174T) cell lines. Copyright © 2017 Elsevier B.V. All rights reserved.

Synthesis and evaluation of 7-substituted coumarin derivatives as multimodal monoamine oxidase-B and cholinesterase inhibitors for the treatment of Alzheimer's disease.

PubMed

Joubert, Jacques; Foka, Germaine B; Repsold, Benjamin P; Oliver, Douglas W; Kapp, Erika; Malan, Sarel F

2017-01-05

A series of 7-substituted coumarin derivatives were designed and synthesised to display ChE and MAO-B inhibitory activity. The compounds consisted out of a coumarin structure (MAO-B inhibitor) and benzyl-, piperidine-, N-benzylpiperidine- or p-bromo-N-benzylpiperizine moiety, resembling the N-benzylpiperidine function of donepezil (ChE inhibitor), connected via an alkyl ether linkage at the 7 position. The biological assay results indicated that all the compounds (1-25) displayed selective inhibition to hMAO-B over hMAO-A, with the benzyloxy series (1-8, 10-13) showing nano-molar hMAO-B inhibition (IC 50 : 0.5-73 nM). Limited ChE inhibitory activity was however observed for the benzyloxy series with the exception of 2 and especially 3 showing selective BuChE inhibition. From this series 3 showed the best multifunctional activity (eqBuChE IC 50  = 0.96 μM, hMAO-A IC 50  = 2.13 μM, hMAO-B IC 50  = 0.0021 μM). Within the N-benzylpiperidine (16-19) and p-bromo-N-benzylpiperizine (21-24) series the compounds in general showed moderate ChE and MAO-B inhibitory activity. Of these compounds 19 was the most potent multifunctional agent showing good eeAChE and eqBuChE inhibition (IC 50  = 9.10 μM and 5.90 μM, respectively), and relatively potent and selective hMAO-B inhibition (IC 50  = 0.30 μM, SI = >33). Molecular modeling revealed that 19 was able to bind simultaneously to the CAS, mid-gorge and PAS sites of AChE and BuChE suggesting that it will be able to inhibit AChE induced Aβ aggregation. From this study, compounds that 3 and 19 can be considered as promising multifunctional lead compounds. Copyright © 2016 Elsevier Masson SAS. 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.

Solvent effects on the Raman spectra of the isolated carbon-hydrogen stretches of cyclohexane-d11: A molecular dynamics simulation study of liquid and supercritical solvation

NASA Astrophysics Data System (ADS)

Frankland, Sarah-Jane Victoria

Molecular dynamics simulations of solvent effects on the Raman spectra of isotopically isolated C-H stretches of cyclohexane-d11 were performed in liquids and supercritical CO2. The red spectral shifts from the gas phase origin were derived three different ways: (1) from the Lennard-Jones force on the normal coordinate of the vibration; (2) from this force with an additional term to account for the polarizabilily change on excitation, and (3) as an empirical difference potential between the v = 0 and v = 1 state of the hydrogen atom involved in the vibration. Model 3 was successfully parametrized to reproduce the experimental spectral shifts and linewidths. The simulated lineshapes from these models were homogeneously broadened from gas to liquid densities primarily by collisions of nearby solvent molecules with the solute. Both the simulations and isolated binary collision theory showed the density dependence of the linewidth to be related to that of the collision rate. Two additional projects were done which use Monte-Carlo algorithms involving two molecules. In the first project 1:1 complexes of solute and solvent were formed at the potential surface minima such that the geometries of conformers, energies of formation, and electronic spectral shifts could be studied. Complexes between 7- azaindole, indole, carbazole, and 1-azacarbazole and hydrogen-bonding solvents were most stable when the solvent was hydrogen-bonded at the solute N-H site. The energies of formation compared well with values obtained from ab initio calculations. Complexes of coumarins 102 and 153 and fluorinated alcohols showed the more stable conformers to have the alcohols bound at the coumarin carbonyl group. In the second project, one solvent molecule was randomly placed around the solute molecule in order to simplify bulk liquid simulation to only two molecules. This approximation was rised to show that the dynamic Stokes shift of coumarin 153 in over 30 solvents correlates with the permanent charge distribution of the solvent.

Dermal necrosis following coumarin: is it immunologically induced?

PubMed

Hislop, I G; Zilko, P J; Petersen, M; Ahmed, N

1980-02-01

Two patients with dermal necrosis due to anticoagulation therapy with warfarin are reported. Both patients demonstrated some disturbance in immunological function. It appears possible that warfarin may act as a hapten in the induction of hypersensitivity to the drug. It is recommended that future cases should be studied to determine whether there is a defect in immunoregulation, and whether circulating immune complexes are responsible for the typical skin lesions.

A ditopic fluorescence sensor for saccharides and mercury based on a boronic-acid receptor and desulfurisation reaction.

PubMed

Xing, Zhitao; Wang, Hui-Chen; Cheng, Yixiang; James, Tony D; Zhu, Chengjian

2011-11-04

Two boron-contained fluorescent sensors, 1 and 2, based on coumarin have been prepared. The fluorescence response of the two systems was investigated with addition of saccharide and mercury ions. Sensor 2 behaves as a bifunctional fluorescent switch with chemical inputs of D-fructose and mercury ions. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

[Pulmonary embolism following percutaneous vertebroplasty].

PubMed

Bedini, Marianela Patricia; Albertini, Ricarso Arturo; Orozco, Santiago

2013-01-01

Vertebroplasty is a minimally invasive technique for the treatment of osteoporotic fractures. Within its complications is pulmonary embolism, which can be asymptomatic or with respiratory distress and may be notes by radiography or computed tomography. At present there is no guide to indicate the routine performance of imaging techniques after treatment, and all agreed on the need to start anticoagulant therapy for 3 months or so with coumarin in symptomatic or asymptomatic central emboli.

Obtaining a Dry Extract from the Mikania laevigata Leaves with Potential for Antiulcer Activity

PubMed Central

Pinto, Mariana Viana; Oliveira, Ezequiane Machado; Martins, Jose Luiz Rodrigues; de Paula, Jose Realino; Costa, Elson Alves; da Conceição, Edemilson Cardoso; Bara, Maria Teresa Freitas

2017-01-01

Background: Mikania laevigata leaves are commonly used in Brazil as a medicinal plant. Objective: To obtain hydroalcoholic dried extract by nebulization and evaluate its antiulcerogenic potential. Materials and Methods: Plant material and hydroalcoholic extract were processed and analyzed for their physicochemical characteristics. A method using HPLC was validated to quantify coumarin and o-coumaric acid. Hydroalcoholic extract was spray dried and the powder obtained was characterized in terms of its physicochemical parameters and potential for antiulcerogenic activity. Results: The analytical method proved to be selective, linear, precise, accurate, sensitive, and robust. M. laevigata spray dried extract was obtained using colloidal silicon dioxide as adjuvant and was shown to possess 1.83 ± 0.004% coumarin and 0.80 ± 0.012% o-coumaric acid. It showed significant antiulcer activity in a model of an indomethacin-induced gastric lesion in mice and also produced a gastroprotective effect. Conclusion: This dried extract from M. laevigata could be a promising intermediate phytopharmaceutical product. SUMMARY Research and development of standardized dried extract of Mikania laevigata leaves obtained through spray drying and the production process was monitored by the chemical profile, physicochemical properties and potential for anti-ulcerogenic activity. Abbreviations used: DE: M. laevigata spray dried extract, HE: hydroalcoholic extract. PMID:28216886

Investigation of the biotransformation of osthole by liquid chromatography/tandem mass spectrometry.

PubMed

Li, Jie; Chan, Wan

2013-02-23

Osthole is an active ingredient and one of the major coumarin compounds that were identified in the genus Cnidium moonnieri (L.) Cussion, the fruit of which was used as traditional Chinese medicine to treat male impotence, ringworm infection and blood stasis conventionally. Recent studies revealed that osthole has diverse pharmacological effects, such as improving male sexual dysfunction, anti-diabetes, and anti-hypertentions. The inhibition of thrombosis and platelet aggregation and protection of central nerve were also observed. On the other hand, the metabolism of osthole has not yet been investigated thoroughly. Herein the biotransformation of osthole in rat was investigated after oral administration of osthole by using efficient and sensitive ultra-performance liquid chromatography-tandem quadrupole-time of flight mass spectrometry (UPLC-QTOF/MS). Eighteen osthole metabolites and the parent drug were detected and identified in rat urine. Fourteen metabolites of osthole were identified and characterized for the first time. Structures of metabolites of osthole were elucidated by comparing fragment pattern under MS/MS scan and change of molecular weight with those of osthole. The main phase I metabolic pathways were summed as 7-demethylation, 8-dehydrogenation, hydroxylation on coumarin and 3,4-epoxide. Sulfate conjugates were detected as phase II metabolites of osthole. Copyright © 2012 Elsevier B.V. All rights reserved.

Protective effects of osthole, a natural derivative of coumarin, against intestinal ischemia-reperfusion injury in mice.

PubMed

Dong, Wenpeng; Zhang, Zhen; Liu, Zhengjun; Liu, Hao; Wang, Xianyue; Bi, Shenghui; Wang, Xiaowu; Ma, Tao; Zhang, Weida

2013-06-01

Intestinal ischemia/reperfusion (I/R) injury is considered to be associated with high morbidity and mortality rates. Osthole, a natural derivative of coumarin, has been shown to exert a variety of pharmacological and therapeutic effects under physiological and pathological conditions. In the present study, to investigate the protective effects of osthole against intestinal I/R injury, various doses of osthole (5, 10, 25 and 50 mg/kg) were pre-administered to mice subjected to intestinal I/R injury. A dose-dependent increase in the survival rate was observed in the osthole-treated mice. Pre-treatment with osthole (50 mg/kg) attenuated the destruction of epithelial cells within the villi induced by intestinal I/R injury, and suppressed oxidative stress, neutrophil infiltration and modulated nitric oxide (NO) levels. Moreover, the increased IκBα phosphorylation and nuclear factor (NF)-κB nuclear translocation induced by I/R injury were significantly decreased following pre-treatment with osthole. Taken together, our data demonstrate that osthole exerts protective effects against intestinal I/R injury in mice by suppressing oxidative stress, neutrophil infiltration and NO levels, partly through the inhibition of NF-κB nuclear translocation. Hence, the findings of the present study provide insight into the mechanisms through which osthole exerts its protective effects against intestinal I/R injury.

In Silico Discovery of Novel Potent Antioxidants on the Basis of Pulvinic Acid and Coumarine Derivatives and Their Experimental Evaluation

PubMed Central

Martinčič, Rok; Mravljak, Janez; Švajger, Urban; Perdih, Andrej; Anderluh, Marko; Novič, Marjana

2015-01-01

A pigment from the edible mushroom Xerocomus badius norbadione A, which is a natural derivative of pulvinic acid, was found to possess antioxidant properties. Since the pulvinic acid represents a novel antioxidant scaffold, several other derivatives were recently synthetized and evaluated experimentally, along with some structurally related coumarine derivatives. The obtained data formed the basis for the construction of several quantitative structure-activity and pharmacophore models, which were employed in the virtual screening experiments of compound libraries and for the prediction of their antioxidant activity, with the goal of discovering novel compounds possessing antioxidant properties. A final prioritization list of 21 novel compounds alongside 8 established antioxidant compounds was created for their experimental evaluation, consisting of the DPPH assay, 2-deoxyribose assay, β-carotene bleaching assay and the cellular antioxidant activity assay. Ten novel compounds from the tetronic acid and barbituric acid chemical classes displayed promising antioxidant activity in at least one of the used assays, that is comparable to or even better than some standard antioxidants. Compounds 5, 7 and 9 displayed good activity in all the assays, and were furthermore effective preventers of oxidative stress in human peripheral blood mononuclear cells, which are promising features for the potential therapeutic use of such compounds. PMID:26474393

Design of butterfly type organic dye sensitizers with double electron donors: The first principle study

NASA Astrophysics Data System (ADS)

Yang, Zhenqing; Shao, Di; Li, Juan; Tang, Lian; Shao, Changjin

2018-05-01

In this work, we designed a series of butterfly type organic dyes, named ME07-ME13 by introducing such as triphenylamine, phenothiazine, coumarin groups etc. as electron donors and further investigated their absorption spectra using density functional theory (DFT) and time-dependent DFT (TDDFT). All designed dyes cover the entire visible absorption spectrum from 300 to 800 nm. It's fascinating that ME13 molecule has two absorption peak and the molar coefficient of two absorption peaks are above 4.645 × 104 M-1·cm-1. The light absorption area of ME13 exhibits an increment of 16.5-19.1% compared to ME07-ME12. Furthermore, we performed a detailed analysis on their geometrical and electronic properties, including molecular structures, energy levels, light harvesting efficiency (LHE), driving force (ΔGinject), regeneration (ΔGregen),electron dipole moments (μnormal), intermolecular electron transfer and dye/(TiO2)38 system electron transitions. The results of calculation reveal that double coumarin donors in ME13 are promising functional groups for butterfly type organic dye sensitizers. It is expected that the design of double donors can provide a new strategy and guidance for the investigation in high efficiency dye-sensitized devices.

Simultaneous determination of five minor coumarins and flavonoids in Glycyrrhiza uralensis by solid-phase extraction and high-performance liquid chromatography/electrospray ionization tandem mass spectrometry.

PubMed

Qiao, Xue; Liu, Chun-Fang; Ji, Shuai; Lin, Xiong-Hao; Guo, De-An; Ye, Min

2014-02-01

Minor phenolic compounds in licorice (Glycyrrhiza uralensis) have recently been proved for diverse bioactivities and favorable bioavailability, indicating that they may play an important role in the therapeutic effects or herb-drug interactions of licorice. However, so far, their abundance in licorice remains unknown. In this study, a reliable solid-phase extraction coupled with a high-performance liquid chromatography and diode array detection method was established to determine the minor phenolic compounds in licorice. The analytes were enriched by a three-step solid-phase extraction method, and then separated on a YMC ODS-A column by gradient elution. Five coumarins and flavonoids were identified by electrospray ionization tandem mass spectrometry, and then quantified using high-performance liquid chromatography and diode array detection. The amounts of glycycoumarin, dehydroglyasperin C, glycyrol, licoflavonol, and glycyrin in G. uralensis were 0.81 ± 0.28, 1.25 ± 0.59, 0.20 ± 0.08, 0.12 ± 0.04, and 0.17 ± 0.08 mg/g, respectively. Abundances of these compounds in other Glycyrrhiza species (G. glabra, G. inflata, and G. yunnanesis) were remarkably lower than G. uralensis. Georg Thieme Verlag KG Stuttgart · New York.

Simultaneous quantification of coumarins, flavonoids and limonoids in Fructus Citri Sarcodactylis by high performance liquid chromatography coupled with diode array detector.

PubMed

Chu, Jun; Li, Song-Lin; Yin, Zhi-Qi; Ye, Wen-Cai; Zhang, Qing-Wen

2012-07-01

A high performance liquid chromatography coupled with diode array detector (HPLC-DAD) method was developed for simultaneous quantification of eleven major bioactive components including six coumarins, three flavonoids and two limonoids in Fructus Citri Sarcodactylis. The analysis was performed on a Cosmosil 5 C(18)-MS-II column (4.6 mm × 250 mm, 5 μm) with water-acetonitrile gradient elution. The method was validated in terms of linearity, sensitivity, precision, stability and accuracy. It was found that the calibration curves for all analytes showed good linearity (R(2)>0.9993) within the test ranges. The overall limit of detection (LOD) and limit of quantification (LOQ) were less than 3.0 and 10.2 ng. The relative standard deviations (RSDs) for intra- and inter-day repeatability were not more than 4.99% and 4.92%, respectively. The sample was stable for at least 48 h. The spike recoveries of eleven components were 95.1-104.9%. The established method was successfully applied to determine eleven components in three samples from different locations. The results showed that the newly developed HPLC-DAD method was linear, sensitive, precise and accurate, and could be used for quality control of Fructus Citri Sarcodactylis. Copyright © 2012 Elsevier B.V. All rights reserved.

Molecular modification of coumarin dyes for more efficient dye sensitized solar cells

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

Sanchez-de-Armas, Rocio; San-Miguel, Miguel A.; Oviedo, Jaime

2012-05-21

In this work, new coumarin based dyes for dye sensitized solar cells (DSSC) have been designed by introducing several substituent groups in different positions of the NKX-2311 structure. Two types of substitutions have been considered: the introduction of three electron-donating groups (-OH, -NH{sub 2}, and -OCH{sub 3}) and two different substituents with steric effect: -CH{sub 2}-CH{sub 2}-CH{sub 2}- and -CH{sub 2}-HC=CH-. The electronic absorption spectra (position and width of the first band and absorption threshold) and the position of the LUMO level related to the conduction band have been used as theoretical criteria to evaluate the efficiency of the newmore » dyes. The introduction of a -NH{sub 2} group produces a redshift of the absorption maximum position and the absorption threshold, which could improve the cell efficiency. In contrast, the introduction of -CH{sub 2}-CH{sub 2}-CH{sub 2}- does not modify significantly the electronic structure of NKX-2311, but it might prevent aggregation. Finally, -CH{sub 2}-HC=CH- produces important changes both in the electronic spectrum and in the electronic structure of the dye, and it would be expected as an improvement of cell efficiency for these dyes.« less

Degradation-by-design: Surface modification with functional substrates that enhance the enzymatic degradation of carbon nanotubes.

PubMed

Sureshbabu, Adukamparai Rajukrishnan; Kurapati, Rajendra; Russier, Julie; Ménard-Moyon, Cécilia; Bartolini, Isacco; Meneghetti, Moreno; Kostarelos, Kostas; Bianco, Alberto

2015-12-01

Biodegradation of carbon-based nanomaterials has been pursued intensively in the last few years, as one of the most crucial issues for the design of safe, clinically relevant conjugates for biomedical applications. In this paper it is demonstrated that specific functional molecules can enhance the catalytic activity of horseradish peroxidase (HRP) and xanthine oxidase (XO) for the degradation of carbon nanotubes. Two different azido coumarins and one cathecol derivative are linked to multi-walled carbon nanotubes (MWCNTs). These molecules are good reducing substrates and strong redox mediators to enhance the catalytic activity of HRP. XO, known to metabolize various molecules mainly in the mammalian liver, including human, was instead used to test the biodegradability of MWCNTs modified with an azido purine. The products of the biodegradation process are characterized by transmission electron microscopy and Raman spectroscopy. The results indicate that coumarin and catechol moieties have enhanced the biodegradation of MWCNTs compared to oxidized nanotubes, likely due to the capacity of these substrates to better interact with and activate HRP. Although azido purine-MWCNTs are degraded less effectively by XO than oxidized nanotubes, the data uncover the importance of XO in the biodegradation of carbon-nanomaterials leading to their better surface engineering for biomedical applications. Copyright © 2015 Elsevier Ltd. All rights reserved.

Safety evaluation of the temporary consolidant based on a zebrafish embryo model.

PubMed

Zhang, Lu; Zhang, Xiao Yan; Hu, Yulan; Zhang, Bing Jian

2018-05-07

Temporary consolidants, such as cyclododecane, menthol, coumarin, and ethyl maltol, are proved to be effective for urgent conservation in archaeological field. However, the safety of these temporary consolidants is still unknown although they are always heavily used in archaeological field. Thus reports on the toxicity of these temporary consolidants are limited. Here, a zebrafish model was used for safety evaluation of these four temporary consolidants. In the present study, four temporary consolidants, including cyclododecane, menthol, coumarin, and ethyl maltol, at different concentrations were incubated with zebrafish embryos, and their biological toxic effects were firstly evaluated. It was shown that embryo exposure to temporary consolidants resulted in an increased mortality and malformation rate, and a decreased hatching rate. The order of embryo toxicity of the four types of temporary consolidants tested was menthol > coumarin > ethyl maltol > cyclododecane. Although the embryo toxicity of cyclododecane was minimal, some studies have indicated that this temporary consolidant could be bioaccumulated. The results also suggested that the zebrafish embryos can serve as a reliable model for the evaluation of embryo toxicity of temporary consolidants, as this model could offer the possibility to perform the rapid, medium throughput, cost-effective analyses. Copyright © 2018 Elsevier Ltd. All rights reserved.

