Science.gov

Sample records for 2-thiophenecarboxylic acid derivatives

  1. Single-electron transport through a Mn12 (2-thiophenecarboxylate) single-molecule magnet

    NASA Astrophysics Data System (ADS)

    Ramsey, Christopher M.; Del Barco, Enrique; Mucciolo, Eduardo; Haque, Firoze; Khondaker, Saiful; Leuenberger, Michael; Mishra, Abhudaya; Christou, George

    2006-03-01

    We report single-electron transport measurements on Mn12 based single-molecule magnet, which has been functionalized with 2-thiophenecarboxylate ligands that bind to gold. The self-assembly of these molecules was confirmed by scanning probe microscopy and XPS measurements. Because it is well known that the molecule's environment within the crystal can have a profound influence on the quantum properties of the system, it is important to study the quantum spin dynamics in individual isolated molecules. Single electron transistor devices have been prepared for this purpose by electron beam lithography and electromigration. The transport properties of a single, isolated Mn12(2-thiophenecarboxylate) molecule were measured down to mK temperatures in a 3-D superconducting vector magnet with arbitrary field direction. The data are characteristic of a molecular single-electron transistor device where the SMM bridges the gap between two gold nanoelectrodes. Magnetic field and temperature dependence as well as theoretical aspects will be discussed.

  2. Bicyclic glutamic acid derivatives.

    PubMed

    Meyer, Udo; Bisel, Philippe; Weckert, Edgar; Frahm, August Wilhelm

    2006-05-15

    For the second-generation asymmetric synthesis of the trans-tris(homoglutamic) acids via Strecker reaction of chiral ketimines, the cyanide addition as the key stereodifferentiating step produces mixtures of diastereomeric alpha-amino nitrile esters the composition of which is independent of the reaction temperature and the type of the solvent, respectively. The subsequent hydrolysis is exclusively achieved with concentrated H(2)SO(4) yielding diastereomeric mixtures of three secondary alpha-amino alpha-carbamoyl-gamma-esters and two diastereomeric cis-fused angular alpha-carbamoyl gamma-lactams as bicyclic glutamic acid derivatives, gained from in situ stereomer differentiating cyclisation of the secondary cis-alpha-amino alpha-carbamoyl-gamma-esters. Separation was achieved by CC. The pure secondary trans-alpha-amino alpha-carbamoyl-gamma-esters cyclise on heating and treatment with concentrated H(2)SO(4), respectively, to diastereomeric cis-fused angular secondary alpha-amino imides. Their hydrogenolysis led to the enantiomeric cis-fused angular primary alpha-amino imides. The configuration of all compounds was completely established by NMR methods, CD-spectra, and by X-ray analyses of the (alphaR,1R,5R)-1-carbamoyl-2-(1-phenylethyl)-2-azabicyclo[3.3.0]octan-3-one and of the trans-alphaS,1S,2R-2-ethoxycarbonylmethyl-1-(1-phenylethylamino)cyclopentanecarboxamide. PMID:16596563

  3. Reaction of arenesulfinimidic acid derivatives with thiophenols

    SciTech Connect

    Pel'kis, N.P.; Levchenko, E.S.

    1986-07-20

    The amides and esters of N-substituted arenesulfinimidic acids are reduced by the action of thiophenols primarily to N-substituted arenesulfenamides, while the thiophenols are oxidized to the corresponding derivatives of the arenesulfinic acids.

  4. Anticancer agents derived from natural cinnamic acids.

    PubMed

    Su, Ping; Shi, Yaling; Wang, Jinfeng; Shen, Xiuxiu; Zhang, Jie

    2015-01-01

    Cancer is the most dangerous disease that causes deaths all over the world. Natural products have afforded a rich source of drugs in a number of therapeutic fields including anticancer agents. Many significant drugs have been derived from natural sources by structural optimization of natural products. Cinnamic acid has gained great interest due to its antiproliferative, antioxidant, antiangiogenic and antitumorigenic potency. Currently it has been observed that cinnamic acid and its analogs such as caffeic acid, sinapic acid, ferulic acid, and isoferulic acid display various pharmacological activities, such as immunomodulation, anti-inflammation, anticancer and antioxidant. They have served to be the major sources of potential leading anticancer compounds. In this review, we focus on the anticancer potency of cinnamic acid derivatives and novel strategies to design these derivatives. We hope this review will be useful for researchers who are interested in developing anticancer agents.

  5. Cholic acid derivatives: novel antimicrobials.

    PubMed

    Savage, P B; Li, C

    2000-02-01

    Mimics of squalamine and polymyxin B (PMB) have been prepared from cholic acid in hope of finding new antimicrobial agents. The squalamine mimics include the polyamine and sulphate functionalities found in the parent antibiotic, however, the positions relative to the steroid nucleus have been exchanged. The PMB mimics include the conservation of functionality among the polymyxin family of antibiotics, the primary amine groups and a hydrophobic chain. Although the squalamine and PMB mimics are morphologically dissimilar, they display similar activities. Both are simple to prepare and demonstrate broad spectrum antimicrobial activity against Gram-negative and Gram-positive organisms. Specific examples may be inactive alone, yet effectively permeabilise the outer membranes of Gram-negative bacteria rendering them sensitive to hydrophobic antibiotics. Problems associated with some of the squalamine and PMB mimics stem from their haemolytic activity and interactions with serum proteins, however, examples exist without these side effects which can sensitise Gram-negative bacteria to hydrophobic antibiotics. PMID:11060676

  6. Metabolism of hop-derived bitter acids.

    PubMed

    Cattoor, Ko; Dresel, Michael; De Bock, Lies; Boussery, Koen; Van Bocxlaer, Jan; Remon, Jean-Paul; De Keukeleire, Denis; Deforce, Dieter; Hofmann, Thomas; Heyerick, Arne

    2013-08-21

    In this study, in vitro metabolism of hop-derived bitter acids was investigated. Besides their well-known use as bitter compounds in beer, in several studies, bioactive properties have been related to these types of molecules. However, scientific data on the absorption, distribution, metabolism, and excretion aspects of these compounds are limited. More specific, in this study, α-acids, β-acids, and iso-α-acids were incubated with rabbit microsomes, and fractions were subjected to LC-MS/MS analysis for identification of oxidative biotransformation products. Metabolism of β-acids was mainly characterized by conversion into hulupones and the formation of a series of tricyclic oxygenated products. The most important metabolites of α-acids were identified as humulinones and hulupones. Iso-α-acids were found to be primarly metabolized into cis- and trans-humulinic acids, next to oxidized alloiso-α-acids. Interestingly, the phase I metabolites were highly similar to the oxidative degradation products in beer. These findings show a first insight into the metabolites of hop-derived bitter acids and could have important practical implications in the bioavailability aspects of these compounds, following ingestion of hop-based food products and nutraceuticals.

  7. Enzymatic synthesis of cinnamic acid derivatives.

    PubMed

    Lee, Gia-Sheu; Widjaja, Arief; Ju, Yi-Hsu

    2006-04-01

    Using Novozym 435 as catalyst, the syntheses of ethyl ferulate (EF) from ferulic acid (4-hydroxy 3-methoxy cinnamic acid) and ethanol, and octyl methoxycinnamate (OMC) from p-methoxycinnamic acid and 2-ethyl hexanol were successfully carried out in this study. A conversion of 87% was obtained within 2 days at 75 degrees C for the synthesis of EF. For the synthesis of OMC at 80 degrees C, 90% conversion can be obtained within 1 day. The use of solvent and high reaction temperature resulted in better conversion for the synthesis of cinnamic acid derivatives. Some cinnamic acid esters could also be obtained with higher conversion and shorter reaction times in comparison to other methods reported in the literature. The enzyme can be reused several times before significant activity loss was observed.

  8. Caffeic acid derivatives from Bupleurum chinense

    PubMed Central

    Haghi, G.; Hatami, A.; Mehran, M.; Hosseini, H.

    2014-01-01

    In this study, caffeic acid (CA) and its three derivatives including 3-caffeoylquinic acid (3-CQA, neochlorogenic acid), 4-caffeoylquinic acid (4-CQA, cryptochlorogenic acid), and 5-caffeoylquinic acid (5-CQA, chlorogenic acid) were identified in Bupleurum chinense aerial parts using reverse-phase high-performance liquid chromatography (RP-HPLC) with photodiode array (PDA) detector, reference compounds and chemical reactions. Separation was performed on a C18 column using gradient elution with 4% (v/v) aqueous acetic acid and acetonitrile as mobile phase at ambient temperature. In addition, the flavonoid aglycones were characterized and quantified after acid hydrolysis of the plant material. The flavonols profile showed quercetin (0.36 g per 100 g), kaempferol (1.11 g per 100 g) and isorhamnetin (0.16 g per 100 g). Total phenolic and total flavonoid contents ranged from 7.3 to 18.7% and 0.58 to 2.72% in dry plant material, respectively. PMID:25657804