Dye based photodiodes for solar energy applications

NASA Astrophysics Data System (ADS)

Mensah-Darkwa, K.; Ocaya, R.; Dere, A.; Al-Sehemi, Abdullah G.; Al-Ghamdi, Ahmed A.; Soylu, M.; Gupta, R. K.; Yakuphanoglu, F.

2017-10-01

Coumarin (CO) doped methylene blue (MB) organic photo-devices were fabricated. The CO-doped MB (0.00, 0.01, 0.03, 0.05, 0.1 wt% CO) were coated onto the surface of a p-type Si substrate by drop casting method. Some electrical parameters of the devices have been examined by current-voltage ( I- V), capacitance-voltage ( C- V), and conductance-voltage ( G- V) measurements. The fabricated devices had excellent rectifying properties. The diode exhibits a non-ideal diode behavior due to the series resistance and interface layer. The ideality factor, the barrier height, and the series resistance values of the diode as a function of doping and light illumination have been estimated using modified Cheung-Cheung and Norde's method. The highest I photo/ I dark photosensitivity of 5606 was observed for the diode having 0.01 CO doping at 100 mW/cm2 under -3 V. Furthermore, change of capacitance and conductance measurements with frequency is related to the existence of interface states. A maximum power conversion efficiency of 2.4% is estimated for the fabricated devices. The results reveal that coumarin-doped methylene blue/ p-Si heterojunction can be used as a photodiode in optoelectronic applications. It is also usable in low-power photovoltaic applications.

New generation of amino coumarin methyl sulfonate-based fluorogenic substrates for amidase assays in droplet-based microfluidic applications.

PubMed

Woronoff, Gabrielle; El Harrak, Abdeslam; Mayot, Estelle; Schicke, Olivier; Miller, Oliver J; Soumillion, Patrice; Griffiths, Andrew D; Ryckelynck, Michael

2011-04-15

Droplet-based microfluidics is a powerful tool for biology and chemistry as it allows the production and the manipulation of picoliter-size droplets acting as individual reactors. In this format, high-sensitivity assays are typically based on fluorescence, so fluorophore exchange between droplets must be avoided. Fluorogenic substrates based on the coumarin leaving group are widely used to measure a variety of enzymatic activities, but their application in droplet-based microfluidic systems is severely impaired by the fast transport of the fluorescent product between compartments. Here we report the synthesis of new amidase fluorogenic substrates based on 7-aminocoumarin-4-methanesulfonic acid (ACMS), a highly water-soluble dye, and their suitability for droplet-based microfluidics applications. Both substrate and product had the required spectral characteristics and remained confined in droplets from hours to days. As a model experiment, a phenylacetylated ACMS was synthesized and used as a fluorogenic substrate of Escherichia coli penicillin G acylase. Kinetic parameters (k(cat) and K(M)) measured in bulk and in droplets on-chip were very similar, demonstrating the suitability of this synthesis strategy to produce a variety of ACMS-based substrates for assaying amidase activities both in microtiter plate and droplet-based microfluidic formats. © 2011 American Chemical Society

Natural products as sources of new lead compounds for the treatment of Alzheimer's disease.

PubMed

Huang, Ling; Su, Tao; Li, Xingshu

2013-01-01

Alzheimer's disease (AD) is the most prevalent form of dementia and affects approximately 24 million people worldwide. One possible approach for the treatment of this disease is the restoration of the level of acetylcholine (ACh) through the inhibition of acetylcholinesterase (AChE) with reversible inhibitors. Naturally occurring alkaloids are an important source of AChE inhibitors. Galantamine and huperzine A have been used for the clinical treatment of AD patients. In this review, we summarise the natural products and their derivatives that were reported to act as AChE inhibitors for the treatment of AD in 2010-2013. Several characteristics were summarised from the literature results: 1) Amongst all of the natural products with AChE inhibitory activity, alkaloids appear to be the most promising compound class. 2) Coumarins, flavonoids, stilbenes, and other natural products are also important AChE inhibitors from natural products. Among these inhibitors, 146 (IC50 = 0.573 µM) was identified as the most potent AChE inhibitor. 3) A coumarin derivative (117, IC50 = 0.11 nM) exhibited more than 100-fold superior activity compared with the reference drug donepezil hydrochloride (IC50 = 14 nM). In conclusion, natural products and their derivatives are promising leads for the development of new drugs for the future treatment of AD.

Decursin attenuates kainic acid-induced seizures in mice.

PubMed

Lee, Jong-Keun; Jeong, Ji Woon; Jang, Taeik; Lee, Go-Woon; Han, Hogyu; Kang, Jae-Seon; Kim, Ik-Hwan

2014-11-12

Epilepsy is a neurological disorder with recurrent unprovoked seizures as the main symptom. Of the coumarin derivatives in Angelica gigas, decursin, a major coumarin component, was reported to exhibit significant protective activity against glutamate-induced neurotoxicity when added to primary cultures of rat cortical cells. This study served to investigate the effects of decursin on a kainic acid (KA)-induced status epilepticus model. Thirty minutes after intraperitoneal injections of decursin (20 mg/kg) in male 7-week-old C57BL/6 mice, the animals were treated with KA (30 mg/kg, intraperitoneally) and then examined for behavioral seizure score, electroencephalogram, seizure-related expressed protein levels, neuronal cell loss, neurodegeneration, and astrogliosis. KA injections significantly enhanced neurodegenerative conditions but treatment with decursin 30 min before KA injection reduced the detrimental effects of KA in mice. The decursin-treated KA-injected group showed significantly decreased behavioral seizure activity and remarkably attenuated intense and high-frequency seizure discharges in the parietal cortex for 2 h compared with the group treated only with KA. Furthermore, in-vivo results indicated that decursin strongly inhibits selective neuronal death, astrogliosis, and oxidative stress induced by KA administration. Therefore decursin is able to attenuate KA-induced seizures and could have potential as an antiepileptic drug.

Dermal absorption behavior of fluorescent molecules in nanoparticles on human and porcine skin models.

PubMed

Debotton, Nir; Badihi, Amit; Robinpour, Mano; Enk, Claes D; Benita, Simon

2017-05-30

The percutaneous passage of poorly skin absorbed molecules can be improved using nanocarriers, particularly biodegradable polymeric nanospheres (NSs) or nanocapsules (NCs). However, penetration of the encapsulated molecules may be affected by other factors than the nanocarrier properties. To gain insight information on the skin absorption of two fluorescent cargos, DiIC 18 (5) and coumarin-6 were incorporated in NSs or NCs and topically applied on various human and porcine skin samples. 3D imaging techniques suggest that NSs and NCs enhanced deep dermal penetration of both probes similarly, when applied on excised human skin irrespective of the nature of the cargo. However, when ex vivo pig skin was utilized, the cutaneous absorption of DiIC 18 (5) was more pronounced by means of PLGA NCs than NSs. In contrast, PLGA NSs noticeably improved the porcine skin penetration of coumarin-6, as compared to the NCs. Furthermore, the porcine skin results were reproducible when triplicated whereas from various human skin samples, as expected, the results were not sufficiently reproducible and large deviations were observed. The overall findings from this comprehensive comparison emphasize the potential of PLGA NCs or NSs to promote cutaneous bioavailability of encapsulated drugs, exhibiting different physicochemical properties but depending on the nature of the skin. Copyright © 2017 Elsevier B.V. All rights reserved.

Use of a small molecule as an initiator for interchain staudinger reaction: A new ATP sensing platform using product fluorescence.

PubMed

Yu, Huan; Zheng, Jing; Yang, Sheng; Asiri, Abdullah M; Alamry, Khalid A; Sun, Mingtai; Zhang, Kui; Wang, Suhua; Yang, Ronghua

2018-02-01

We demonstrated that a small molecule induced interchain Staudinger reaction can be employed for highly selective detection of adenosine triphosphate (ATP), an important energy-storage biomolecule. A designed ATP split aptamer (A1) was first functionalized with a weakly fluorescent coumarin derivative due to an azide group (azido-coumarin). The second DNA strand (A2) was covalently linked with triphenylphosphine, which could selectively and efficiently reduce azido to amino group through the Staudinger reaction. The A2 was then hybridized with a half of another designed longer DNA strand (T1). The second half of T1 was a split aptamer and selectively recognized ATP with A1 to form a sandwich structure. The specific interaction between ATP and the aptamers drew the two functionalized DNA strands (A1 and A2) together to initiate the interchain Staudinger reduction at fmol-nmol concentration level, hence produced fluorescent 7-aminocoumarin which could be used as an indicator for the presence of trace ATP. The reaction process had a concentration dependent manner with ATP in a large concentration range. Such a strategy of interchain Staudinger reaction can be extended to construct biosensors for other small functional molecules on the basis of judiciously designed aptamers. Copyright © 2017 Elsevier B.V. All rights reserved.

Synthesis of some novel orcinol based coumarin triazole hybrids with capabilities to inhibit RANKL-induced osteoclastogenesis through NF-κB signaling pathway.

PubMed

Rama Krishna, Boddu; Thummuri, Dinesh; Naidu, V G M; Ramakrishna, Sistla; Venkata Mallavadhani, Uppuluri

2018-08-01

A total of twenty-two novel coumarin triazole hybrids (4a-4k and 6a-6k) were synthesized from orcinol in good to excellent yields of 70-94%. The structures of all the synthesized compounds were elucidated by spectroscopic techniques such as 1 H NMR, 13 C NMR, and HRMS. The anti-inflammatory potential of synthesized compounds was investigated against the proinflammatory cytokine, TNF-α on U937 cell line and compounds 4d, 4j, and 6j were found to exhibit promising anti-inflammatory activity. These three compounds were further screened against TNF-α on LPS-stimulated RAW 264.7 cells, which confirm their anti-inflammatory potential. Furthermore, the above said active compounds were tested for their inhibitory effect on RANKL-induced osteoclastogenesis in RAW 264.7 cells by using tartrate resistant acid phosphatase (TRAP) staining assay at 10 µM. Molecular mechanism studies demonstrated that compound 4d exhibited dose dependent inhibition of RANKL-induced osteoclastogenesis by suppression of the NF-kB pathway. Thus, compound 4d is a promising candidate for further optimization to develop as a potent anti-osteoporotic agent. Copyright © 2018 Elsevier Inc. All rights reserved.

A study of the relationship between the chemical structures and the fluorescence quantum yields of coumarins, quinoxalinones and benzoxazinones for the development of sensitive fluorescent derivatization reagents.

PubMed

Azuma, Kentaro; Suzuki, Sachiko; Uchiyama, Seiichi; Kajiro, Toshi; Santa, Tomofumi; Imai, Kazuhiro

2003-04-01

To develop new fluorescent derivatization reagents, we investigated the relationship between the chemical structures and the fluorescence quantum yields (phi(f)) of coumarins, quinoxalinones and benzoxadinones. Forty-six compounds were synthesized and their fluorescence spectra were measured in n-hexane, ethyl acetate, methanol and water. The energy levels of these compounds were calculated by combination of the semi-empirical AM1 and INDO/S (CI = all) methods. The deltaE(Tn(n,pi*), S1(pi,pi*)) (the energy gap between the Tn(n,pi*) and S1(pi,pi*) states) values were well correlated with the phi(f) values, which enables us to predict the phi(f) values from their chemical structures. Based on this relationship, 3-phenyl-7-N-piperazinoquinoxalin-2(1H)-one (PQ-Pz) and 7-(3-(S)-aminopyrrolidin-1-yl)-3-phenylquinoxalin-2-(1H)-one (PQ-APy) were developed as fluorescent derivatization reagents for carboxylic acids. The derivatives of the carboxylic acids with PQ-Pz and PQ-APy showed large phi(f) values even in polar solvents, suggesting that these reagents are suitable for the microanalysis of biologically important carboxylic acids by reversed phase HPLC.

Triphenylamine Derived 3-Acetyl and 3-Benzothiazolyl Bis and Tris Coumarins: Synthesis, Photophysical and DFT Assisted Hyperpolarizability Study

NASA Astrophysics Data System (ADS)

Erande, Yogesh; Kothavale, Shantaram; Sreenath, Mavila C.; Chitrambalam, Subramaniyan; Joe, Isaac H.; Sekar, Nagaiyan

2018-02-01

Triphenylamine derived bis- and tris-branched donor-pi-acceptor coumarins with acetyl and benzothiazolyl acceptors are studied for their linear and nonlinear optical properties that originate from their photophysical and molecular structure. Plots of solvent polarities versus the Stokes shift, frontier molecular orbital analysis and Generalised Mulliken Hush analysis have established their strong charge transfer character supported by the strong emission solvatochromism of these chromophores. On the basis of excited state intramolecular charge transfer, the first-, second- and third-order polarizability of these dyes are determined by a solvatochromic method and supported by density functional theory calculations using CAM-B3LYP/6-31g(d). Compared to the acetyl group, the benzothiazolyl group is a strong acceptor, and its corresponding derivatives show enhanced absorption, emission maxima and non-linear optical response. Bond length alternation and bond order alternation analysis reveals that these chromophores approach the cyanine-like framework which is responsible for maximum perturbation to produce high nonlinear optical response. Third order nonlinear susceptibility for dyes 1 and 2 is determined by Z-scan measurement. All of these methods are used to determine the nonlinear optical properties, and thermogravimetric analysis suggests that these chromophores are thermally robust and efficient nonlinear optical materials.

Discovery of a novel class of potent coumarin monoamine oxidase B inhibitors: development and biopharmacological profiling of 7-[(3-chlorobenzyl)oxy]-4-[(methylamino)methyl]-2H-chromen-2-one methanesulfonate (NW-1772) as a highly potent, selective, reversible, and orally active monoamine oxidase B inhibitor.

PubMed

Pisani, Leonardo; Muncipinto, Giovanni; Miscioscia, Teresa Fabiola; Nicolotti, Orazio; Leonetti, Francesco; Catto, Marco; Caccia, Carla; Salvati, Patricia; Soto-Otero, Ramon; Mendez-Alvarez, Estefania; Passeleu, Celine; Carotti, Angelo

2009-11-12

In an effort to discover novel selective monoamine oxidase (MAO) B inhibitors with favorable physicochemical and pharmacokinetic profiles, 7-[(m-halogeno)benzyloxy]coumarins bearing properly selected polar substituents at position 4 were designed, synthesized, and evaluated as MAO inhibitors. Several compounds with MAO-B inhibitory activity in the nanomolar range and excellent MAO-B selectivity (selectivity index SI > 400) were identified. Structure-affinity relationships and docking simulations provided valuable insights into the enzyme-inhibitor binding interactions at position 4, which has been poorly explored. Furthermore, computational and experimental studies led to the identification and biopharmacological characterization of 7-[(3-chlorobenzyl)oxy]-4-[(methylamino)methyl]-2H-chromen-2-one methanesulfonate 22b (NW-1772) as an in vitro and in vivo potent and selective MAO-B inhibitor, with rapid blood-brain barrier penetration, short-acting and reversible inhibitory activity, slight inhibition of selected cytochrome P450s, and low in vitro toxicity. On the basis of this preliminary preclinical profile, inhibitor 22b might be viewed as a promising clinical candidate for the treatment of neurodegenerative diseases.

Proteomic characterization of Aspergillus fumigatus treated with an antifungal coumarin for identification of novel target molecules of key pathways.

PubMed

Singh, Seema; Gupta, Shilpi; Singh, Bharat; Sharma, Sunil K; Gupta, Vijay K; Sharma, Gainda L

2012-06-01

A synthetic coumarin, N,N,N-triethyl-11-(4-methyl-2-oxo-2H-chromen-7-yloxy)-11-oxoundecan-1-aminium bromide (SCD-1), having potent activity against pathogenic Aspergilli (MIC90 15.62 μg/mL), was investigated to identify its molecular targets in the pathogen. The proteome of Aspergillus fumigatus was developed after treatment with sublethal doses of compound and analyzed. The results demonstrated 143 differentially expressed proteins on treatment with SCD-1. The expression of four proteins, namely cell division control protein, ubiquitin-like activating enzyme, vacuolar ATP synthase catalytic subunit A, and UTP-glucose-1-phosphate uridylyltransferase of A. fumigatus, was completely inhibited, whereas there were 13 newly expressed and 96 overexpressed proteins, mainly belonging to stress pathway. The treatment of A. fumigatus with SCD-1 also led to attenuation of proteins involved in cell replication and other important biosynthetic processes, including riboflavin biosynthesis, which has been pathogen-specific. In addition to key enzymatic players and antioxidants, nine hypothetical proteins were also identified, seven of which have been novel, being described for the first time. As no cellular functions have yet been described for these hypothetical proteins, their alteration in response to SCD-1 provides significant information about their putative roles in pathogen defense.

Bioactive natural compounds from the plant endophytic fungi Pestalotiopsis spp.

PubMed

Wang, Kuiwu; Lei, Jinxiu; Wei, Jiguang; Yao, Nan

2012-11-01

The plant-endophytic strains of the fungus Pestalotiopsis (Amphisphaeriaceae) are distributed throughout the world. Previous chemical investigation of members of the genus resulted in the discovery of various bioactive secondary metabolites including chromones, cytosporones, polyketides, terpenoids and coumarins with diverse structural features. The present report reviews the papers, which have appeared in the literature till now, concerning the isolation, structural elucidation, and biological activities of the secondary metabolites from Pestalotiopsis species.

Molecular Mechanisms of Prostate Cancer Progression

DTIC Science & Technology

2003-01-01

other drugs ( novobiocin and related hsp90 inhibitors have been shown to bind to the N-ter- coumarins) that are reported to target hsp90 are now be...undesirable for an indirect method of telomerase inhibition (data not shown). However, radicicol, which binds in the ATP- binding pocket of hsp90 and...compounds (e.g. novobiocin ) to block chaperone function using a totally different mechanism of hsp90 inhbition, as well as innovative genetic approaches

Understanding the Molecular Determinant of Reversible Human Monoamine Oxidase B Inhibitors Containing 2H-Chromen-2-One Core: Structure-Based and Ligand-Based Derived Three-Dimensional Quantitative Structure-Activity Relationships Predictive Models.

PubMed

Mladenović, Milan; Patsilinakos, Alexandros; Pirolli, Adele; Sabatino, Manuela; Ragno, Rino

2017-04-24

Monoamine oxidase B (MAO B) catalyzes the oxidative deamination of aryalkylamines neurotransmitters with concomitant reduction of oxygen to hydrogen peroxide. Consequently, the enzyme's malfunction can induce oxidative damage to mitochondrial DNA and mediates development of Parkinson's disease. Thus, MAO B emerges as a promising target for developing pharmaceuticals potentially useful to treat this vicious neurodegenerative condition. Aiming to contribute to the development of drugs with the reversible mechanism of MAO B inhibition only, herein, an extended in silico-in vitro procedure for the selection of novel MAO B inhibitors is demonstrated, including the following: (1) definition of optimized and validated structure-based three-dimensional (3-D) quantitative structure-activity relationships (QSAR) models derived from available cocrystallized inhibitor-MAO B complexes; (2) elaboration of SAR features for either irreversible or reversible MAO B inhibitors to characterize and improve coumarin-based inhibitor activity (Protein Data Bank ID: 2V61 ) as the most potent reversible lead compound; (3) definition of structure-based (SB) and ligand-based (LB) alignment rule assessments by which virtually any untested potential MAO B inhibitor might be evaluated; (4) predictive ability validation of the best 3-D QSAR model through SB/LB modeling of four coumarin-based external test sets (267 compounds); (5) design and SB/LB alignment of novel coumarin-based scaffolds experimentally validated through synthesis and biological evaluation in vitro. Due to the wide range of molecular diversity within the 3-D QSAR training set and derived features, the selected N probe-derived 3-D QSAR model proves to be a valuable tool for virtual screening (VS) of novel MAO B inhibitors and a platform for design, synthesis and evaluation of novel active structures. Accordingly, six highly active and selective MAO B inhibitors (picomolar to low nanomolar range of activity) were disclosed as a result of rational SB/LB 3D QSAR design; therefore, D123 (IC 50 = 0.83 nM, K i = 0.25 nM) and D124 (IC 50 = 0.97 nM, K i = 0.29 nM) are potential lead candidates as anti-Parkinson's drugs.

Two new compounds from the plant endophytic fungus Pestalotiopsis versicolor.