  9. Novel cajaninstilbene acid derivatives as antibacterial agents.

    PubMed

    Geng, Zhi-Zhong; Zhang, Jian-Jun; Lin, Jing; Huang, Mei-Yan; An, Lin-Kun; Zhang, Hong-Bin; Sun, Ping-Hua; Ye, Wen-Cai; Chen, Wei-Min

    2015-07-15

    Discovery of novel antibacterial agents with new structural scaffolds that combat drug-resistant pathogens is an urgent task. Cajaninstilbene acid, which is isolated from pigeonpea leaves, has shown antibacterial activity. In this study, a series of cajaninstilbene acid derivatives were designed and synthesized. The antibacterial activities of these compounds against gram-negative and gram-positive bacteria, as well as nine strains of methicillin-resistant staphylococcus aureus (MRSA) bacteria are evaluated,and the related structure-activity relationships are discussed. Assays suggest that some of the synthetic cajaninstilbene acid derivatives exhibit potent antibacterial activity against gram-positive bacterial strains and MRSA. Among these compounds, 5b, 5c, 5j and 5k show better antibacterial activity than the positive control compounds. The results of MTT assays illustrate the low cytotoxicity of the active compounds.

  10. Amino acids derived from Titan Tholins

    NASA Astrophysics Data System (ADS)

    Khare, Bishun N.; Sagan, Carl; Ogino, Hiroshi; Nagy, Bartholomew; Er, Cevat; Schram, Karl H.; Arakawa, Edward T.

    1986-10-01

    An organic heteropolymer(Titan tholin) was produced by continuous dc discharge through a 0.9 N 2/0.1 CH 4 gas mixture at 0.2 mbar pressure, roughly simulating the cloudtop atmosphere of Titan. Treatment of this tholin with 6 N HCI yielded 16 amino acids by gas chromatography after derivazation to N-trifluroacetyl isopropyl esters on two different capillary columns. Identifications were confirmed by GC/MS. Glycine, aspartic acid, and α- and β-alanine were produced in greatest abundance; the total yield of amino acids was ˜ 10 -2, approximately equal to the yield of urea. The presence of "nonbiological" amino acids, the absence of serine, and the fact that the amino acids are racemic within experimental error together indicate that these molecules are not due to microbial or other contamination, but are derived from the tholin. In addition to the HCN, HC 2CN, and (CN) 2 found by Voyager, nitriles and aminonitriles should be sought in the Titanian atmosphere and, eventually, amino acids on the surface. These results suggest that episodes of liquid water in the past or future of Titan might lead to major further steps in prebiological organic chemistry on that body.

  11. Amino acids derived from Titan tholins

    NASA Technical Reports Server (NTRS)

    Khare, B. N.; Sagan, C.; Ogino, H.; Nagy, B.; Er, C.; Schram, K. H.; Arakawa, E. T.

    1986-01-01

    An organic heteropolymer (Titan tholin) was produced by continuous dc discharge through a 0.9 N2/0.1 CH4 gas mixture at 0.2 mbar pressure, roughly simulating the cloudtop atmosphere of Titan. Treatment of this tholin with 6N HCl yielded 16 amino acids by gas chromatography after derivatization of N-trifluroacetyl isopropyl esters on two different capillary columns. Identifications were confirmed by GC/MS. Glycine, aspartic acid, and alpha- and beta-alanine were produced in greatest abundance; the total yield of amino acids was approximately 10(-2), approximately equal to the yield of urea. The presence of "nonbiological" amino acids, the absence of serine, and the fact that the amino acids are racemic within experimental error together indicate that these molecules are not due to microbial or other contamination, but are derived from the tholin. In addition to the HCN, HC2CN, and (CN)2 found by Voyager, nitriles and aminonitriles should be sought in the Titanian atmosphere and, eventually, amino acids on the surface. These results suggest that episodes of liquid water in the past or future of Titan might lead to major further steps in prebiological organic chemistry on that body.

  12. 21 CFR 172.862 - Oleic acid derived from tall oil fatty acids.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Oleic acid derived from tall oil fatty acids. 172... FOOD FOR HUMAN CONSUMPTION Multipurpose Additives § 172.862 Oleic acid derived from tall oil fatty acids. The food additive oleic acid derived from tall oil fatty acids may be safely used in food and...

  13. 21 CFR 172.862 - Oleic acid derived from tall oil fatty acids.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Oleic acid derived from tall oil fatty acids. 172... FOOD FOR HUMAN CONSUMPTION Multipurpose Additives § 172.862 Oleic acid derived from tall oil fatty acids. The food additive oleic acid derived from tall oil fatty acids may be safely used in food and...