PubMed

Yang, Xiao-Long; Huang, Le; Li, Hai-Ying; Yang, Deng-Feng; Li, Zhuang-Zhuang

2015-01-01

A new coumarin, 4,6-dihydroxy-7-formyl-3-methylcoumarin (1), and an α-pyrone derivative, 6-[(7S,8R)-8-propyloxiran-1-yl]-4-methoxy-pyran-2-one (2), together with four known α-pyrone derivatives (3-6), were isolated from the broth extract of the plant endophytic fungus Pestalotiopsis versicolor. Their structures were elucidated by extensive spectroscopic analysis and by comparison of the chemical shift values with those of related known compounds.

Liquid scintillators for optical fiber applications

DOEpatents

Franks, Larry A.; Lutz, Stephen S.

1982-01-01

A multicomponent liquid scintillator solution for use as a radiation-to-light converter in conjunction with a fiber optic transmission system. The scintillator includes a quantity of 1, 2, 4, 5, 3H, 6H, 1 OH, tetrahydro-8-trifluoromethyl (1) benzopyrano (9, 9a, 1-gh) quinolizin-10-one (Coumarin) as a solute in a fluor solvent such as benzyl alcohol or pseudo-cumene. The use of BIBUQ as an additional or primary solute is also disclosed.

Identification of a coumarin based antihistamine as an anti filoviral entry inhibitor

DTIC Science & Technology

2017-06-20

Gharaibeh2, Tara Kenny2, Cary Retterer2, Rouzbeh Zamani2, Sina Bavari2, Norton P. Peet3 and Lijun Rong1 1. Department of Microbiology and Immunology...authors: Han Cheng, Department of Microbiology and Immunology, University of Illinois at Chicago, 8040 COMRB, 909 S. Wolcott Avenue, Chicago, IL 60612...Phone: (312)-996-0110 Fax: (312)- 996-6415 Email: hancheng@uic.edu Lijun Rong, Department of Microbiology and Immunology, University of Illinois at

The Coumarin Derivative Osthole Stimulates Adult Neural Stem Cells, Promotes Neurogenesis in the Hippocampus, and Ameliorates Cognitive Impairment in APP/PS1 Transgenic Mice.

PubMed

Kong, Liang; Hu, Yu; Yao, Yingjia; Jiao, Yanan; Li, Shaoheng; Yang, Jingxian

2015-01-01

It is believed that neuronal death caused by abnormal deposition of amyloid-beta peptide is the major cause of the cognitive decline in Alzheimer's disease. Adult neurogenesis plays a key role in the rescue of impaired neurons and amelioration of cognitive impairment. In the present study, we demonstrated that osthole, a natural coumarin derivative, was capable of promoting neuronal stem cell (NSC) survival and inducing NSC proliferation in vitro. In osthole-treated APP/PS1 transgenic mice, a significant improvement in learning and memory function was seen, which was associated with a significant increase in the number of new neurons (Ki67(+)/NF-M(+)) and a decrease in apoptotic cells in the hippocampal region of the brain. These observations suggested that osthole promoted NSC proliferation, supported neurogenesis, and thus efficiently rescued impaired neurons in the hippocampus and ameliorated cognitive impairment. We also found that osthole treatment activated the Notch pathway and upregulated the expression of self-renewal genes Notch 1 and Hes 1 mRNA in NSCs. However, when Notch activity was blocked by the γ-secretase inhibitor DAPT, the augmentation of Notch 1 and Hes 1 protein was ameliorated, and the proliferation-inducing effect of osthole was abolished, suggesting that the effects of osthole are at least in part mediated by activation of the Notch pathway.

Isolation and identification of metabolites of osthole in rats.

PubMed

Lv, X; Wang, C-Y; Hou, J; Zhang, B-J; Deng, S; Tian, Y; Huang, S-S; Zhang, H-L; Shu, X-H; Zhen, Y-H; Liu, K-X; Yao, J-H; Ma, X-C

2012-11-01

Osthole (Ost), one of the major components of Cnidium monnieri (L.) Cusson, is had the structure of an isopentenoxy-coumarin with a range of pharmacological activities. In the present study, the metabolism of Ost in male Sprague-Dawley rats was investigated by identifying Ost metabolites excreted in rat urine. Following an oral dose of 40 mg/kg Ost, 10 phase I and 3 phase II metabolites were isolated from the urine of rats, and their structures identified on the basis of a range of spectroscopic data, including 2D-NMR techniques. These metabolites were fully characterized as 5'-hydroxyl-osthole (M-1), osthenol (M-2), 4'-hydroxyl-osthole (M-3), 3, 5'-dihydroxyl-osthole (M-4), 5'-hydroxyl-osthenol (M-5), 4'-hydroxyl-2', 3'-dihydro-osthenol (M-6), 4'-hydroxyl-osthenol (M-7), 3, 4'-dihydroxyl-osthole (M-8), 2', 3'-dihydroxyl-osthole (M-9), 5'-hydroxyl-2', 3'-dihydroosthole (M-10), osthenol-7-O-β-D-glucuronide (M-11), osthole-4'-O-β-D-glucuronide (M-12) and osthole-5'-O-β-D-glycuronate (M-13). This is the first identification of M-1, M-3 to M-13 in vivo. On the basis of the metabolites profile, a possible metabolic pathway for Ost metabolism in rats has been proposed. This is the first systematic study on the phases I and II metabolites of 8-isopentenoxy-coumarin derivative.

Assessment of the genotoxic/clastogenic potential of coumarin derivative 6,7-dihydroxycoumarin (aesculetin) in multiple mouse organs.

PubMed

Marques, Eduardo de Souza; Salles, Daiane Bernardoni; Maistro, Edson Luis

2015-01-01

6,7-Dihydroxycoumarin (6,7-HC) (aesculetin) is a natural and synthetic coumarin derivative of great interest for use by humans due to their potent antioxidant properties. Considering that there are no reports that assess the in vivo genetic toxicity of 6,7-HC, the aim of the present study was to investigate its genotoxic potential in terms of DNA damage in peripheral blood, liver, bone marrow and testicular cells of Swiss albino mice by the comet assay, and its clastogenic/aneugenic potential in bone marrow cells using the micronucleus test. In addition, the ability of 6,7-HC to modulate the genotoxic effects induced by doxorubicin (DXR) was also preliminarily evaluated. Cytotoxicity was assessed by scoring polychromatic (PCE) and normochromatic (NCE) erythrocytes' ratio. The test compound was administered orally at doses of 25, 50 and 500 mg kg -1 isolated and also simultaneously to DXR (80 mg kg -1 ). The results showed that 6,7-HC did not induce significant DNA damage in any of the analyzed cells, and also did not show any significant increase in micronucleated PCE at the three tested doses. The PCE/NCE ratio indicated no cytotoxicity. Moreover, the extent of DNA damage induced by DXR decreased significantly only in peripheral blood and testicular cells, and only at the lowest dose of 6,7-HC.

Novel 2H-chromen-2-one derivatives of resveratrol: Design, synthesis, modeling and use as human monoamine oxidase inhibitors.

PubMed

Ruan, Ban-Feng; Cheng, Hui-Jie; Ren, Jing; Li, Hong-Lin; Guo, Lu-Lu; Zhang, Xing-Xing; Liao, Chenzhong

2015-10-20

Using a fragment-based drug design strategy, two biomedical interesting fragments, resveratrol and coumarin were linked to design a series of novel human monoamine oxidase (hMAO) inhibitors with a scaffold of 3-((E)-3-(2-((E)-styryl)phenyl)acryloyl)-2H-chromen-2-one, which demonstrated a very interesting selectivity profile against hMAO-A and hMAO-B: some compounds with this scaffold are selective hMAO-A inhibitors, whereas some are selective hMAO-B inhibitors. The small changes in the substituents of the coumarin moiety led to this interesting selectivity profile. The most potent selective hMAO-B inhibitor D7 has a selectivity ratio of 20.93, with an IC₅₀ value of 2.78 μM, similar or better than selegiline (IC₅₀ = 2.89 μM), a selective hMAO-B inhibitor currently in the market for the treatment of Parkinson's disease. Our modeling study indicates that Tyr 326 of hMAO-B (or corresponded Ile 335 of hMAO-A) may be the determinant for the specificity of these compounds. The selectivity profile of compounds reported herein suggests that we can further develop both selective hMAO-A and hMAO-B inhibitors based on this novel scaffold. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Methyl galbanate, a novel inhibitor of nitric oxide production in mouse macrophage RAW264.7 cells.

PubMed

Kohno, Susumu; Murata, Tomiyasu; Sugiura, Ayumi; Ito, Chihiro; Iranshahi, Mehrdad; Hikita, Kiyomi; Kaneda, Norio

2011-04-01

It is well known that inflammation is associated with various neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease. An inflammatory mediator, nitric oxide (NO), is produced by inducible NO synthase (iNOS) in microglia and seems to be one of the possible causes of neurodegeneration. Several natural and synthetic compounds which exert anti-inflammatory effects by inhibiting NO production have been reported to date. The aim of this work was to investigate whether any of the 6 terpenoid coumarins (methyl galbanate, galbanic acid, farnesiferol A, badrakemone, umbelliprenin, and aurapten) isolated from Ferula szowitsiana DC. have inhibitory activity against NO production in RAW264.7 mouse macrophage cells stimulated with lipopolysaccharide (LPS) and interferon-γ (IFN-γ). Of the 6 terpenoid coumarins tested, methyl galbanate significantly decreased NO production in LPS/IFN-γ-stimulated RAW264.7 cells. In the presence of methyl galbanate, LPS/IFN-γ-induced iNOS mRNA expression was significantly decreased to 52% of the level found with LPS/IFN-γ stimulation alone. Methyl galbanate slightly attenuated COX-2 mRNA expression. Using the RAW264.7-tsAM5NE co-culture system, we showed that methyl galbanate protected neuronally differentiated tsAM5NE cells from NO-induced cell death by inhibiting the production of NO. Our finding suggests that methyl galbanate may be useful for developing a new drug against neurodegenerative diseases.

Esculetin Inhibits the Survival of Human Prostate Cancer Cells by Inducing Apoptosis and Arresting the Cell Cycle.

PubMed

Turkekul, Kader; Colpan, R Dilsu; Baykul, Talha; Ozdemir, Mehmet D; Erdogan, Suat

2018-03-01

Prostate cancer (PCa) is one of the most important causes of death in men and thus new therapeutic approaches are needed. In this study, antiproliferative and anti-migration properties of a coumarin derivative esculetin were evaluated. Human PCa cell lines PC3, DU145, and LNCaP were treated with various concentrations of esculetin for 24 to 72 hours, and cell viability was determined by the MTT test. Cell cycle and apoptosis were analyzed by using cell-based cytometer. Gene expression levels were assessed by reverse transcription and quantitative real-time PCR, cell migration was determined by the wound healing assay. The protein expression was measured by Western blotting. Esculetin inhibited cell proliferation in a dose- and time-dependent manner. Cell migration was inhibited by esculetin treatment. Administration of esculetin significantly reduced the cells survival, induced apoptosis and caused the G1 phase cell cycle arrest shown by image-based cytometer. The induced expression of cytochrome c , p53, p21 and p27, and down-regulated CDK2 and CDK4 may be the underlying molecular mechanisms of esculetin effect. Esculetin suppressed phosphorylation of Akt and enhanced protein expression of tumor-suppressor phosphatase and tensin homologue. Our findings showed that the coumarin derivative esculetin could be used in the management of PCa. However, further in vivo research is needed.

Esculetin Inhibits the Survival of Human Prostate Cancer Cells by Inducing Apoptosis and Arresting the Cell Cycle

PubMed Central

Turkekul, Kader; Colpan, R. Dilsu; Baykul, Talha; Ozdemir, Mehmet D.

2018-01-01

Background Prostate cancer (PCa) is one of the most important causes of death in men and thus new therapeutic approaches are needed. In this study, antiproliferative and anti-migration properties of a coumarin derivative esculetin were evaluated. Methods Human PCa cell lines PC3, DU145, and LNCaP were treated with various concentrations of esculetin for 24 to 72 hours, and cell viability was determined by the MTT test. Cell cycle and apoptosis were analyzed by using cell-based cytometer. Gene expression levels were assessed by reverse transcription and quantitative real-time PCR, cell migration was determined by the wound healing assay. The protein expression was measured by Western blotting. Results Esculetin inhibited cell proliferation in a dose- and time-dependent manner. Cell migration was inhibited by esculetin treatment. Administration of esculetin significantly reduced the cells survival, induced apoptosis and caused the G1 phase cell cycle arrest shown by image-based cytometer. The induced expression of cytochrome c, p53, p21 and p27, and down-regulated CDK2 and CDK4 may be the underlying molecular mechanisms of esculetin effect. Esculetin suppressed phosphorylation of Akt and enhanced protein expression of tumor-suppressor phosphatase and tensin homologue. Conclusions Our findings showed that the coumarin derivative esculetin could be used in the management of PCa. However, further in vivo research is needed. PMID:29629344

Systematic chemical profiling of Citrus grandis 'Tomentosa' by ultra-fast liquid chromatography/diode-array detector/quadrupole time-of-flight tandem mass spectrometry.

PubMed

Li, Pan-lin; Liu, Meng-hua; Hu, Jie-hui; Su, Wei-wei

2014-03-01

Citrus grandis 'Tomentosa', as the original plant of the traditional Chinese medicine "Huajuhong", has been used as antitussive and expectorant in clinic for thousands of years. The fruit epicarp and whole fruit of this plant were both literarily recorded and commonly used. In the present study, an ultra-fast liquid chromatography coupled with diode-array detection and quadrupole/time-of-flight mass spectrometry (UFLC-DAD-Q-TOF-MS/MS) based chemical profiling method was developed for rapid holistic quality evaluation of C. grandis 'Tomentosa', which laid basis for chemical comparison of two medicinal parts. As a result, forty-eight constituents, mainly belonging to flavonoids and coumarins, were unambiguously identified by comparison with reference standards and/or tentatively characterized by elucidating UV spectra, quasi-molecular ions and fragment ions referring to information available in literature. Both of the epicarp and whole fruit samples were rich in flavonoids and coumarins, but major flavonoids contents in whole fruit were significantly higher than in epicarp (P<0.5). The proposed method could be useful in quality control and standardization of C. grandis 'Tomentosa' raw materials and its products. Results obtained in this study will provide a basis for quality assessment and further study in vivo. Copyright © 2013 Elsevier B.V. All rights reserved.

Integrated strategy based on high-resolution mass spectrometry coupled with multiple data mining techniques for the metabolic profiling of Xanthoceras sorbifolia Bunge husks in rat plasma, urine, and feces.

PubMed

Rong, Weiwei; Guo, Sirui; Ding, Kewen; Yuan, Ziyue; Li, Qing; Bi, Kaishun

2018-04-25

An integrated strategy based on high-resolution mass spectrometry coupled with multiple data mining techniques was developed to screen the metabolites in rat biological fluids after the oral administration of Xanthoceras sorbifolia Bunge husks. Mass defect filtering, product ion filtering, and neutral loss filtering were applied to detect metabolites from the complex matrix. As a result, 55 metabolites were tentatively identified, among which 45 barrigenol-type triterpenoid metabolites were detected in the feces, and six flavonoids and four coumarins metabolites were in the urine. Moreover, eight prototype constituents in plasma, 36 in urine and 23 in feces were also discovered. Due to the poor bioavailability of barrigenol type triterpenoids, most of them were metabolized by intestinal flora. Phase I metabolic reactions such as deglycosylation, oxidation, demethylation, dehydrogenation, and internal hydrolysis were supposed to be their principal metabolic pathways. Coumarins were found in all the biosamples, whereas flavonoids were mainly in the urine. Unlike the saponins, they were mainly metabolized through phase II metabolic reactions like glucuronidation and sulfonation, which made them eliminated more easily by urine. This work suggested the metabolic profile of X. sorbifolia husks for the first time, which will be very valuable for its further development. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Patch tests with fragrance mix II and its components.

PubMed

Pónyai, Györgyi; Németh, Ilona; Altmayer, Anita; Nagy, Gabriella; Irinyi, Beatrix; Battyáni, Zita; Temesvári, Erzsébet

2012-01-01

Fragrance mix II (FM II) was initiated to detect contact hypersenstitivity (CH) to fragrances that could not have been identified previously. The aim of this multicenter study was to map the frequency of CH to FM II and its components in Hungary. Six centers participated in the survey from 2009 to 2010. A total off 565 patients (434 women and 131 men) with former skin symptoms provoked by scented products were patch tested. The tests were performed with Brial GmbH D-Greven allergens. In the environmental patch test series, FM II, FM I, Myroxylon pereirae, colophonium, wood-tar mix, propolis, and sesquiterpene lactone mix were tested as fragrance allergens. The FM II components (citral, farnesol, coumarin, citronellol, α-hexyl-cinnamaldehyde, and hydroxy-isohexyl-3-cyclohexene-carboxaldehyde [Lyral]) were also tested. Contact hypersenstitivity to any fragrances was detected in 28.8%, to FM II in 17.2% of the patients. Contact hypersenstitivity to hydroxy-isohexyl-3-cyclohexene-carboxaldehyde was observed in 7.3%, to coumarin in 5.1%, to α-hexyl-cinnamaldehyde in 3.5%, to citral in 3.4%, to farnesol in 2.5%, and to citronellol in 1.2%. Of the FM II-positive cases, 48.4% showed isolated CH reaction. The frequency of CH to FM II is 17.2% in the tested, selected Hungarian population. The CH to FM II and its components could not have been revealed without the present test materials.

A quaternary ammonium modified coumarin derivative for antimicrobial photodynamic therapy

NASA Astrophysics Data System (ADS)

Sun, Zhiyuan; Zhou, Shaona; Gu, Ying; Zhao, Yuxia

2018-02-01

A new cationic modified coumarin derivative, 7-diethylamino-3-(3-(4-(trimethylbenzenaminium iodide) phenyl) acryloyl)-2H-chromen-2-one (1), was synthesized and characterized by 1H NMR and mass spectra. It had a strong intramolecular charge transfer absorption band around 460 nm with large molar extinction coefficients of 3.94 × 104 M-1 cm-1 in DMF and 3.86 × 104 M-1 cm-1 in PBS, respectively. Moreover, a moderate singlet oxygen quantum yield of 0.16 was obtained for 1 in DMF. Using methylene blue (MB) under a 630 nm laser as reference, the in vitro antimicrobial photodynamic therapy (aPDT) activity of 1 against three strains, gram positive bacteria methicillin-resistant staphylococcus aureus (MRSA), negative bacteria acinetobacter baumannii (A. baumannii) and fungus Candida albicans (C. albicans), was carried out by irradiation with a 457 nm laser. It was shown that 1 had no dark toxicity to these bacteria when its concentration was up to 100 μM, while under the 457 nm laser it could kill them effectively with an over 3 log CFU/ml decrease of the bacterial viability with its concentration up to 5 μM. The aPDT capability of 1 against MRSA and A. baumannii was equivalent to that of MB. For C. albicans, 1 exhibited much better aPDT effect than MB.

Gold nanocluster-based ratiometric fluorescent probes for hydrogen peroxide and enzymatic sensing of uric acid.

PubMed

Yang, Dongqin; Luo, Minchuan; Di, Junwei; Tu, Yifeng; Yan, Jilin

2018-05-18

A method is described for ratiometric fluorometric assays of H 2 O 2  by using two probes that have distinct response profiles. Under the catalytic action of ferrous ion, the 615 nm emission of protein-stabilized gold nanoclusters (under 365 nm photoexcitation) is quenched by H 2 O 2 , while an increased signal is generated with a peak at 450 nm by oxidizing coumarin with the H 2 O 2 /Fe(II) system to form a blue emitting fluorophore. These decrease/increase responses give a ratiometric signal. The ratio of the fluorescences at the two peaks are linearly related to the concentration of H 2 O 2 in the range from 0.05 to 10 μM, with a 7.7 nM limit of detection. The detection scheme was further coupled to the urate oxidase catalyzed oxidation of uric acid which proceeds under the formation of H 2 O 2 . This method provides an simple and effective means for the construction of ratiometric fluorometric (enzymatic) assays that involve the detection of H 2 O 2 . Graphical abstract Under catalysis by ferrous ion, hydrogen peroxide quenches the luminescence of gold nanoclusters (AuNCs) and oxidizes coumarin into a fluorescent derivative, which rendered fluorescence ON and OFF at two distinct wavelengths for ratiometric measurements.

Titanium(IV)-Catalyzed Stereoselective Synthesis of Spirooxindole-1-pyrrolines

PubMed Central

2015-01-01

A stereoselective cyclization between alkylidene oxindoles and 5-methoxyoxazoles has been developed using catalytic titanium(IV) chloride (as low as 5 mol %) to afford spiro[3,3′-oxindole-1-pyrrolines] in excellent yield (up to 99%) and diastereoselectivity (up to 99:1). Using a chiral scandium(III)–indapybox/BArF complex affords enantioenriched spirooxindole-1-pyrrolines where a ligand-induced reversal of diastereoselectivity is observed. This methodology is further demonstrated for the synthesis of pyrrolines from malonate alkylidene and coumarin derivatives. PMID:25474118

Molecular Evolution of Human PON to Design Enhanced Catalytic Efficiency for Hydrolysis of Nerve Agents

DTIC Science & Technology

2011-12-01

8   C.   Catalytic activity of evolved variants with GA ................................................................. 11   D...several variants of rePON1 with enhanced activity towards a racemic mixture of CMP-Coumarin by screening ‘neutral drift’ libraries of rePON1 (e.g. 1G3, 2G9...22. The most active variant was 3B3, which had ~250-fold higher catalytic efficiency (kcat/Km 20x106 M-1min-1) compared to the wild-type-like

An updated review on the parasitic herb of Cuscuta reflexa Roxb.

PubMed

Patel, Satish; Sharma, Vikas; Chauhan, Nagendra S; Dixit, Vinod K

2012-03-01

Cuscuta reflexa Roxb. is a golden yellow, leafless, perennial, parasitic herb of the family Convolvulaceae. C. reflexa has been investigated for antispasmodic, hemodynamic, anticonvulsant, anti steroidogenic, antihypertensive, muscle relaxant, cardiotonic, antiviral, antibacterial, antioxidant, cholinergic, diuretic and hair growth activities. Many chemical constituents have been isolated from C. reflexa such as cuscutin, amarbelin, β-sitosterol, stigmasterol, kaempferol, dulcitol, myricetin, quercetin, coumarin and oleanolic acid. This review presents a detailed survey of the literature on pharmacognosy, phytochemistry and traditional and biological medicinal uses of C. reflexa.

Chemiluminescence of Organic Peroxides: Intramolecular Electron-Exchange Luminescence from a Secondary Perester.

DTIC Science & Technology

1986-09-14

variety of conditions that would preserve the amino-coumarin functional group. Despite the commercial availability of 1 , Its synthesis has not been... synthesis of peresters and diacylperoxides12 . It was hoped that DCC would activate acid 1 in the presence of a secondary hydroperoxide and thereby...were used as received. 8-Methoxyjulolidine.14 3-Methoxyaniline (0.10 mol, 11 mL, 12.3 g), 1 -bromo-3- chloropropane (160 mL, 1.5 mol, 235 g) and

Applications of p-hydroxyphenacyl (pHP) and coumarin-4-ylmethyl photoremovable protecting groups.

PubMed

Givens, Richard S; Rubina, Marina; Wirz, Jakob

2012-03-01

Most applications of photoremovable protecting groups have used o-nitrobenzyl compounds and their (often commercially available) derivatives that, however, have several disadvantages. The focus of this review is on applications of the more recently developed title compounds, which are especially well suited for time-resolved biochemical and physiological investigations, because they release the caged substrates in high yield within a few nanoseconds or less. Together, these two chromophores cover the action spectrum for photorelease from >700 nm to 250 nm.

Limonoid from the rhizomes of Luvunga scandens (Roxb.) Buch. Ham.

PubMed

Nguyen, Tan Phat; Minh, Nhat Phan; Dat, Trong Bui; Le, Tien Dung; Tran Nguyen, Minh An; Pham, Thi Nhat Trinh; Tri, Dinh Mai

2017-10-01

For first time, the chemical constituents of the rhizomes of Luvunga scandens (Roxb.) Buch. Ham. were investigated and led to the isolation of one new limonoid named Luvunga A (1), together with seven known compounds, including one limonoid (2) and six coumarins (3-8) were isolated for the first time from the species L. scandens by various chromatography methods. Their chemical structures were elucidated by IR, UV, HR-ESI-MS, NMR 1D and 2D experiments and compared with literatures.

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

Koch, T.H.

Coumarin laser dyes upon excitation degrade to produce products that absorb at the lasing wavelength. This results in attenuation of dye laser output through interference of stimulated emission. The roles of singlet oxygen and excitation intensity on dye degradation were explored. Singlet oxygen is formed but its reactions with the dye do not appear to be a major cause of dye laser output deterioration. High light intensity results in dye-sensitized, solvent oligomerization to yield materials that interfere with dye-stimulated emission. 1, 4-Diazabicyclo2,2,2octane (DABCO)inhibits this oligomerization.

Design and synthesis of 3,3'-biscoumarin-based c-Met inhibitors.

PubMed

Xu, Jimin; Ai, Jing; Liu, Sheng; Peng, Xia; Yu, Linqian; Geng, Meiyu; Nan, Fajun

2014-06-14

A library of biscoumarin-based c-Met inhibitors was synthesized, based on optimization of 3,3'-biscoumarin hit 3, which was identified as a non-ATP competitive inhibitor of c-Met from a diverse library of coumarin derivatives. Among these compounds, 38 and 40 not only showed potent enzyme activities with IC50 values of 107 nM and 30 nM, respectively, but also inhibited c-Met phosphorylation in BaF3/TPR-Met and EBC-1 cells.

Pharmacological features of osthole.

PubMed

Jarząb, Agata; Grabarska, Aneta; Skalicka-Woźniak, Krystyna; Stepulak, Andrzej

2017-05-15

Coumarins are a group of naturally occurring compounds common in the plant world. These substances and their derivatives exhibit a broad range of biological activities. One of the naturally occurring coumarins is osthole, which can most frequently be found in plants of the Apiaceae family. Cnidium monnieri (L.) Cusson ex Juss. Angelica pubescens Maxim. and Peucedanum ostruthium (L.). It has anti-proliferative, anti-inflammatory, anti-convulsant, and antiallergic properties; apart from that, inhibition of platelet aggregation has also been proved. The impact of osthole on bone metabolism has been demonstrated; also its hepatoprotective and neuroprotective properties have been confirmed. The inhibitory effect of this metokcompound on the development of neurodegenerative diseases has been proved in experimental models. Anticancer features of osthole have been also demonstrated both in vitro on different cell lines, and in vivo using animals xenografts. Osthole inhibited proliferation, motility and invasiveness of tumor cells, which may be associated with the induction of apoptosis and cell cycle slowdown. The exact molecular mechanism of osthole anti-cancer mode of action has not been fully elucidated. A synergistic effect of osthole with other anti-tumor substances has been also reported. Modification of its chemical structure led to the synthesis of many derivatives with significant anticancer effects. To sum up, osthole is an interesting therapeutic option, due to both its direct effect on tumor cells, as well as its neuroprotective or anti-inflammatory properties. Thus, there is a chance to use osthole or its synthetic derivatives in the treatment of cancer.

Optimization of extraction conditions for osthol, a melanogenesis inhibitor from Cnidium monnieri fruits.

PubMed

Beom Kim, Seon; Kim, CheongTaek; Liu, Qing; Hee Jo, Yang; Joo Choi, Hak; Hwang, Bang Yeon; Kyum Kim, Sang; Kyeong Lee, Mi

2016-08-01

Coumarin derivatives have been reported to inhibit melanin biosynthesis. The melanogenesis inhibitory activity of osthol, a major coumarin of the fruits of Cnidium monnieri Cusson (Umbelliferae), and optimized extraction conditions for the maximum yield from the isolation of osthol from C. monnieri fruits were investigated. B16F10 melanomas were treated with osthol at concentration of 1, 3, and 10 μM for 72 h. The expression of melanogenesis genes, such as tyrosinase, TRP-1, and TRP-2 was also assessed. For optimization, extraction factors such as extraction solvent, extraction time, and sample/solvent ratio were tested and optimized for maximum yield of osthol using response surface methodology with the Box-Behnken design (BBD). Osthol inhibits melanin content in B16F10 melanoma cells with an IC50 value of 4.9 μM. The melanogenesis inhibitory activity of osthol was achieved not by direct inhibition of tyrosinase activity but by inhibiting melanogenic enzyme expressions, such as tyrosinase, TRP-1, and TRP-2. The optimal condition was obtained as a sample/solvent ratio, 1500 mg/10 ml; an extraction time 30.3 min; and a methanol concentration of 97.7%. The osthol yield under optimal conditions was found to be 15.0 mg/g dried samples, which were well matched with the predicted value of 14.9 mg/g dried samples. These results will provide useful information about optimized extraction conditions for the development of osthol as cosmetic therapeutics to reduce skin hyperpigmentation.

Rapid characterization of the chemical constituents of Cortex Fraxini by homogenate extraction followed by UHPLC coupled with Fourier transform ion cyclotron resonance mass spectrometry and GC-MS.

PubMed

Wang, Yinan; Han, Fei; Song, Aihua; Wang, Miao; Zhao, Min; Zhao, Chunjie

2016-11-01

Cortex Fraxini is an important traditional Chinese medicine. In this work, a rapid and reliable homogenate extraction method was applied for the fast extraction for Cortex Fraxini, and the method was optimized by response surface methodology. Ultra high performance liquid chromatography combined with Fourier transform ion cyclotron resonance mass spectrometry and gas chromatography with mass spectrometry were established for the separation and characterization of the constituents of Cortex Fraxini. Liquid chromatography separation was conducted on a C 18 column (150 mm × 2.1 mm, 1.8 μm), and gas chromatography separation was performed on a capillary with a 5% phenyl-methylpolysiloxane stationary phase (30 m × 0.25 mm × 0.25 mm) by injection of silylated samples. According to the results, 33 chemical compounds were characterized by liquid chromatography with mass spectrometry, and 11 chemical compounds were characterized by gas chromatography with mass spectrometry, and coumarins were the major components characterized by both gas chromatography with mass spectrometry and liquid chromatography with mass spectrometry. The proposed homogenate extraction was an efficient and rapid method, and coumarins, phenylethanoid glycosides, iridoid glycosides, phenylpropanoids, and lignans were the main constituents of Cortex Fraxini. This work laid the foundation for further study of Cortex Fraxini and will be helpful for the rapid extraction and characterization of ingredients in other traditional Chinese medicines. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Think of HIT.

PubMed

Warkentin, Theodore E

2006-01-01

Heparin-induced thrombocytopenia, or HIT, can present in many ways, ranging from common-isolated thrombocytopenia, venous thromboembolism, acute limb ischemia-to less common but specific presentations-necrotizing skin lesions at heparin injection sites, post-bolus acute systemic reactions, and adrenal hemorrhagic necrosis (secondary to adrenal vein thrombosis). Many patients with HIT have mild or moderate thrombocytopenia: the median platelet count nadir is 60 x 10(9)/L, and ranges from 15 to 150 x 10(9)/L in 90% of patients, most of whom evince a 50% or greater fall in the platelet count. HIT that begins after stopping heparin ("delayed-onset HIT") is increasingly recognized. Factors influencing risk of HIT include type of heparin (unfractionated heparin > low-molecular-weight heparin), type of patient (surgical > medical), and gender (female > male). Since timely diagnosis and treatment of HIT may reduce the risk of adverse outcomes, this review focuses on those clinical circumstances that should prompt the clinician to "think of HIT." Coumarin anticoagulants such as warfarin are ineffective in acute HIT and can even be deleterious by predisposing to micro-thrombosis via protein C depletion (venous limb gangrene and skin necrosis syndromes). Thus, it is important to avoid or postpone coumarin while managing HIT hypercoagulability, focusing on agents that inhibit thrombin directly (lepirudin, argatroban) or that inhibit its generation (danaparoid, fondaparinux). Post-marketing experience suggests that standard dosing of lepirudin is too high; current recommendations are to avoid the initial lepirudin bolus and to begin with lower infusion rates, even in patients without overt renal dysfunction.

Cyclodextrin-based star polymers as a versatile platform for nanochemotherapeutics: Enhanced entrapment and uptake of idarubicin.

PubMed

Nafee, N; Hirosue, M; Loretz, B; Wenz, G; Lehr, C-M

2015-05-01

A series of cyclodextrin-based star polymers were synthesized using β-cyclodextrin (CD) as hydrophilic core, methyl methacrylate (MMA) and tert-butyl acrylate (tBA) as hydrophobic arms. Star polymers, either homopolymers or random/block copolymers, showed narrow molecular weight distributions. Grafting hydrophobic arms created CD-based nanoparticles (CD-NPs) in the size range (130-200nm) with narrow PdI <0.15 and slightly negative ζ-potential. Particle surface could be modified with chitosan to impart a positive surface charge. Colloidal stability of CD-NPs was a function of pH as revealed by the pH-titration curves. CD-NPs were used as carrier for the chemotherapeutic drug idarubicin (encapsulation efficiency, EE ∼40%) ensuring prolonged release profile (∼80% after 48h). For cell-based studies, coumarin-6 was encapsulated as a fluorescent marker (EE ∼75%). Uptake studies carried out on A549 and Caco-2 cell lines proved the uptake of coumarin-loaded NPs as a function of time and preferential localization in the cytoplasm. Uptake kinetics revealed no saturation or plateau over 6h. Chitosan-modified NPs showed significantly improved, concentration-dependent cellular uptake. Meanwhile, CD-NPs were non-cytotoxic on both cell lines over the concentration range (0.25-3mg/ml) as studied by MTT and LDH assays. In conclusion, CD star polymers can be considered a versatile platform for a new class of biocompatible nanochemotherapy. Copyright © 2015 Elsevier B.V. All rights reserved.

Synthesis, inhibition effects and quantum chemical studies of a novel coumarin derivative on the corrosion of mild steel in a hydrochloric acid solution.

PubMed

Al-Azawi, Khalida F; Al-Baghdadi, Shaimaa B; Mohamed, Ayad Z; Al-Amiery, Ahmed A; Abed, Talib K; Mohammed, Salam A; Kadhum, Abdul Amir H; Mohamad, Abu Bakar

2016-01-01

The acid corrosion inhibition process of mild steel in 1 M HCl by 4-[(2-amino-1, 3, 4-thiadiazol-5-yl)methoxy]coumarin (ATC), has been investigated using weight loss technique and scanning electron microscopy (SEM). ATC was synthesized, and its chemical structure was elucidated and confirmed using spectroscopic techniques (infrared and nuclear magnetic resonance spectroscopy). The results indicated that inhibition efficiencies were enhanced with an increase in concentration of inhibitor and decreased with a rise in temperature. The adsorption equilibrium constant (K) and standard free energy of adsorption (ΔGads) were calculated. Quantum chemical parameters such as highest occupied molecular orbital energy, lowest unoccupied molecular orbital energy (EHOMO and ELUMO, respectively) and dipole moment (μ) were calculated and discussed. The results showed that the corrosion inhibition efficiency increased with an increase in both the EHOMO and μ values but with a decrease in the ELUMO value. Our research show that the synthesized macromolecule represents an excellent inhibitor for materials in acidic solutions. The efficiency of this macromolecule had maximum inhibition efficiency up to 96 % at 0.5 mM and diminishes with a higher temperature degree, which is revealing of chemical adsorption. An inhibitor molecule were absorbed by metal surface and follow Langmuir isotherms low and establishes an efficient macromolecule inhibitor having excellent inhibitive properties due to entity of S (sulfur) atom, N (nitrogen) atom and O (oxygen) atom.

Using experimental studies and theoretical calculations to analyze the molecular mechanism of coumarin, p-hydroxybenzoic acid, and cinnamic acid

NASA Astrophysics Data System (ADS)

Hsieh, Tiane-Jye; Su, Chia-Ching; Chen, Chung-Yi; Liou, Chyong-Huey; Lu, Li-Hwa

2005-05-01

Three natural products, Coumarin ( 1), p-hydroxybenzoic acid ( 2), trans-cinnamic acid ( 3) were isolated from the natural plant of indigenous cinnamon and the structures including relative stereochemistry were elucidated on the basis of spectroscopic data and theoretical calculations. Their sterochemical structures were determined by NMR spectroscopy, mass spectroscopy, and X-ray crystallography. The p-hydroxybenzoic acid complex with water is reported to show the existence of two hydrogen bonds. The two hydrogen bonds are formed in the water molecule of two hydrogen-accepting oxygen of carbonyl group of the p-hydroxybenzoic acid. The intermolecular interaction two hydrogen bond of the model system of the water- p-hydroxybenzoic acid was investigated. An experimental study and a theoretical analysis using the B3LYP/6-31G* method in the GAUSSIAN-03 package program were conducted on the three natural products. The theoretical results are supplemented by experimental data. Optimal geometric structures of three compounds were also determined. The calculated molecular mechanics compared quite well with those obtained from the experimental data. The ionization potentials, highest occupied molecular orbital energy, lowest unoccupied molecular orbital energy, energy gaps, heat of formation, atomization energies, and vibration frequencies of the compounds were also calculated. The results of the calculations show that three natural products are stable molecules with high reactive and various other physical properties. The study also provided an explicit understanding of the sterochemical structure and thermodynamic properties of the three natural products.

Tricyclic coumarin sulphonate derivatives with alkaline phosphatase inhibitory effects: in vitro and docking studies.

PubMed

Iqbal, Jamshed; El-Gamal, Mohammed I; Ejaz, Syeda Abida; Lecka, Joanna; Sévigny, Jean; Oh, Chang-Hyun

2018-12-01

Tissue-nonspecific alkaline phosphatase (TNAP) is an important isozyme of alkaline phosphatases, which plays different pivotal roles within the human body. Most importantly, it is responsible for maintaining the balanced ratio of phosphate and inorganic pyrophosphate, thus regulates the extracellular matrix calcification during bone formation and growth. The elevated level of TNAP has been linked to vascular calcification and end-stage renal diseases. Consequently, there is a need to search for highly potent and selective inhibitors of alkaline phosphatases (APs) for treatment of disorders associated with the over-expression of APs. Herein, a series of tricyclic coumarin sulphonate 1a-za with known antiproliferative activity, was evaluated for AP inhibition against human tissue nonspecific alkaline phosphatase (h-TNAP) and human intestinal alkaline phosphatase (h-IAP). The methylbenzenesulphonate derivative 1f (IC 50  = 0.38 ± 0.01 μM) was found to be the most active h-TNAP inhibitor. Another 4-fluorobenzenesulphonate derivative 1i (IC 50  = 0.45 ± 0.02 μM) was found as the strongest inhibitor of h-IAP. Some of the derivatives were also identified as highly selective inhibitors of APs. Detailed structure-activity relationship (SAR) was investigated to identify the functional groups responsible for the effective inhibition of AP isozymes. The study was also supported by the docking studies to rationalise the most possible binding site interactions of the identified inhibitors with the targeted enzymes.

Biotransformation of isofraxetin-6-O-β-d-glucopyranoside by Angelica sinensis (Oliv.) Diels callus.

PubMed

Zhou, Di; Zhang, Yuhua; Jiang, Zhe; Hou, Yue; Jiao, Kun; Yan, Chunyan; Li, Ning

2017-01-15

Isofraxetin-6-O-β-d-glucopyranoside, identified from traditional medicinal herbal Xanthoceras sorbifolia Bunge, has been demonstrated to be a natural neuroinflammatory inhibitor. In order to obtain more derivatives with potential anti-neuroinflammatory effects, biotransformation was carried out. According to the characteristics of coumarin skeleton, suspension cultures of Angelica sinensis (Oliv.) Diels callus (A. sinensis callus) were employed because of the presence of diverse phenylpropanoids biosynthetic enzymes. As a result, 15 products were yielded from the suspension cultures, including a new coumarin: 8'-dehydroxymethyl cleomiscosin A (1), together with 14 known compounds. Their structures were elucidated by extensive spectroscopic analysis. Furthermore, the biotransformed pathways were discussed. Among them, compound 13 was transformed from isofraxetin-6-O-β-d-glucopyranoside, while compounds 1-6, 10-12, 14-15 were derived from the culture medium stimulated by the substrate. The biotransformation processes include hydroxylation, oxidation and esterification. Furthermore, their inhibitory effects on lipopolysaccharide (LPS)-activated nitric oxide (NO) production were evaluated in BV2 microglial cells. It is worth noting that, 1, 1'-methanediylbis(4-methoxybenzene) (3), obtucarbamates A (5), 2-nonyl-4-hydroxyquinoline N-oxide (10) and 1H-indole-3-carbaldehyde (11) exhibited significant inhibitory effect against neuroinflammation with IC 50 values at 1.22, 10.57, 1.02 and 0.76μM respectively, much stronger than that of the positive control minocycline (IC 50 35.82μM). Copyright © 2016 Elsevier Ltd. All rights reserved.