  14. 21 CFR 172.862 - Oleic acid derived from tall oil fatty acids.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Oleic acid derived from tall oil fatty acids. 172... FOOD FOR HUMAN CONSUMPTION Multipurpose Additives § 172.862 Oleic acid derived from tall oil fatty acids. The food additive oleic acid derived from tall oil fatty acids may be safely used in food and...

  15. 21 CFR 172.862 - Oleic acid derived from tall oil fatty acids.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Oleic acid derived from tall oil fatty acids. 172... FOOD FOR HUMAN CONSUMPTION Multipurpose Additives § 172.862 Oleic acid derived from tall oil fatty acids. The food additive oleic acid derived from tall oil fatty acids may be safely used in food and...

  16. 40 CFR 721.6097 - Phosphoric acid derivative (generic name).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Phosphoric acid derivative (generic... Specific Chemical Substances § 721.6097 Phosphoric acid derivative (generic name). (a) Chemical substance... phosphoric acid derivative (PMN P-95-284) is subject to reporting under this section for the significant...

  17. 40 CFR 721.6097 - Phosphoric acid derivative (generic name).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Phosphoric acid derivative (generic... Specific Chemical Substances § 721.6097 Phosphoric acid derivative (generic name). (a) Chemical substance... phosphoric acid derivative (PMN P-95-284) is subject to reporting under this section for the significant...

  18. 40 CFR 721.6097 - Phosphoric acid derivative (generic name).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Phosphoric acid derivative (generic... Specific Chemical Substances § 721.6097 Phosphoric acid derivative (generic name). (a) Chemical substance... phosphoric acid derivative (PMN P-95-284) is subject to reporting under this section for the significant...

  19. 40 CFR 721.6097 - Phosphoric acid derivative (generic name).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Phosphoric acid derivative (generic... Specific Chemical Substances § 721.6097 Phosphoric acid derivative (generic name). (a) Chemical substance... phosphoric acid derivative (PMN P-95-284) is subject to reporting under this section for the significant...

  20. 40 CFR 721.6097 - Phosphoric acid derivative (generic name).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Phosphoric acid derivative (generic... Specific Chemical Substances § 721.6097 Phosphoric acid derivative (generic name). (a) Chemical substance... phosphoric acid derivative (PMN P-95-284) is subject to reporting under this section for the significant...

  1. Titration of phosphonic acid derivatives in mixtures.

    PubMed

    Wittmann, Z

    1980-01-01

    An analytical procedure is described for the determination of the weak acids phosphonomethyliminodiacetic acid and phosphonomethyliminoacetic acid in their mixtures, and the dissociation constants of phosphonomethyliminoacetic acid are reported.

  2. Antioxidant and antimicrobial activities of cinnamic acid derivatives.

    PubMed

    Sova, M

    2012-07-01

    Cinnamic acid is an organic acid occurring naturally in plants that has low toxicity and a broad spectrum of biological activities. In the search for novel pharmacologically active compounds, cinnamic acid derivatives are important and promising compounds with high potential for development into drugs. Many cinnamic acid derivatives, especially those with the phenolic hydroxyl group, are well-known antioxidants and are supposed to have several health benefits due to their strong free radical scavenging properties. It is also well known that cinnamic acid has antimicrobial activity. Cinnamic acid derivatives, both isolated from plant material and synthesized, have been reported to have antibacterial, antiviral and antifungal properties. Acids, esters, amides, hydrazides and related derivatives of cinnamic acid with such activities are here reviewed.

  3. Degradation of benzoic acid and its derivatives in subcritical water.

    PubMed

    Lindquist, Edward; Yang, Yu

    2011-04-15

    In this research, the stability of benzoic acid and three of its derivatives (anthranilic acid, salicylic acid, and syringic acid) under subcritical water conditions was investigated. The stability studies were carried out at temperatures ranging from 50 to 350°C with heating times of 10-630 min. The degradation of the benzoic acid derivatives increased with rising temperature and the acids became less stable with longer heating time. The three benzoic acid derivatives showed very mild degradation at 150°C. Severe degradation of benzoic acid derivatives was observed at 200°C while their complete degradation occurred at 250°C. However, benzoic acid remained stable at temperatures up to 300°C. The degradation products of benzoic acid and the three derivatives were identified and quantified by HPLC and confirmed by GC/MS. Anthranilic acid, salicylic acid, syringic acid, and benzoic acid in high-temperature water underwent decarboxylation to form aniline, phenol, syringol, and benzene, respectively.