Complete suppression of the fluorophore fluorescence by combined effect of multiple fluorescence quenching groups: A fluorescent sensor for Cu²⁺ with zero background signals.

PubMed

Long, Lingliang; Wu, Yanjun; Wang, Lin; Gong, Aihua; Hu, Rongfeng; Zhang, Chi

2016-02-18

The reaction-based fluorescent sensors have attracted increasing attention in the past decades. However, the application of these sensors for accurate sensing was significantly retarded by the background fluorescence from the sensors themselves. In this work, we demonstrated a novel strategy that the background fluorescence of the sensor could be completely eliminated by the combined effect of multiple fluorescence quenching groups. Based on this new strategy, as proof-of-principle study, a fluorescent sensor (CuFS) for Cu(2+) was judiciously developed. In CuFS, three types of fluorescence quenching groups were directly tethered to a commonly used coumarin fluorophore. The fluorescence of coumarin fluorophore in CuFS was completely suppressed by the combined effect of these fluorescence quenching groups. Upon treatment with 22 μM Cu(2+), sensor CuFS achieved a dramatic fluorescence enhancement (fluorescence intensity enhanced up to 811-fold) centered at 469 nm. The detection limits was determined to be 12.3 nM. The fluorescence intensity enhancement also showed a good linearity with the Cu(2+) concentration in the range of 12.3 nM to 2 μM. By fabricating test strips, sensor CuFS can be utilized as a simple tool to detect Cu(2+) in water samples. Furthermore, the fluorescent sensor was successfully applied in detecting different concentration of Cu(2+) in living cells. Copyright © 2015 Elsevier B.V. All rights reserved.

Photoinduced electron transfer across a molecular wall: coumarin dyes as donors and methyl viologen and TiO2 as acceptors.

PubMed

Porel, Mintu; Klimczak, Agnieszka; Freitag, Marina; Galoppini, Elena; Ramamurthy, V

2012-02-21

Coumarins C-153, C-480, and C-1 formed 1:2 (guest:host) complexes with a water-soluble cavitand having eight carboxylic acid groups (OA) in aqueous borate buffer solution. The complexes were photoexcited in the presence of electron acceptors (methyl viologen, MV(2+), or TiO(2)) to probe the possibility of electron transfer between a donor and an acceptor physically separated by a molecular wall. In solution at basic pH, the dication MV(2+) was associated to the exterior of the complex C-153@OA(2), as suggested by diffusion constants (~1.2 × 10(-6) cm(2)/s) determined by DOSY NMR. The fluorescence of C-153@OA(2) was quenched in the presence of increasing amounts of MV(2+) and Stern-Volmer plots of I(o)/I and τ(o)/τ vs [MV(2+)] indicated that the quenching was static. As per FT-IR-ATR spectra, the capsule C-153@OA(2) was bound to TiO(2) nanoparticle films. Selective excitation (λ(exc) = 420) of the above bound complex resulted in fluorescence quenching. When adsorbed on insulating ZrO(2) nanoparticle films, excitation of the complex resulted in a broad fluorescence spectrum centered at 500 nm and consistent with C-153 being within the lipophilic capsule interior. Consistent with the above results, colloidal TiO(2) quenched the emission while colloidal ZrO(2) did not.

Cytochrome P450-mediated warfarin metabolic ability is not a critical determinant of warfarin sensitivity in avian species: In vitro assays in several birds and in vivo assays in chicken.

PubMed

Watanabe, Kensuke P; Kawata, Minami; Ikenaka, Yoshinori; Nakayama, Shouta M M; Ishii, Chihiro; Darwish, Wageh Sobhi; Saengtienchai, Aksorn; Mizukawa, Hazuki; Ishizuka, Mayumi

2015-10-01

Coumarin-derivative anticoagulant rodenticides used for rodent control are posing a serious risk to wild bird populations. For warfarin, a classic coumarin derivative, chickens have a high median lethal dose (LD50), whereas mammalian species generally have much lower LD50. Large interspecies differences in sensitivity to warfarin are to be expected. The authors previously reported substantial differences in warfarin metabolism among avian species; however, the actual in vivo pharmacokinetics have yet to be elucidated, even in the chicken. In the present study, the authors sought to provide an in-depth characterization of warfarin metabolism in birds using in vivo and in vitro approaches. A kinetic analysis of warfarin metabolism was performed using liver microsomes of 4 avian species, and the metabolic abilities of the chicken and crow were much higher in comparison with those of the mallard and ostrich. Analysis of in vivo metabolites from chickens showed that excretions predominantly consisted of 4'-hydroxywarfarin, which was consistent with the in vitro results. Pharmacokinetic analysis suggested that chickens have an unexpectedly long half-life despite showing high metabolic ability in vitro. The results suggest that the half-life of warfarin in other bird species could be longer than that in the chicken and that warfarin metabolism may not be a critical determinant of species differences with respect to warfarin sensitivity. © 2015 SETAC.

Ceylon cinnamon does not affect postprandial plasma glucose or insulin in subjects with impaired glucose tolerance.

PubMed

Wickenberg, Jennie; Lindstedt, Sandra; Berntorp, Kerstin; Nilsson, Jan; Hlebowicz, Joanna

2012-06-01

Previous studies on healthy subjects have shown that the intake of 6 g Cinnamomum cassia reduces postprandial glucose and that the intake of 3 g C. cassia reduces insulin response, without affecting postprandial glucose concentrations. Coumarin, which may damage the liver, is present in C. cassia, but not in Cinnamomum zeylanicum. The aim of the present study was to study the effect of C. zeylanicum on postprandial concentrations of plasma glucose, insulin, glycaemic index (GI) and insulinaemic index (GII) in subjects with impaired glucose tolerance (IGT). A total of ten subjects with IGT were assessed in a crossover trial. A standard 75 g oral glucose tolerance test (OGTT) was administered together with placebo or C. zeylanicum capsules. Finger-prick capillary blood samples were taken for glucose measurements and venous blood for insulin measurements, before and at 15, 30, 45, 60, 90, 120, 150 and 180 min after the start of the OGTT. The ingestion of 6 g C. zeylanicum had no significant effect on glucose level, insulin response, GI or GII. Ingestion of C. zeylanicum does not affect postprandial plasma glucose or insulin levels in human subjects. The Federal Institute for Risk Assessment in Europe has suggested the replacement of C. cassia by C. zeylanicum or the use of aqueous extracts of C. cassia to lower coumarin exposure. However, the positive effects seen with C. cassia in subjects with poor glycaemic control would then be lost.

Effect of a total extract from Fraxinus ornus stem bark and esculin on zymosan- and carrageenan-induced paw oedema in mice.

PubMed

Stefanova, Z; Neychev, H; Ivanovska, N; Kostova, I

1995-05-01

This study investigates the total ethanol extract (TE) of the stem bark of Fraxinus ornus and its constituent esculin (EN). They inhibited classical pathway (CP) and alternative pathway (AP) of complement activation in mouse serum. After intraperitoneal administration the total extract displayed antiinflammatory activity in both zymosan- and carrageenan-induced paw oedema in mice. The results suggest that the traditional use of Fraxinus ornus stem bark extracts in the treatment of inflammatory disorders is at least partially due to its coumarin constituents.

Ethyl 4-(2-fur-yl)-2-oxochroman-3-carboxyl-ate.

PubMed

Prabhakar, Maddela; Reddy, J S N; Kumar, N Ravi; Ganesh, S Viswanadha; Solomon, K Anand

2010-05-12

The title compound, C(16)H(14)O(5), was prepared from the reaction of 3-carbethoxy-coumarin with furan in the presence of AlCl(3) as catalyst. In the crystal, inter-molecular C-H⋯O hydrogen-bonding inter-actions between four mol-ecules lead to a tetra-mer in the unit cell. The furan ring is anti-periplanar [C-C-C-O = 167.9 (13)°] and the ethoxy-carbonyl group is (-)anti-clinal [C-C-C-O = -128.6 (14)°] to the lactone ring.

A new strategy to construct a FRET platform for ratiometric sensing of hydrogen sulfide.

PubMed

He, Longwei; Lin, Weiying; Xu, Qiuyan; Wei, Haipeng

2015-01-28

We introduce a new FRET strategy to construct a ratiometric fluorescent H2S sensor. The ratio emission signal of the coumarin-naphthalimide dyad is modulated by the FRET process, which works in coordination with the ICT mechanism. The FRET process on/off is controlled through tuning the overlap level of the donor emission spectrum with the acceptor absorption via modulation of the acceptor fluorophore absorption wavelength. was applied to visualize both the intracellular exogenous and endogenous H2S through blue and green emission channels.

[Advances in the pharmacological study of Morus alba L].

PubMed

Yang, Shuang; Wang, Bao-Lian; Li, Yan

2014-06-01

Morus alba L. (mulberry) is a well-known deciduous tree, belonging to the genus of Morus of Moraceae famlily. Its leaves, twigs, roots (bark) and fruits are widely used in the traditional Chinese medicine. The active constituents of mulberry contained flavonoids, alkaloids, steroids, coumarins, with the significant hypoglycemic, hypolipidemic, antihypertension, anti-oxidation, anti-inflammatory, anti-bacterial, anti-tumor and immunomodulatory activities. This review summarized the research progress of the major pharmacological activity, pharmacokinetics and drug-drug interaction based on CYPs and transporters of mulberry and its active constituents.

Isolation of furocoumarins from bergamot fruits as HL-60 differentiation-inducing compounds.

PubMed

Kawaii, S; Tomono, Y; Katase, E; Ogawa, K; Yano, M

1999-10-01

The HL-60 differentiation-inducing compounds in bergamot fruits were isolated with column chromatography and identified as bergamottin, bergapten, and citropten by (1)H and (13)C NMR. Their HL-60 differentiation-inducing activity was measured by examining nitro blue tetrazolium (NBT) reducing, nonspecific acid esterase (NSE), specific esterase (SE), and phagocytic activities, and bergamottin showed the strongest activity among the coumarins isolated from bergamot fruits. The structure-activity relationship obtained from HL-60 differentiation assay suggests that hydrophobicity of furocoumarins is correlated with their activity.

Cytotoxic constituents of ethyl acetate fraction from Dianthus superbus.

PubMed

Ding, Chengli; Zhang, Wu; Li, Jie; Lei, Jiachuan; Yu, Jianqing

2013-01-01

The ethyl acetate fraction (EE-DS) from Dianthus superbus was found to possess the cytotoxic activity against cancer cells in previous study. To investigate cytotoxic constituents, the bioassay-guided isolation of compounds from EE-DS was performed. Two dianthramides (1 and 2), three flavonoids (3-5), two coumarins (6 and 7) and three other compounds (8-10) were obtained. Structures of isolated compounds were identified by spectroscopic analysis. Cytotoxicity of the compounds against HepG2 cells was evaluated. Compound 1 showed the strongest cytotoxicity, compounds 10, 4, 3 and 5 had moderate cytotoxicity.

Recognition of Mg²⁺ by a new fluorescent "turn-on" chemosensor based on pyridyl-hydrazono-coumarin.

PubMed

Orrego-Hernández, Jessica; Nuñez-Dallos, Nelson; Portilla, Jaime

2016-05-15

A new fluoroionophore PyHC bearing 2-pyridylhydrazone and 7-hydroxycoumarin moieties for selective detection of Mg(2+) was synthesized and characterized. This chemosensor exhibited "turn-on" fluorescence behavior and was sensitive to Mg(2+) concentrations as low as 105 nmol L(-1) in ethanol-water solution. Detailed spectroscopic studies revealed the binding mode of a 1:1 complex between PyHC and Mg(2+) that leads to a fluorescence enhancement. Copyright © 2016 Elsevier B.V. All rights reserved.

Effects of Solvation On One- and Two-Photon Spectra of Coumarin Derivatives: A TDDFT Study (Preprint)

DTIC Science & Technology

2006-10-01

1999,103,9614. (14) Pal, H.; Nad, S.; Kumbhakar, M. J Chern. Phys. 2003, 119,443. (15) Barik , A.; Nath, S.; Pal, H. J Chern. Phys. 2003, 119, 10202...Signature// TIM J . SCHUMACHER, Chief Survivability and Sensor Materials Division This report is published in the interest of...6-311 ++G(d,p) and the aug-cc-pVTZ basis sets. Theory Expt System/Method E(S])f Jlo]Energy (JlO]) [ j ]Solvent C120 CAMB3LYP 4.29 (4.24)0.373 (0.368

Anti-complementary constituents of Houttuynia cordata and their targets in complement activation cascade.

PubMed

Jiang, Yun; Lu, Yan; Zhang, Yun-Yi; Chen, Dao-Feng

2014-01-01

Activity-guided fractionation for complement inhibitors led to the isolation of 23 known compounds from Houttuynia cordata Thunb. Seven flavonoids, two alkaloids, one coumarin and two phenols showed anti-complementary activity. Preliminary inhibitory mechanism of four flavonoids, including quercitrin, afzelin, isoquercitrin and quercetin in the complement activation cascade were examined for the first time. The results indicated that the target components of flavonols are different from those of flavonosides, and the glycoside moieties may be necessary to block C3 and C4 components.

Efficient 7-J flashlamp-pumped dye laser at 500-nm wavelength

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

Everett, P.N.; Aldag, H.R.; Ehrlich, J.J.

1986-07-01

An existing transverse flow flashlamp-pumped dye laser capable of operation at 500 pps for extended periods of time has been modified and optimized for operation at 502 nm using coumarin 504. Energies of over 7 J/ pulse and efficiencies of over 1% have been demonstrated in single-shot operation. This has been achieved by using a spectral transfer dye in the flashlamp coolant to increase the useful output of the flashlamps. Flashlamps were tested at up to 400-J input per lamp for extended periods to develop lamp life data.

Warfarin interaction with Matricaria chamomilla

PubMed Central

Segal, Robert; Pilote, Louise

2006-01-01

No cases have been reported of Matricaria chamomilla potentiating the effects of warfarin. Nevertheless there is a theoretical risk for potentiation, since the herb is thought to be a coumarin constituent. We describe the case of a 70-year-old woman who, while being treated with warfarin, was admitted to hospital with multiple internal hemorrhages after having used chamomile products (tea and body lotion) to soothe upper respiratory tract symptoms. Patient education on the potential risk of taking chamomile products while being treated with warfarin is necessary to avoid such occurrences. PMID:16636327

A colorimetric turn-on optical chemosensor for Cu2+ ions and its application as solid state sensor

NASA Astrophysics Data System (ADS)

Pannipara, Mehboobali; Al-Sehemi, Abdullah G.; Assiri, Mohammed; Kalam, Abul

2018-05-01

We report a novel coumarin based optical chemosensor (Probe 1) for the selective and sensitive detection of Cu2+ ions in aqueous medium. The addition of Cu2+ ions to Probe 1 shows distinct color change from light yellow to pinkish red color under visible light with the sensing limit of 1.54 μM. Moreover, practical utility of Probe 1 as solid state optical sensor (test paper, TLC plates) for sensing Cu2+ has been demonstrated by instantaneous "naked eye" response.

Water-soluble constituents of the root barks of Fraxinus rhynchophylla (Chinese drug Qinpi).

PubMed

Xiao, Kai; Song, Qing-Hong; Zhang, Shu-Wei; Xuan, Li-Jiang

2008-01-01

Chemical studies on the roots of Fraxinus rhynchophylla led to the isolation of fraxisecoside (1), a novel coumarin-secoiridoid hybrid glycoside, namely, fraxetin-8-O-[11'-methyl-oleosidyl-(7'-->6'')]-beta-D-glucopyranoside and 14 known compounds. Their structures were elucidated based on chemical evidence and spectroscopic analysis, including extensive 2D NMR methods. Compound 2 was first isolated as a pure compound. Compound 1 exhibited moderate PTP1B inhibition activity. Compounds 1 and 2 showed inhibition activity against B- and T-cell proliferation, without cytotoxicity.

Coumarins from the roots of Angelica dahurica cause anti-allergic inflammation

PubMed Central

Li, Dong; Wu, Li

2017-01-01

Allergic inflammation is induced by allergens and leads to various allergic diseases, including rhinitis, asthma and conjunctivitis. Histamine is important in the pathogenesis of an immunoglobulin E-dependent allergic reaction and results in the secretion of cytokines associated with inflammation. Angelica dahurica (A. dahurica) is a medicinal plant widely used in China for the treatment of symptoms related to allergic inflammation. The present study investigated the chemical constituents from A. dahurica and evaluated their reductive effect on allergic inflammation. As a result, 15 compounds including 13 coumarins have been identified as isoimperatorin (1), imperatorin (2), oxypeucedanin (3), oxypeucedanin hydrate (4), bergapten (5), byakangelicin (6), phellopterin (7), byakangelicol (8), isopimpinellin (9), xanthotoxol (10), xanthotoxin (11), pimpinellin (12), scopoletin (13), β-sitosterol (14) and daucosterol (15). Compounds 1–13 were able to reduce the release of histamine, with compounds 4–6 exhibiting the most potent activity. Furthermore, compounds 1–12 were able to inhibit the secretion of tumor necrosis factor-α, interleukin (IL)-1β and IL-4, with compounds 5 and 7 exhibiting the strongest inhibitory effects. These compounds implemented the inhibitory effects on the expression of inflammatory cytokine genes through the inhibition of nuclear factor-κB activation. Virtual screening by a docking program indicated that compound 3 is a potent histamine H1 receptor antagonist. Additionally, the calculated physicochemical properties of these compounds support most furanocoumarins to be delivered to binding sites and permeate the cell membrane. The present findings contribute to understanding how A. dahurica attenuates allergic inflammation. PMID:28673013

Antioxidant and antiradical properties of esculin, and its effect in a model of epirubicin-induced bone marrow toxicity.

PubMed

Biljali, Sefedin; Hadjimitova, Vera A; Topashka-Ancheva, Margarita N; Momekova, Denitsa B; Traykov, Trayko T; Karaivanova, Margarita H

2012-01-01

To evaluate the effect of esculin, a plant coumarin glucoside, on free radicals and against epirubicin-induced toxicity on bone marrow cells. Antioxidant activity was assessed by a luminol-dependent chemiluminescence method or NBT test in a xanthine-xanthine oxidase system, and two iron-dependent lipid peroxidation systems. In vivo experiments were carried out in epirubicin-treated mice, alone or in a combination with esculin. Genotoxicity of the anthracycline drug was assessed by cytogenetic analysis and an autoradiographic assay. Esculin inactivated superoxide anion radicals in both systems we used. It exerted SOD-mimetic effect and reduced the level of superoxide radicals generated in a xanthine-xanthine oxidase system by 30%. Esculin also showed an antioxidant effect in a model of Fe2+-induced lipid peroxidation. Cytogenetic analysis showed that epirubicin had a marked influence on the structure of metaphase chromosomes of normal bone marrow cells. Inclusion of esculin in the treatment protocol failed to ameliorate the epirubicin-induced antiproliferative effects and genotoxicity in bone marrow cells. In this study the ability of the coumarin glucoside esculin to scavenge superoxide radicals and to decrease Fe-induced lipid peroxidation was documented. However, despite the registered antioxidant effects the tested compound failed to exert cytoprotection in models of anthracycline-induced genotoxicity in bone marrow cells. The results of this study warrant for more precise further evaluation of esculin, employing different test systems and end-points and a wider range of doses to more precisely appraise its potential role as a chemoprotective/resque agent.

Studies on the solvation dynamics of coumarin 153 in 1-ethyl-3-methylimidazolium alkylsulfate ionic liquids: dependence on alkyl chain length.

PubMed

Das, Sudhir Kumar; Sarkar, Moloy

2012-08-06

Steady-state and time-resolved fluorescence behavior of coumarin 153 (C153) is investigated in a series of 1-ethyl-3-methylimidazolium alkylsulfate ([C(2)mim][C(n)OSO(3)]) ionic liquids differing only in the length of the linear alkyl chain (n = 4, 6, and 8) in the anion. The aim of the present study is to understand the role of alkyl chain length in solute rotation and solvation dynamics of C153 in these ionic liquids. The blueshift observed in the steady-state absorption and emission maxima of C153 on going from the C(4)OSO(3) to the C(8)OSO(3) system indicates increasing nonpolar character of the microenvironment of the solute with increasing length of the alkyl side chain of the anion of the ionic liquids. The average solvation time is also found to increase on changing the substituent from butyl to octyl, and this is attributed to the increase in the bulk viscosity of the ILs. A steady blueshift of the time-zero maximum of the fluorescence spectrum with increasing alkyl chain length also indicates that the probe molecule experiences a less polar environment in the early part of the dynamics. Rotational dynamics of C153 are also analyzed by using the Stokes-Einstein-Debye (SED), Gierer-Wirtz (GW), and Dote-Kivelson-Schwartz (DKS) theories. Analyses of the results seem to suggest decoupling of the rotational motion of the probe from solvent viscosity. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

RGD-modified pH-sensitive liposomes for docetaxel tumor targeting.

PubMed

Chang, Minglu; Lu, Shanshan; Zhang, Fang; Zuo, Tiantian; Guan, Yuanyuan; Wei, Ting; Shao, Wei; Lin, Guimei

2015-05-01

Phosphatidylethanolamine-based pH-sensitive liposomes of various compositions have been described as efficient systems for delivery of therapeutic molecules into tumor cells. The aim of this work was to develop a drug delivery system based on pH-sensitive liposomes (PLPs) that were modified with arginine-glycine-aspartic acid (RGD) peptide to enhance the effectiveness of docetaxel treatment. Docetaxel/coumarin-6 loaded PLPs were prepared by the thin-film dispersion method and characterized in detail, including by particle size, polydispersity, zeta potential and drug encapsulation efficiency. In vitro studies using MCF-7, HepG2and A549 cells were employed to investigate cytotoxicity and cellular uptake of the drug solution or docetaxel/coumarin-6 loaded PLPs. The accumulation of 7-nitro-2-1,3-benzoxadiazol-4-yl (NBD)-labeled liposomes in vivo was studied through tumor section imaging of xenograft mouse models of MCF-7 24h after intravenous administration. The particle size of the non-coated or RGD modified PLPs ranged between 146 and 129nm. Drug release in vitro was modestly prolonged and had good pH sensitivity. In the in vitro study, RGD-coated PLPs showed higher cytotoxicity and cellular uptake relative to non-coated ones. The results of the in vivo study showed that RGD-coated PLPs had higher fluorescence, which suggested a more efficient accumulation than normal PLPs in tumors. In conclusion, these results confirmed RGD-modified PLPs as a potential drug delivery system to achieve controlled release and tumor targeting. Copyright © 2015 Elsevier B.V. All rights reserved.

Isofraxidin, a coumarin component improves high-fat diet induced hepatic lipid homeostasis disorder and macrophage inflammation in mice.

PubMed

Li, Jian; Li, Xiaofei; Li, Zhike; Zhang, Lu; Liu, Yonggang; Ding, Hong; Yin, Shanye

2017-08-01

Isofraxidin (IF) is a coumarin compound produced in the functional foods Siberian ginseng and Apium graveolens. The first objective of this study was to investigate the protective effects and putative methods of IF in combating lipotoxicity in vitro and in vivo. Oleic acid was used to induce lipid turbulence in human hepatoma cells (HepG2). Alterations in triglyceride metabolism, inflammation and oxidative status were monitored. Results show that IF mainly reduced triglyceride accumulation, TNF-α release and ROS activation in metabolic disordered cells. Next, a high-fat diet, which induced a non-alcoholic fatty liver disease, was used to evaluate the therapeutic action of IF. Our results show that treatment with IF significantly inhibited the high-fat diet-induced elevation in body weight, liver weight, lipid metabolism (TG, TC and HDL-C) and hepatic injury in mice. In biochemical terms, treatment with IF resulted in enhanced phosphorylation of AMPKα and ACC, as well as reduced hepatic expression of FAS and HMGC, suggesting that lipogenesis was compromised. We also found robust evidence that treatment with IF significantly depleted infiltrating inflammatory cells (F4/80 + Kupffer cells and CD68 + macrophages) and inflammatory cytokine release (TNFα and IL-6). Moreover, the anti-inflammatory activity in IF-treated hepatic tissue correlated with down-regulation of TLR4 expression and NF-κB transcription. In sum, these results suggest that IF might play a protective role against lipid metabolism disorder induced by a high-fat diet via inhibition of lipid production and inflammation in the liver.

Simultaneous quantification and identification of flavonoids, lignans, coumarin and amides in leaves of Zanthoxylum armatum using UPLC-DAD-ESI-QTOF-MS/MS.

PubMed

Bhatt, Vinod; Sharma, Sushila; Kumar, Neeraj; Sharma, Upendra; Singh, Bikram

2017-01-05

The current study presents isolation and characterization of twelve compounds including catechin (1), isovitexin (2), hesperidin (3), psoralin (4), eudesmin (5), kobusin (6), fargesin (7), sesamin (8), asarinin (9), planispine-A (10), α-sanshool (11) and vitexin (12), from the leaves of Zanthoxylum armatum. Further, two rapid and simple ultra performance liquid chromatography-diode array detection (UPLC-DAD) methods were developed for the simultaneous quantitative determination of isolated compounds from Z. armatum leaves. These analytical methods were validated for linearity, precision, accuracy, limit of detection (LOD) and limit of quantification (LOQ). The LOD and LOQ were in the range of 0.06-0.21μg/mL and 0.19-0.69μg/mL, respectively. The validated method was linear (R 2 ≥0.9906), precise in terms of peak area (intra-day RSDs <3.8% and inter-day RSDs <2.7%), and accurate (109.6-92.5%). This is the first report on the isolation and quantification of 1, 2, 4 and 12 in Z. armatum and 3 in Zanthoxylum genus. The methods: were successfully applied to assess the quality of samples collected from different locations of Himachal Pradesh during summer and winter season. The results demonstrated that flavonoids and furofuran lignans were the major constituents in Z. armatum leaves. The developed methods: were further applied for tandem electrospray ionization-mass spectrometry (UPLC-DAD-ESI-MS/MS) and total eighteen compounds were identified including phenolic acid, flavonoids, furofuran lignans, coumarin and isobutyl amides. Copyright © 2016 Elsevier B.V. All rights reserved.

F420H2-Dependent Degradation of Aflatoxin and other Furanocoumarins Is Widespread throughout the Actinomycetales

PubMed Central

Lapalikar, Gauri V.; Taylor, Matthew C.; Warden, Andrew C.; Scott, Colin; Russell, Robyn J.; Oakeshott, John G.

2012-01-01

Two classes of F420-dependent reductases (FDR-A and FDR-B) that can reduce aflatoxins and thereby degrade them have previously been isolated from Mycobacterium smegmatis. One class, the FDR-A enzymes, has up to 100 times more activity than the other. F420 is a cofactor with a low reduction potential that is largely confined to the Actinomycetales and some Archaea and Proteobacteria. We have heterologously expressed ten FDR-A enzymes from diverse Actinomycetales, finding that nine can also use F420H2 to reduce aflatoxin. Thus FDR-As may be responsible for the previously observed degradation of aflatoxin in other Actinomycetales. The one FDR-A enzyme that we found not to reduce aflatoxin belonged to a distinct clade (herein denoted FDR-AA), and our subsequent expression and analysis of seven other FDR-AAs from M. smegmatis found that none could reduce aflatoxin. Certain FDR-A and FDR-B enzymes that could reduce aflatoxin also showed activity with coumarin and three furanocoumarins (angelicin, 8-methoxysporalen and imperatorin), but none of the FDR-AAs tested showed any of these activities. The shared feature of the compounds that were substrates was an α,β-unsaturated lactone moiety. This moiety occurs in a wide variety of otherwise recalcitrant xenobiotics and antibiotics, so the FDR-As and FDR-Bs may have evolved to harness the reducing power of F420 to metabolise such compounds. Mass spectrometry on the products of the FDR-catalyzed reduction of coumarin and the other furanocoumarins shows their spontaneous hydrolysis to multiple products. PMID:22383957

F420H2-dependent degradation of aflatoxin and other furanocoumarins is widespread throughout the actinomycetales.

PubMed

Lapalikar, Gauri V; Taylor, Matthew C; Warden, Andrew C; Scott, Colin; Russell, Robyn J; Oakeshott, John G

2012-01-01

Two classes of F(420)-dependent reductases (FDR-A and FDR-B) that can reduce aflatoxins and thereby degrade them have previously been isolated from Mycobacterium smegmatis. One class, the FDR-A enzymes, has up to 100 times more activity than the other. F(420) is a cofactor with a low reduction potential that is largely confined to the Actinomycetales and some Archaea and Proteobacteria. We have heterologously expressed ten FDR-A enzymes from diverse Actinomycetales, finding that nine can also use F(420)H(2) to reduce aflatoxin. Thus FDR-As may be responsible for the previously observed degradation of aflatoxin in other Actinomycetales. The one FDR-A enzyme that we found not to reduce aflatoxin belonged to a distinct clade (herein denoted FDR-AA), and our subsequent expression and analysis of seven other FDR-AAs from M. smegmatis found that none could reduce aflatoxin. Certain FDR-A and FDR-B enzymes that could reduce aflatoxin also showed activity with coumarin and three furanocoumarins (angelicin, 8-methoxysporalen and imperatorin), but none of the FDR-AAs tested showed any of these activities. The shared feature of the compounds that were substrates was an α,β-unsaturated lactone moiety. This moiety occurs in a wide variety of otherwise recalcitrant xenobiotics and antibiotics, so the FDR-As and FDR-Bs may have evolved to harness the reducing power of F(420) to metabolise such compounds. Mass spectrometry on the products of the FDR-catalyzed reduction of coumarin and the other furanocoumarins shows their spontaneous hydrolysis to multiple products.

Analysis of Yersinia enterocolitica Effector Translocation into Host Cells Using Beta-lactamase Effector Fusions.

PubMed

Wolters, Manuel; Zobiak, Bernd; Nauth, Theresa; Aepfelbacher, Martin

2015-10-13

Many gram-negative bacteria including pathogenic Yersinia spp. employ type III secretion systems to translocate effector proteins into eukaryotic target cells. Inside the host cell the effector proteins manipulate cellular functions to the benefit of the bacteria. To better understand the control of type III secretion during host cell interaction, sensitive and accurate assays to measure translocation are required. We here describe the application of an assay based on the fusion of a Yersinia enterocolitica effector protein fragment (Yersinia outer protein; YopE) with TEM-1 beta-lactamase for quantitative analysis of translocation. The assay relies on cleavage of a cell permeant FRET dye (CCF4/AM) by translocated beta-lactamase fusion. After cleavage of the cephalosporin core of CCF4 by the beta-lactamase, FRET from coumarin to fluorescein is disrupted and excitation of the coumarin moiety leads to blue fluorescence emission. Different applications of this method have been described in the literature highlighting its versatility. The method allows for analysis of translocation in vitro and also in in vivo, e.g., in a mouse model. Detection of the fluorescence signals can be performed using plate readers, FACS analysis or fluorescence microscopy. In the setup described here, in vitro translocation of effector fusions into HeLa cells by different Yersinia mutants is monitored by laser scanning microscopy. Recording intracellular conversion of the FRET reporter by the beta-lactamase effector fusion in real-time provides robust quantitative results. We here show exemplary data, demonstrating increased translocation by a Y. enterocolitica YopE mutant compared to the wild type strain.

Monitoring of nanoclay-protein adsorption isotherms via fluorescence techniques.

PubMed

Felbeck, Tom; Moss, Sebastian; Botas, Alexandre M P; Lezhnina, Marina M; Ferreira, Rute A S; Carlos, Luís D; Kynast, Ulrich H

2017-09-01

The investigation of nanoparticles and their interaction with bio-macromolecules have become an important issue; the widely discussed protein corona around nanoparticles and their biological fate in general have drawn particular attention. Here, we focus on nanoclay dispersions and the use of solvatochromic fluorescent dyes (Dansyl and Coumarin 153) for monitoring the interaction with two model proteins, bovine serum albumin and β-lactoglobulin. On one hand, these dyes are poorly emissive in water, but experience a boost in their fluorescence when adsorbed into the hydrophobic domains of proteins. On the other hand, (nano)clays and clay minerals have previously been investigated in terms of their individual protein adsorption isotherms and their usefulness for the solubilization of water-insoluble dyes into an aqueous environment. In the following, we have combined all three individual parts (nanoclay, fluorophore and protein) in dispersions in a wide range of concentration ratios to systematically study the various adsorption processes via fluorescence techniques. In order to clarify the extent of dye diffusion and adsorption-desorption equilibria in the investigations, nanoclay hybrids with an adsorbed dye (Coumarin 153) and a covalently conjugated dye (Dansyl) were compared. The results suggest that the fluorescence progression of protein titration curves correlate with the amount of protein adsorbed, matching their reported adsorption isotherms on hectorite clays. Furthermore, experimental data on the protein monolayer formation around the nanoclays could be extracted due to only minor alterations of the dispersions' optical quality and transparency. In this manner, a fluorescence-based monitor for the formation of the globular protein layer around the nanoclay was realized. Copyright © 2017 Elsevier B.V. All rights reserved.

Antihypertensive effect of auraptene, a monoterpene coumarin from the genus Citrus, upon chronic administration

PubMed Central

Razavi, Bibi Marjan; Arasteh, Ebrahim; Imenshahidi, Mohsen; Iranshahi, Mehrdad

2015-01-01

Objective(s): Auraptene, a monoterpene coumarin from Citrus species, exhibits cardioprotective effects. In this study, the effects of auraptene administration were investigated on blood pressure of normotensive and desoxycorticosterone acetate (DOCA) salt induced hypertensive rats. Materials and Methods: Five weeks administration of auraptene (2, 4, 8 and 16 mg/kg/day) and nifedipine (0.25, 0.5, 1, 2 and 4 mg/kg/day) in different groups of normotensive and hypertensive rats (at the end of 3 weeks treatment by DOCA salt) was carried out and their effects on mean systolic blood pressure (MSBP) and mean heart rate (MHR) were evaluated using tail cuff method. Results: Our results indicated that chronic administration of auraptene (2, 4, 8 and 16 mg/kg/day) significantly reduced the MSBP in DOCA salt treated rats in a dose and time dependent manner. The percent of decreases in MSBP levels by the highest dose of auraptene (16 mg/kg) at the end of 4 th to 8 th weeks, were 7.00%, 10.78%, 16.07%, 21.28% and 27.54% respectively (P<0.001). Moreover the antihypertensive effect of auraptene was less than nifedipine (ED50 value of nifedipine = 0.7 mg/kg at 8th week and ED50 value of auraptene = 5.64 mg/kg at 8 week). Conclusion: Auraptene considerably reduced MSBP in hypertensive rats, but not in normotensive (normal saline treated) rats. The results of MHR measurement showed that the increase in MHR was not significant in comparison with DOCA treated rats. PMID:25810889

Decursinol and decursin protect primary cultured rat cortical cells from glutamate-induced neurotoxicity.

PubMed

Kang, So Young; Kim, Young Choong

2007-06-01

We previously reported six neuroprotective decursinol derivatives, coumarins from Angelica gigas (Umbelliferae) roots. To elucidate the action patterns of decursinol derivatives, we investigated the neuroprotective effects of decursinol and decursin, which showed highly significant activity and were major constituents of A. gigas, using primary cultures of rat cortical cells in-vitro. At concentrations of 0.1-10.0 microM, both decursinol and decursin exerted a significant neuroprotective activity pretreatment and throughout treatment. In addition, decursin had a neuroprotective impact in the post-treatment paradigm implying that decursin might possess different action mechanisms from that of decursinol in the protection of neurons against glutamate injury. Both decursinol and decursin effectively reduced the glutamate-induced increased intracellular calcium ([Ca(2+)](i)) in cortical cells, suggesting that these two coumarins may exert neuroprotection by reducing calcium influx by overactivation of glutamate receptors. This suggestion was supported by the result that decursinol and decursin protected neurons against kainic acid (KA)-induced neurotoxicity better than against that induced by N-methyl-D-aspartate (NMDA). Moreover, both decursinol and decursin significantly prevented glutamate-induced decreases in glutathione, a cellular antioxidant, and glutathione peroxidase activity. In addition, both compounds efficiently reduced the overproduction of cellular peroxide in glutamate-injured cortical cells. These results suggested that both decursinol and decursin protected primary cultured rat cortical cells against glutamate-induced oxidative stress by both reducing calcium influx and acting on the cellular antioxidative defence system. Moreover, decursin is considered to probably have a different action mechanism from that of decursinol in protecting cortical cells against glutamate injury.

Application of bacterial reverse mutation assay for detection of non-genotoxic carcinogens.

PubMed

Kanode, Rewan; Chandra, Saurabh; Sharma, Sharad

2017-06-01

Non-genotoxic carcinogens may play a significant role in development of cancer. Currently short-term assays for mutagenicity classify genotoxic carcinogens and lack the abilities to detect epigenetic carcinogens. The need to develop an endpoint always remains to recognize potentially carcinogenic agents employing rapid and practical bioassays. For this, the present study utilized TA98 and TA1537 tester strains of Salmonella typhimurium to evaluate four non-genotoxic carcinogenic agents (Coumarin, β-Myrcene, Bis(2-ethylhexyl) phthalate and trans-anethole). These chemicals were tested individually and in combination with promutagens 2-aminoanthracene (2AA) and benzo(a)pyrene (BP) in presence of metabolic activation system (S9) by plate incorporation method. Exposure to all four test chemicals revealed marked increase of revertant colonies in promutagen combined groups as compared to promutagens alone. However significantly greater fold responses were observed with 2AA combination groups (Coumarin +2AA, β-Myrcene +2AA, Bis(2-ethylhexyl) phthalate +2AA and trans-anethole +2AA) with TA98 strain as compared with TA1537, which seems to have enhanced the mutagenic response of 2AA in metabolically activated conditions. It is concluded that out of both tester strains TA98 strain of Salmonella typhimurium has the potential to detect non-genotoxic carcinogens when combined with potent promutgens either by inhibiting or modulating activities of liver microsomal enzymes biochemically which may indirectly contribute to neoplastic alterations. Further this simple, short-term alternative assay may provide rapid information during extrapolative toxicology for differentiating genotoxic and non-genotoxic carcinogens.

Synthesis, Photophysical and Computational Study of Novel Coumarin-based Organic Dyes.

PubMed

Kumbar, Mahadev N; Sannaikar, Madivalagouda S; Shaikh, Saba Kauser J; Kamble, Atulkumar A; Wari, Manjunath N; Inamdar, Sanjeev R; Qiao, Qiquan; Revanna, Bhavya N; Madegowda, Mahendra; Dasappa, Jagadeesh P; Kamble, Ravindra R

2018-03-01

A series of novel coumarin pyrazoline moieties combined with tetrazoles, 3-(1-phenyl-4-(1H-tetrazol-5-yl)-1H-pyrazol-3-yl)-2H-chromen-2-one, 6-chloro-3-(1-phenyl-4-(1H-tetrazol-5-yl)-1H-pyrazol-3-yl)-2H-chromen-2-one, 6-bromo-3-(1-phenyl-4-(1H-tetrazol-5-yl)-1H-pyrazol-3-yl)-2H-chromen-2-one and 6-bromo-3-(1-(4-bromophenyl)-4-(1H-tetrazol-5-yl)-1H pyrazol-3-yl)-2H-chromen-2-one7(a-d), were designed and synthesized. Single crystal X-ray diffraction and their interactions were studied by Hirshfeld surface analysis. Thermal stabilities and electrochemical properties of these compounds were examined from differential scanning calorimetry (DSC), thermogravimetric (TGA) and cyclic voltammetric (CV) studies. Their spectroscopic properties were analyzed in various alcohols and general solvents by UV-Vis absorption, fluorescence and time-resolved spectroscopy. In addition, the ground and excited state electronic properties were investigated using density functional theory (DFT). The calculated highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) and energy band gap (E g ) values have revealed the effect of substitution of halogens. The substitution has equally affected the ground and excited states of 7(a-d) compounds. The solvatochromism on absorption, fluorescence spectra and fluorescence lifetimes of these compounds was investigated. All these results showed the chromen-2-one of pyrazoline tetrazole derivatives could play an important role in photonic and electronic devices. © 2017 The American Society of Photobiology.

Ultrafast forward and backward electron transfer dynamics of coumarin 337 in hydrogen-bonded anilines as studied with femtosecond UV-pump/IR-probe spectroscopy.

PubMed

Ghosh, Hirendra N; Verma, Sandeep; Nibbering, Erik T J

2011-02-10

Femtosecond infrared spectroscopy is used to study both forward and backward electron transfer (ET) dynamics between coumarin 337 (C337) and the aromatic amine solvents aniline (AN), N-methylaniline (MAN), and N,N-dimethylaniline (DMAN), where all the aniline solvents can donate an electron but only AN and MAN can form hydrogen bonds with C337. The formation of a hydrogen bond with AN and MAN is confirmed with steady state FT-IR spectroscopy, where the C═O stretching vibration is a direct marker mode for hydrogen bond formation. Transient IR absorption measurements in all solvents show an absorption band at 2166 cm(-1), which has been attributed to the C≡N stretching vibration of the C337 radical anion formed after ET. Forward electron transfer dynamics is found to be biexponential with time constants τ(ET)(1) = 500 fs, τ(ET)(2) = 7 ps in all solvents. Despite the presence of hydrogen bonds of C337 with the solvents AN and MAN, no effect has been found on the forward electron transfer step. Because of the absence of an H/D isotope effect on the forward electron transfer reaction of C337 in AN, hydrogen bonds are understood to play a minor role in mediating electron transfer. In contrast, direct π-orbital overlap between C337 and the aromatic amine solvents causes ultrafast forward electron transfer dynamics. Backward electron transfer dynamics, in contrast, is dependent on the solvent used. Standard Marcus theory explains the observed backward electron transfer rates.

Hyaluronic acid-coated liposomes for targeted delivery of paclitaxel, in-vitro characterization and in-vivo evaluation.

PubMed

Ravar, Fatemeh; Saadat, Ebrahim; Gholami, Mehdi; Dehghankelishadi, Pouya; Mahdavi, Mehdi; Azami, Samira; Dorkoosh, Farid A

2016-05-10

Breast cancer is the leading cause of cancer death in women. Chemotherapy is regarded as the most essential strategy in inhibiting the proliferation of tumor cells. Paclitaxel is a widely used taxane; however, the side effects of available Cremophor-based formulations and also the limitations of passive targeting uncovered an essential need to develop tumor-specific targeted nanocarriers. A hyaluronic acid targeted liposomal formulation of paclitaxel was prepared in which, hyaluronic acid was electrostatistically attracted to the surface of liposomes. Liposomes, had a particle size of 106.4±3.2nm, a weakly negative zeta potential of -9.7±0.8mV and an acceptable encapsulation efficiency of 92.1±1.7%. The release profile of liposomes in buffer showed that 95% of PTX was released during 40h. Confocal laser scanning microscopy and flow cytometry analysis showed the greater cellular internalization of coumarin-loaded liposomes compared to free coumarin. MTT assay on 4T1 and T47D cells demonstrated the stronger cytotoxic activity of liposomes in comparison to free paclitaxel. Cell cycle analysis showed that cells were mainly blocked at G2/M phases after 48h treatment with liposomes. In vivo real time imaging on 4T1 tumor-bearing mice revealed that the liposomal formulation mainly accumulated in the tumor area. Liposomes also had better antitumor efficacy against Cremophor-based formulation. In conclusion, hyaluronic acid targeted paclitaxel liposome can serve as a promising targeted formulation of paclitaxel for future cancer chemotherapy. Copyright © 2016 Elsevier B.V. All rights reserved.

Main constituents from the seeds of Vietnamese Cnidium monnieri and cytotoxic activity.

PubMed

Dien, Pham Huu; Nhan, Nguyen Thi; Le Thuy, Hoang Thi; Quang, Dang Ngoc

2012-01-01

From the ethyl acetate extract of the seeds of Vietnamese Cnidium monnieri L., three coumarins, osthole (1), xanthotoxin (2), imperatorin (3) and a sterol, daucosterol (4) have been purified. Their structures were elucidated by spectroscopic analysis. Furthermore, 8-(3-hidroxy-3-methylbutyl)-7-methoxycoumarin (5) was synthesised from osthole (1) with a good yield (80%). In addition, compound 1 and its synthesis product (5) show moderate and non-selective cytotoxic activities against four cancer cells, KB (a human epidermal carcinoma), MCF7 (human breast carcinoma), SK-LU-1 (human lung carcinoma) and HepG2 (hepatocellular carcinoma).

Therapeutic Potential of Medicinal Plants and Their Constituents on Lung Inflammatory Disorders

PubMed Central

Kim, Hyun Pyo; Lim, Hyun; Kwon, Yong Soo

2017-01-01

Acute bronchitis and chronic obstructive pulmonary diseases (COPD) are essentially lung inflammatory disorders. Various plant extracts and their constituents showed therapeutic effects on several animal models of lung inflammation. These include coumarins, flavonoids, phenolics, iridoids, monoterpenes, diterpenes and triterpenoids. Some of them exerted inhibitory action mainly by inhibiting the mitogen-activated protein kinase pathway and nuclear transcription factor-κB activation. Especially, many flavonoid derivatives distinctly showed effectiveness on lung inflammation. In this review, the experimental data for plant extracts and their constituents showing therapeutic effectiveness on animal models of lung inflammation are summarized. PMID:27956716

Epigenetic modifiers alter the secondary metabolite composition of a plant endophytic fungus, Pestalotiopsis crassiuscula obtained from the leaves of Fragaria chiloensis.

PubMed

Yang, Xiao-Long; Huang, Le; Ruan, Xiao-Li

2014-01-01

The addition of the DNA methyltransferase inhibitor 500 μM 5-azacytidine to the culture medium of a plant endophytic fungus, Pestalotiopsis crassiuscula, obtained from the leaves of Fragaria chiloensis, dramatically altered the profiles of its metabolites and resulted in the isolation of one new coumarin (1), along with six known compounds (2-7). HPLC profiles revealed that only compounds 3, 4, and 7 belonged to the new induced secondary metabolites. The structures of all isolated compounds were elucidated on the basis of extensive analysis of NMR spectra.

Stimulated parametric emission microscopy.

PubMed

Isobe, Keisuke; Kataoka, Shogo; Murase, Rena; Watanabe, Wataru; Higashi, Tsunehito; Kawakami, Shigeki; Matsunaga, Sachihiro; Fukui, Kiichi; Itoh, Kazuyoshi

2006-01-23

We propose a novel microscopy technique based on the four-wave mixing (FWM) process that is enhanced by two-photon electronic resonance induced by a pump pulse along with stimulated emission induced by a dump pulse. A Ti:sapphire laser and an optical parametric oscillator are used as light sources for the pump and dump pulses, respectively. We demonstrate that our proposed FWM technique can be used to obtain a one-dimensional image of ethanol-thinned Coumarin 120 solution sandwiched between a hole-slide glass and a cover slip, and a two-dimensional image of a leaf of Camellia sinensis.

Advances in the Study of the Structures and Bioactivities of Metabolites Isolated from Mangrove-Derived Fungi in the South China Sea

PubMed Central

Wang, Xin; Mao, Zhi-Gang; Song, Bing-Bing; Chen, Chun-Hua; Xiao, Wei-Wei; Hu, Bin; Wang, Ji-Wen; Jiang, Xiao-Bing; Zhu, Yong-Hong; Wang, Hai-Jun

2013-01-01

Many metabolites with novel structures and biological activities have been isolated from the mangrove fungi in the South China Sea, such as anthracenediones, xyloketals, sesquiterpenoids, chromones, lactones, coumarins and isocoumarin derivatives, xanthones, and peroxides. Some compounds have anticancer, antibacterial, antifungal and antiviral properties, but the biosynthesis of these compounds is still limited. This review summarizes the advances in the study of secondary metabolites from the mangrove-derived fungi in the South China Sea, and their biological activities reported between 2008 and mid-2013. PMID:24084782

[Chemical and biological evaluation of the effect of plant extracts against Plasmodium berghei].

PubMed

Castro, O; Barrios, M; Chinchilla, M; Guerrero, O

1996-08-01

Extracts from thirteen species of plants were evaluated by "in vivo" antimalarial test against plasmodium berghei effects. Significant activities were observed in the ethyl acetate and aqueous extracts, elaborated of Cedrela tonduzii leaves, Trichilia havanensis and Trichilia americana barks, Neurolaena lobata and Gliricidia sepium leaves and Duranta repens fruits. Compounds identified include flavanoids, coumarins, mellilotic acid and iridoids which some kind of biodynamic activity has previously been reported. The flavone quercetin 1 purified from C. tonduzii gave strong antimalarial activity, however, its respective glucosides (quercetin 3-glucoside 2 y robinine 7) showed little significant activity.

Preparation of magnetic and pH-responsive chitosan microcapsules via sonochemical method.

PubMed

Xu, Fengzhi; Zhao, Tianqi; Wang, Shurong; Liu, Songfeng; Yang, Ting; Li, Zhanfeng; Wang, Hongyan; Cui, Xuejun

2016-01-01

Magnetic and pH-responsive chitosan microcapsules (MPRCMCs) were prepared by a simple sonochemical method. Superparamagnetic oleic acid modified Fe3O4 nanoparticles (OA-Fe3O4 NPs) and hydrophobic drugs could be directly loaded into MPRCMCs during sonication. The obtained microcapsules had a well-defined spherical morphology with the average size of 2 μm. The microcapsules showed an excellent magnetic property. In addition, the pH-responsive controlled release of coumarin 6 (C6) from MPRCMCs indicated that the developed microcapsules could be a promising candidate for drugs carriers.

Imaging Lysosomal pH Alteration in Stressed Cells with a Sensitive Ratiometric Fluorescence Sensor.

PubMed

Xue, Zhongwei; Zhao, Hu; Liu, Jian; Han, Jiahuai; Han, Shoufa

2017-03-24

The organelle-specific pH is crucial for cell homeostasis. Aberrant pH of lysosomes has been manifested in myriad diseases. To probe lysosome responses to cell stress, we herein report the detection of lysosomal pH changes with a dual colored probe (CM-ROX), featuring a coumarin domain with "always-on" blue fluorescence and a rhodamine-lactam domain activatable to lysosomal acidity to give red fluorescence. With sensitive ratiometric signals upon subtle pH changes, CM-ROX enables discernment of lysosomal pH changes in cells undergoing autophagy, cell death, and viral infection.

Cytotoxic constituents of Achillea clavennae from Montenegro.

PubMed

Trifunović, Snezana; Vajs, Vlatka; Juranić, Zorica; Zizak, Zeljko; Tesević, Vele; Macura, Slobodan; Milosavljević, Slobodan

2006-05-01

Examination of the aerial parts of Achillea clavennae afforded eight guaianolides (1-8), three bisabolenes (9-11), four flavonols (12-15), sesamin (lignan) and isofraxidin (coumarin). The structures of the new compounds (2, 4, 5, 7 and 10) were determined by spectroscopic methods. The antiproliferative action of 2, 8, 9 and 12 were tested to HeLa, K562 and Fem-X human cancer cell lines. Guaianolides 2 (9alpha-acetoxyartecanin) and 8 (apressin) showed significant cytotoxic effects to all tested lines and inducumenone (9) exhibited a moderate activity. The most active was flavonol centaureidin (12), already known as cytotoxic compound.

Fluorescence method for enzyme analysis which couples aromatic amines with aromatic aldehydes

DOEpatents

Smith, R.E.; Dolbeare, F.A.

1980-10-21

Analysis of proteinases is accomplished using conventional amino acid containing aromatic amine substrates. Aromatic amines such as 4-methoxy-2-naphthylamine (4M2NA), 2-naphthylamine, aminoisophthalic acid dimethyl ester, p-nitroaniline, 4-methoxy-1-aminofluorene and coumarin derivatives resulting from enzymatic hydrolysis of the substrate couples with aromatic aldehydes such as 5-nitrosalicylaldehyde (5-NSA), benzaldehyde and p-nitrobenzaldehyde to produce Schiff-base complexes which are water insoluble. Certain Schiff-base complexes produce a shift from blue to orange-red (visible) fluorescence. Such complexes are useful in the assay of enzymes. No Drawings

Guest-Release Control in Enzyme-Sensitive, Amphiphilic-Dendrimer-Based Nanoparticles through Photochemical Crosslinking

PubMed Central

Raghupathi, Krishna R.; Azagarsamy, Malar A.; Thayumanavan, S.

2012-01-01

Stimuli sensitive, facially amphiphilic dendrimers have been synthesized and their enzyme-responsive nature has been determined with dual fluorescence responses of both covalently conjugated and non-covalently bound reporter units. These dual responses are correlated to ascertain the effect of enzymatic action on micellar aggregates and the consequential guest release. The release of the guest molecule is conveniently tuned by stabilizing the micellar aggregates through photochemical crosslinking of hydrophobic coumarin units. This photo-crosslinking is also utilized as a tool to investigate the mode of enzyme-substrate interaction in the context of aggregate-monomer equilibrium. PMID:21887830

Fluorescence method for enzyme analysis which couples aromatic amines with aromatic aldehydes

DOEpatents

Smith, Robert E. [557 Escondido Cir., Livermore, CA 94550; Dolbeare, Frank A. [5178 Diane La., Livermore, CA 94550

1980-10-21

Analysis of proteinases is accomplished using conventional amino acid containing aromatic amine substrates. Aromatic amines such as 4-methoxy-2-naphthylamine (4M2NA), 2-naphthylamine, aminoisophthalic acid dimethyl ester, p-nitroaniline, 4-methoxy-1-aminofluorene and coumarin derivatives resulting from enzymatic hydrolysis of the substrate couples with aromatic aldehydes such as 5-nitrosalicylaldehyde (5-NSA), benzaldehyde and p-nitrobenzaldehyde to produce Schiff-base complexes which are water insoluble. Certain Schiff-base complexes produce a shift from blue to orange-red (visible) fluorescence. Such complexes are useful in the assay of enzymes.

Fluorescence method for enzyme analysis which couples aromatic amines with aromatic aldehydes

DOEpatents

Smith, Robert E.; Dolbeare, Frank A.

1979-01-01

Analysis of proteinases is accomplished using conventional amino acid containing aromatic amine substrates. Aromatic amines such as 4-methoxy-2-naphthylamine (4M2NA), 2-naphthylamine, aminoisophthalic acid dimethyl ester, p-nitroaniline, 5-methoxy-1-aminofluorene and coumarin derivatives resulting from enzymatic hydrolysis of the substrate couples with aromatic aldehydes such as 5-nitrosalicylaldehyde (5-NSA), benzaldehyde and p-nitrobenzaldehyde to produce Schiff-base complexes which are water insoluble. Certain Schiff-base complexes produce a shift from blue to orange-red (visible) fluorescence. Such complexes are useful in the assay of enzymes.

In vitro inducible nitric oxide synthesis inhibitory active constituents from Fraxinus rhynchophylla.

PubMed

Kim, N Y; Pae, H O; Ko, Y S; Yoo, J C; Choi, B M; Jun, C D; Chung, H T; Inagaki, M; Higuchi, R; Kim, Y C

1999-10-01

Bioassay-guided fractionation of an H2O extract of the barks of Fraxinus rhynchophylla has furnished two inducible nitric oxide synthase (iNOS) inhibitory compounds, ferulaldehyde (1) and scopoletin (3) together with a coumarin, fraxidin (2). Compounds 1 and 3 showed inhibition of nitric oxide (NO) synthesis in a dose-dependent manner by murine macrophage-like RAW 264.7 cells stimulated with interferon-gamma (IFN-gamma) plus lipopolysaccharide (LPS). The inhibition of NO synthesis of 1 was reflected in the decreased amount of iNOS protein, as determined by Western blotting.

Osthole protects sepsis-induced acute kidney injury via down-regulating NF-κB signal pathway

PubMed Central

Qu, Hong-lin; Zhang, Yue-juan; Wang, Xue-kai; Fan, Hua-Ying

2017-01-01

BACKGROUND AND PURPOSE As a natural coumarin derivative from the Cnidium monnieri(L)Cusson fruit, osthole consists of 7-methoxy-8-isopentenoxy-coumarin. The purpose of this research is to study the mechanism and effect of osthole on sepsis-induced acute kidney injury. EXPERIMENTAL APPROACH The protective effect of osthole on mouse macrophage RAW 264.7 and HK-2 cells induced by LPS in vitro and on acute kidney injury model induced by sepsis and established by puncture and cecal ligation (CLP) in vivo were tested. KEY RESULTS Osthole (20, 40 mg·kg−1) group can greatly attenuate the changes of the score and kidney histopathology damage and enhance the survival time of septic mice. After the CLP surgery, degrees of SCr and BUN related to kidney injury were upregulated. The concentrations of SCr and BUN can be greatly reduced by treatment with osthole. Furthermore, osthole could increase bacterial killing activity and phagocytic activities of macrophages impaired after CLP partly and attenuate blood bacterial counts and leukocyte infiltration markedly. Furthermore, osthole can suppress NF-κB signal pathway through the inhibition of the nuclear translocation by regulating phosphorylation of IκBα and IKKβ and hinder the production of chemoattractant (MCP-1 and IL-8) and proinflammatory cytokines (TNF-α, IL-1β and IL-6). CONCLUSION AND IMPLICATIONS Mainly because of its immunomodulatory properties and anti-inflammatory activity, which might be closely associated with suppression of the stimulation of the NF-κB signal pathway, osthole has protective effect on sepsis-induced kidney injury. It can be seen from such evidence that osthole can be potentially applied in the treatment of acute kidney injury. PMID:27902475

Osthole protects sepsis-induced acute kidney injury via down-regulating NF-κB signal pathway.

PubMed

Yu, Chen; Li, Peng; Qi, Dong; Wang, Lei; Qu, Hong-Lin; Zhang, Yue-Juan; Wang, Xue-Kai; Fan, Hua-Ying

2017-01-17

As a natural coumarin derivative from the Cnidium monnieri(L)Cusson fruit, osthole consists of 7-methoxy-8-isopentenoxy-coumarin. The purpose of this research is to study the mechanism and effect of osthole on sepsis-induced acute kidney injury. The protective effect of osthole on mouse macrophage RAW 264.7 and HK-2 cells induced by LPS in vitro and on acute kidney injury model induced by sepsis and established by puncture and cecal ligation (CLP) in vivo were tested. Osthole (20, 40 mg·kg-1) group can greatly attenuate the changes of the score and kidney histopathology damage and enhance the survival time of septic mice. After the CLP surgery, degrees of SCr and BUN related to kidney injury were upregulated. The concentrations of SCr and BUN can be greatly reduced by treatment with osthole. Furthermore, osthole could increase bacterial killing activity and phagocytic activities of macrophages impaired after CLP partly and attenuate blood bacterial counts and leukocyte infiltration markedly. Furthermore, osthole can suppress NF-κB signal pathway through the inhibition of the nuclear translocation by regulating phosphorylation of IκBα and IKKβ and hinder the production of chemoattractant (MCP-1 and IL-8) and proinflammatory cytokines (TNF-α, IL-1β and IL-6). Mainly because of its immunomodulatory properties and anti-inflammatory activity, which might be closely associated with suppression of the stimulation of the NF-κB signal pathway, osthole has protective effect on sepsis-induced kidney injury. It can be seen from such evidence that osthole can be potentially applied in the treatment of acute kidney injury.

[Study on transport mechanism of baicalin in Scutellariae radix extracts and effect of Angelica dahurica extracts on transport of baicalin by Caco-2 cell monolayer model].

PubMed

Liang, Xin-Li; Zhu, Meng-Liang; Zhao, Li-Jun; Zhao, Guo-Wei; Liao, Zheng-Gen; Cao, Yun-Chao; Yang, Ming

2013-07-01

To study the transport mechanism of baicalin of Scutellariae Radix extracts and the effect of Angelica dahurica extracts on the intestinal absorption of baicalin by using Caco-2 cell monolayer model, in order to analyze the effect mechanism of Angelica dahurica extracts on the intestinal absorption of baicalin. The Caco-2 cell monolayer model was established with human colonic adenocarcinoma cells, and used to study the effect of pH, time, drug concentration and temperature on the transport of baicalin in Scutellariae Radix extracts, the effect of P-gp and MRP protein-dedicated inhibitors on the bidirectional transport of baicalin in Caco-2 cell model, and the effect of angelica root extracts on baicalin absorption and transport. Baicalin was absorbed well at 37 degrees C and under pH 7.4 condition and concentration dependent. Its proteins became inactive at 4 degrees C, with a low transport. The bi-drectional transfer PDR was 0. 54. After P-gp inhibitor verapamil and MRP inhibitor probenecid were added, the value of PappBL-AP of baicalin decreased, but without any difference in PDR. The transport of baicalin was improved by 2.34, 3.31 and 3.13 times, after A. dahurica extract coumarin, volatile oil, and mixture of coumarin and volatile oil. The transport mechanism of baicalin is mainly passive transfer and supplemented with efflux proteins involved. A. dahurica extracts can enhance the absorption of baicalin, which may be related to the passive transfer merchanism of baicalin. A. dahurica extracts' effect in opening the close junction among cells may be related to its expression or function in inhibiting efflux proteins.

Evaluating excited state atomic polarizabilities of chromophores† †Electronic supplementary information (ESI) available: Basis set dependence, definition of bond charges, Romberg differentiation, python script to calculate atomic polarizabilities, influence of the cavity radius, atomic polarizabilities of coumarin 153, all tables in atomic units. See DOI: 10.1039/c7cp08549d

PubMed Central

Heid, Esther

2018-01-01

Ground and excited state dipoles and polarizabilities of the chromophores N-methyl-6-oxyquinolinium betaine (MQ) and coumarin 153 (C153) in solution have been evaluated using time-dependent density functional theory (TD-DFT). A method for determining the atomic polarizabilities has been developed; the molecular dipole has been decomposed into atomic charge transfer and polarizability terms, and variation in the presence of an electric field has been used to evaluate atomic polarizabilities. On excitation, MQ undergoes very site-specific changes in polarizability while C153 shows significantly less variation. We also conclude that MQ cannot be adequately described by standard atomic polarizabilities based on atomic number and hybridization state. Changes in the molecular polarizability of MQ (on excitation) are not representative of the local site-specific changes in atomic polarizability, thus the overall molecular polarizability ratio does not provide a good approximation for local atom-specific polarizability changes on excitation. Accurate excited state force fields are needed for computer simulation of solvation dynamics. The chromophores considered in this study are often used as molecular probes. The methods and data reported here can be used for the construction of polarizable ground and excited state force fields. Atomic and molecular polarizabilities (ground and excited states) have been evaluated over a range of functionals and basis sets. Different mechanisms for including solvation effects have been examined; using a polarizable continuum model, explicit solvation and via sampling of clusters extracted from a MD simulation. A range of different solvents have also been considered. PMID:29542743

Ex Vivo and in Vivo Evaluation of the Effect of Coating a Coumarin-6-Labeled Nanostructured Lipid Carrier with Chitosan-N-acetylcysteine on Rabbit Ocular Distribution.

PubMed

Liu, Dandan; Li, Jinyu; Cheng, Bingchao; Wu, Qingyin; Pan, Hao

2017-08-07

This study is focused on further understanding the characteristics of chitosan-N-acetylcysteine surface-modified nanostructured lipid carriers (CS-NAC-NLCs) in their interaction with ocular mucosa. Coumarin-6 (C6)-labeled NLCs, including uncoated NLCs, chitosan hydrochloride (CH)-, and CS-NAC-coated NLCs, were developed using a melt-emulsification technique and subsequently decorated with different types or portions of chitosan derivatives. Mucoadhesion was evaluated ex vivo using a flow-through process with fluorescence detection. The results demonstrated that the presence of CS-NAC on the C6-NLC surface provided the most obvious enhancement in adhesion due to the formation of both noncovalent (ionic) and covalent (disulfide bridges) interactions with mucus chains. Meanwhile, the concentration of CS-NAC in the formulation positively influenced the viscosity of the nanoparticles and hence prolonged their retention in the ocular tissue. Transcorneal penetration studies revealed that CS-NAC-NLC particles were able to penetrate through the entire corneal epithelium primarily via a transcellular route. The transport depth and velocity strongly relied on the modification material and the particle size. Ex vivo fluorescence imaging and in vivo ocular distribution investigations showed that C6 was broadly distributed in rabbit eye tissues and absorbed by aqueous humor after CS-NAC-NLC instillation. In relation to C6 eye drops, CS-NAC-NLCs achieved considerably higher C max (4.01-fold), MRT 0-∞ (1.87-fold), and AUC 0-∞ (16.29-fold) in the aqueous humor. Moreover, the increase in drug absorption was greater in the cornea than in the conjunctiva. Thereby, it is possible to draw a conclusion that CS-NAC-NLCs presented great potential for drug application to the front portion of the eye.

Discovery of a novel calcium-sensitive fluorescent probe for α-ketoglutarate.

PubMed

Gan, Lin-Lin; Chen, Lin-Hai; Nan, Fa-Jun

2017-12-01

α-Ketoglutarate (α-KG), a pivotal metabolite in energy metabolism, has been implicated in nonalcoholic fatty liver disease (NAFLD) and several cancers. It is recently proposed that plasma α-KG is a surrogate biomarker of NAFLD. Here, we report the development of a novel "turn-on" chemosensor for α-KG that contains a coumarin moiety as a fluorophore. Using benzothiazole-coumarin (BTC) as inspiration, we designed a probe for calcium ion recognition that possesses a unique fluorophore compared with previously reported probes for α-KG measurement. This chemosensor is based on the specific Schiff base reaction and the calcium ion recognition property of the widely used calcium indicator BTC. The probe was synthesized, and a series of parallel experiments were conducted to optimize the chemical recognition process. Compared to the initial weak fluorescence, a remarkable 7.6-fold enhancement in fluorescence intensity (I/I 0 at 495 nm) was observed for the conditions in which the probe (1 μmol/L), α-KG (50 μmol/L), and Ca 2+ (100 μmol/L) were incubated at 30 °C in EtOH. The probe displayed good selectivity for α-KG even in an environment with an abundance of amino acids and other interfering species such as glutaric acid. We determined that the quantitative detection range of α-KG in EtOH was between 5 and 50 μmol/L. Finally, probe in serum loaded with α-KG (10 mmol/L) showed a 7.4-fold fluorescence enhancement. In summary, a novel probe for detecting the biomarker α-KG through a typical Schiff base reaction has been discovered. With further optimization, this probe may be a good alternative for detecting the physiological metabolite α-KG.

Theoretical Studies on Two-Photon Fluorescent Hg2+ Probes Based on the Coumarin-Rhodamine System.

PubMed

Zhang, Yujin; Leng, Jiancai

2017-07-20

The development of fluorescent sensors for Hg 2+ has attracted much attention due to the well-known adverse effects of mercury on biological health. In the present work, the optical properties of two newly-synthesized Hg 2+ chemosensors based on the coumarin-rhodamine system (named Pro1 and Pro2) were systematically investigated using time-dependent density functional theory. It is shown that Pro1 and Pro2 are effective ratiometric fluorescent Hg 2+ probes, which recognize Hg 2+ by Förster resonance energy transfer and through bond energy transfer mechanisms, respectively. To further understand the mechanisms of the two probes, we have developed an approach to predict the energy transfer rate between the donor and acceptor. Using this approach, it can be inferred that Pro1 has a six times higher energy transfer rate than Pro2. Thus the influence of spacer group between the donor and acceptor on the sensing performance of the probe is demonstrated. Specifically, two-photon absorption properties of these two probes are calculated. We have found that both probes show significant two-photon responses in the near-infrared light region. However, only the maximum two-photon absorption cross section of Pro1 is greatly enhanced with the presence of Hg 2+ , indicating that Pro1 can act as a potential two-photon excited fluorescent probe for Hg 2+ . The theoretical investigations would be helpful to build a relationship between the structure and the optical properties of the probes, providing information on the design of efficient two-photon fluorescent sensors that can be used for biological imaging of Hg 2+ in vivo.

Rotational dynamics of coumarin-153 and 4-aminophthalimide in 1-ethyl-3-methylimidazolium alkylsulfate ionic liquids: effect of alkyl chain length on the rotational dynamics.

PubMed

Das, Sudhir Kumar; Sarkar, Moloy

2012-01-12

Rotational dynamics of two neutral organic solutes, coumarin-153 (C-153) and 4-aminophthalimide (AP), with only the latter having hydrogen-bond-donating ability, has been investigated in a series of 1-ethyl-3-methylimidazolium alkyl sulfate ionic liquids as a function of temperature. The ionic liquids differ only in the length of the linear alkyl side chain (alkyl = ethyl, butyl, hexyl, and octyl) on the anionic moiety. The present study has been undertaken to examine the role of alkyl side chains on the rotational dynamics of the two solutes in these ionic liquids. Analysis of the results using Stokes-Einstein-Debye hydrodynamic theory indicates that the rotational dynamics of C-153 lies between the stick and slip boundary condition in the ethyl analogue and finally reaches subslip condition as in case of the octyl substituent. The observed rotational behavior of C-153 has been explained on the basis of an increase in the size of the solvent, which offers lower friction for solute rotation. On the other hand, AP shows superstick behavior in the ethyl system and exceeds the stick limit in the octyl derivative. Superstick behavior of AP has been attributed to the specific hydrogen-bonding interaction between AP and the sulfate moiety. Proton NMR investigation confirms the hydrogen-bonding interaction between the N-H hydrogen of AP and the ionic liquid. The decrease in rotational coupling constant values for AP with increasing length of alkyl side chains has been attributed to the decrease in the solute-solvent-specific interaction with an increase in the alkyl side chain length on the sulfate moiety.

[Effects of sub-micro emulsion composition on cellular disposition of incorporated lipophilic drug].

PubMed

Sun, Xiao-Yi; Xiang, Zhi-Qiang; Wu, Shuo; Lv, Yuan-Yuan; Liang, Wen-Quan

2013-09-01

To investigate the effects of sub-micro emulsion composition on cellular uptake and disposition of incorporated lipophilic drug. Sub-micro emulsions containing 10 % oil, 1.2 % lecithin and 2.25 % glycerol were prepared, and the fluorescent agent coumarin 6 was used as a model drug. The effects of oil types, co-surfactants and cationic lipid on uptake and elimination kinetics of 6-coumarin in HeLa cells were studied. The uptake mechanism of sub-micro emulsions was further investigated. Oil type and Tweens had no influence on the cellular uptake. Modifications of surfactants with Span series increased the cellular influx, among which Span 20 with hydrophilic-lipophilic balance (HLB) value of 8.6 was the best enhancer. The intracellular drug level reached up to (46.09 ± 1.98)ng/μg protein which had significant difference with control group [(38.54 ± 0.34)ng/μg protein]. The positively charged emulsions significantly increased the uptake rate constant and elimination rate constant which were 4 times and 1.5 times of those in anionic groups, respectively. The uptake enhancement was also observed in cationic emulsions, cellular concentrations at plateau were (42.73 ± 0.84)ng/μg protein, which was about 3 times of that in anionic emulsions [(15.71 ± 0.74)ng/μg protein], when extracellular drug concentration kept at 100 ng/ml. Cationic emulsions delivered the payload mainly by direct drug transfer to contacted cells, while the negative ones depended on both drug passive diffusion and clathrin-mediated endocytosis of drug containing oil droplets which accounted for 20% of the intracellular drug. Interfacial characteristic of sub-micro emulsions such as co-surfactants HLB as well as zeta potentials can influence lipophilic drug both in cellular uptake and elimination.

Simultaneous determination of chromones and coumarins in Radix Saposhnikoviae by high performance liquid chromatography with diode array and tandem mass detectors.

PubMed

Kim, Min Kyung; Yang, Dong-Hyug; Jung, Mihye; Jung, Eun Ha; Eom, Han Young; Suh, Joon Hyuk; Min, Jung Won; Kim, Unyong; Min, Hyeyoung; Kim, Jinwoong; Han, Sang Beom

2011-09-16

Methods using high performance liquid chromatography with diode array detection (HPLC-DAD) and tandem mass spectrometry (HPLC-MS/MS) were developed and validated for the simultaneous determination of 5 chromones and 6 coumarins: prim-O-glucosylcimifugin (1), cimifugin (2), nodakenin (3), 4'-O-β-d-glucosyl-5-O-methylvisamminol (4), sec-O-glucosylhamaudol (5), psoralen (6), bergapten (7), imperatorin (8), phellopterin (9), 3'-O-angeloylhamaudol (10) and anomalin (11), in Radix Saposhnikoviae. The separation conditions for HPLC-DAD were optimized using an Ascentis Express C18 (4.6 mm×100 mm, 2.7 μm particle size) fused-core column. The mobile phase was composed of 10% aqueous acetonitrile (A) and 90% acetonitrile (B) and the elution was performed under a gradient mode at a flow rate of 1.0 mL/min. The detection wavelength was set at 300 nm. The HPLC-DAD method yielded a base line separation of the 11 components in 50% methanol extract of Radix Saposhnikoviae with no interfering peaks detected. The HPLC-DAD method was validated in terms of linearity, accuracy and precision (intra- and inter-day), limit of quantification (LOQ), recovery, and robustness. Specific determination of the 11 components was also accomplished by a triple quadrupole tandem mass spectrometer equipped with an electrospray ionization (ESI) source. This HPLC-MS/MS method was also validated by determining the linearity, limit of quantification, accuracy, and precision. Quantification of the 11 components in 51 commercial Radix Saposhnikoviae samples was successfully performed using the developed HPLC-DAD method. The identity, batch-to-batch consistency, and authenticity of Radix Saposhnikoviae were successfully monitored by the proposed HPLC-DAD and HPLC-MS/MS methods. Copyright © 2011 Elsevier B.V. All rights reserved.

Auraptene, a citrus coumarin, inhibits 12-O-tetradecanoylphorbol-13-acetate-induced tumor promotion in ICR mouse skin, possibly through suppression of superoxide generation in leukocytes.

PubMed

Murakami, A; Kuki, W; Takahashi, Y; Yonei, H; Nakamura, Y; Ohto, Y; Ohigashi, H; Koshimizu, K

1997-05-01

Coumarin-related compounds, auraptene and umbelliferone, have been isolated from the cold-pressed oil of natsumikan (Citrus natsudaidai HAYATA), and tested as inhibitors of tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced Epstein-Barr virus activation in Raji cells. The 50% inhibitory concentration (IC50) of auraptene (18 microM) was almost equal to that of genistein. Umbelliferone, which lacks a geranyloxyl group present in auraptene, was less active (IC50 = 450 microM). In a two-stage carcinogenesis experiment with 7,12-dimethylbenz[a] anthracene (topical application at 0.19 mumol) and TPA (topical application at 1.6 nmol) in ICR mouse skin, topical application of auraptene (at 160 nmol) significantly reduced tumor incidence and the numbers of tumors per mouse by 27% (P < 0.01) and 23% (P < 0.05), respectively. Auraptene at a concentration of 50 microM markedly suppressed superoxide (O2-) generation induced by 100 microM TPA in differentiated human promyelocytic HL-60 cells. Having no O2(-)-scavenging potential, auraptene may inhibit the multicomponent NADPH oxidase system. Inhibition of intracellular hydroperoxide formation in differentiated HL-60 cells by auraptene was also confirmed by flow-cytometric analysis using 2',7'-dichlorofluorescein diacetate as a fluorescence probe. Quantitative analyses using high-performance liquid chromatography showed the occurrence of auraptene not only in both the peels and sarcocarps of natsumikan, but also in those of hassaku orange (C. hassaku) and grapefruit (C. paradisi), and even in their bottled fresh juice form. These results indicate that auraptene is a chemopreventer of skin tumorigenesis, and implies that suppression of leukocyte activation might be the mechanism through which it inhibits tumor promotion.

Tailored on demand anti-coagulant dosing: an in vitro and in vivo evaluation of 3D printed purpose-designed oral dosage forms.

PubMed

Arafat, Basel; Qinna, Nidal; Cieszynska, Milena; Forbes, Robert T; Alhnan, Mohamed A

2018-04-16

Coumarin therapy has been associated with high levels of inter- and intra-individual variation in the required dose to reach a therapeutic anticoagulation outcome. Therefore, a dynamic system that is able to achieve accurate delivery of a warfarin dose is of significant importance. Here we assess, the ability of 3D printing to fabricate and deliver tailored individualised precision dosing using an in-vitro model. Sodium warfarin loaded filaments were compounded using hot melt extrusion (HME) and further fabricated via fused deposition modelling (FDM) 3D printing to produce capsular-ovoid-shaped dosage forms loaded at 200 and 400 µg dose. The solid dosage forms and comparator warfarin aqueous solutions were administered by oral gavage to Sprague-Dawley rats. In vitro, warfarin release was faster at pH 1.2 in comparison to pH 2. A novel UV imaging approach indicated that the erosion of the methacrylate matrix was at a rate of 16.4 and 15.2 µm/min for horizontal and vertical planes respectively. In vivo, 3D printed forms were as proportionately effective as their comparative solution form in doubling plasma exposure following a doubling of warfarin dose (184% versus 192% respectively). The 3D printed ovoids showed a lower C max of warfarin (1.51 and 3.33 mg/mL versus 2.5 and 6.44 mg/mL) and a longer T max (6 and 3.7 versus 4 and 1.5 h) in comparison to liquid formulation. This work demonstrates for the first time in vivo, the potential of FDM 3D printing to produce a tailored specific dosage form and to accurately titrate coumarin dose response to an individual patient. Copyright © 2018. Published by Elsevier B.V.

Resonance Energy Transfer Studies from Derivatives of Thiophene Substituted 1,3,4-Oxadiazoles to Coumarin-334 Dye in Liquid and Dye-Doped Polymer Media

NASA Astrophysics Data System (ADS)

Naik, Lohit; Deshapande, Narahari; Khazi, Imtiyaz Ahamed M.; Malimath, G. H.

2018-02-01

In the present work, we have carried out energy transfer studies using newly synthesised derivatives of thiophene substituted 1,3,4-oxadiazoles namely, 2-(-4-(thiophene-3-yl)phenyl)-5-(5-(thiophene-3-yl)thiophene-2-yl)-1,3,4-oxadiazole [TTO], 2-(-4-(benzo[b]thiophene-2-yl)phenyl)-5-(5-(benzo[b]thiophene-2-yl)-1,3,4-oxadiozole [TBO] and 2-(4-(4-(trifluoromethyl)phenyl)phenyl)-5-(5-(4-(trifluoromethyl)phenyl)thiophen-2-yl)-1,3,4-oxadiazole [TMO] as donors and laser dye coumarin-334 as acceptor in ethanol and dye-doped polymer (poly(methyl methacrylate) (PMMA)) media following steady-state and time-resolved fluorescence methods. Bimolecular quenching constant ( k q), translation diffusion rate parameter ( k d), diffusion length ( D l), critical transfer distance ( R 0), donor- acceptor distance ( r) and energy transfer efficiency ( E T) are calculated. It is observed that, critical transfer distance is more than the diffusion length for all the pairs. Further, bimolecular quenching constant is also more than the translation diffusion rate parameter. Hence, our experimental findings suggest that overall energy transfer is due to Förster resonance energy transfer (FRET) between donor and acceptor in both the media and for all the pairs. In addition, considerable increase in fluorescence intensity and energy transfer efficiency is observed in dye-doped polymer matrix systems as compared to liquid media. This suggests that, these donor-acceptor pairs doped in PMMA matrix may be used for applications such as energy transfer dye lasers (ETDL) to improve the efficiency and photostability, to enhance tunability and for plastic scintillation detectors.