  4. Synthesis of Hydroxymethylenebisphosphonic Acid Derivatives in Different Solvents.

    PubMed

    Nagy, Dávid Illés; Grün, Alajos; Garadnay, Sándor; Greiner, István; Keglevich, György

    2016-01-01

    The syntheses of hydroxymethylenebisphosphonic acid derivatives (dronic acid derivatives) starting from the corresponding substituted acetic acids and P-reagents, mainly phosphorus trichloride and phosphorous acid are surveyed according to the solvents applied. The nature of the solvent is a critical point due to the heterogeneity of the reaction mixtures. This review sheds light on the optimum choice and ratio of the P-reactants, and on the optimum conditions. PMID:27529200

  5. Terahertz time-domain spectroscopy of four hydroxycinnamic acid derivatives.

    PubMed

    Ge, Min; Zhao, Hongwei; Wang, Wenfeng; Zhang, Zengyan; Yu, Xiaohan; Li, Wenxin

    2006-11-01

    The well-resolved absorption spectra of the hydroxycinnamic acid (HCA) derivatives, caffeic acid, ferulic acid, sinapic acid and chlorogenic acid, were measured over the frequency region from 0.3 to 2.0 THz at 294 K with terahertz time-domain spectroscopy (THz-TDS). Theoretical calculation was applied to assist the analysis and assignment of the individual THz absorption spectra of the HCA derivatives with density functional theory (DFT). The distinctive spectral features were originated from the collective motion of molecules held together by hydrogen bonds. The real and imaginary parts of dielectric function of the four HCA derivatives were also obtained. PMID:19669446

  6. Terahertz Time-Domain Spectroscopy of Four Hydroxycinnamic Acid Derivatives

    PubMed Central

    Ge, Min; Zhao, Hongwei; Zhang, Zengyan; Yu, Xiaohan; Li, Wenxin

    2006-01-01

    The well-resolved absorption spectra of the hydroxycinnamic acid (HCA) derivatives, caffeic acid, ferulic acid, sinapic acid and chlorogenic acid, were measured over the frequency region from 0.3 to 2.0 THz at 294 K with terahertz time-domain spectroscopy (THz-TDS). Theoretical calculation was applied to assist the analysis and assignment of the individual THz absorption spectra of the HCA derivatives with density functional theory (DFT). The distinctive spectral features were originated from the collective motion of molecules held together by hydrogen bonds. The real and imaginary parts of dielectric function of the four HCA derivatives were also obtained. PMID:19669446

  7. 40 CFR 721.10039 - Diethoxybenzenamine derivative, diazotized, coupled with aminonaphthalenesulfonic acid derivative...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ..., diazotized, coupled with aminonaphthalenesulfonic acid derivative, ammonium salt (generic). 721.10039 Section... derivative, ammonium salt (generic). (a) Chemical substance and significant new uses subject to reporting. (1... with aminonaphthalenesulfonic acid derivative, ammonium salt (PMN P-02-514) is subject to...

  8. 40 CFR 721.10039 - Diethoxybenzenamine derivative, diazotized, coupled with aminonaphthalenesulfonic acid derivative...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ..., diazotized, coupled with aminonaphthalenesulfonic acid derivative, ammonium salt (generic). 721.10039 Section... derivative, ammonium salt (generic). (a) Chemical substance and significant new uses subject to reporting. (1... with aminonaphthalenesulfonic acid derivative, ammonium salt (PMN P-02-514) is subject to...

  9. Bioconversion of cinnamic acid derivatives by Schizophyllum commune.

    PubMed

    Nimura, Yoshifumi; Tsujiyama, Sho-ichi; Ueno, Masayoshi

    2010-10-01

    To investigate the production of useful phenols from plant resources, we examined the metabolism of cinnamic acid derivatives by a wood-rotting fungus, Schizophyllum commune. Four cinnamic acid derivatives (cinnamic, p-coumaric, ferulic, and sinapic acids) were tested as substrates. Two main reactions, reduction and cleavage of the side chain, were observed. Reduction of the side chain was confirmed in cinnamic acid and p-coumaric acid metabolism. The side chain cleavage occurred in p-coumaric acid and ferulic acid metabolism but the initial reactions of these acids differed. Sinapic acid was not metabolized by S. commune. p-Hydroxybenzaldehyde accumulation was observed in the culture to which p-coumaric acid was added. This suggests that S. commune is a useful agent for transforming p-coumaric acid into p-hydroxybenzaldehyde.

  10. Cinnamic acid derivatives as anticancer agents-a review.

    PubMed

    De, P; Baltas, M; Bedos-Belval, F

    2011-01-01

    Cinnamic acid and its phenolic analogues are natural substances. Chemically, in cinnamic acids the 3-phenyl acrylic acid functionality offers three main reactive sites; substitution at the phenyl ring, addition at the α,β- unsaturation and the reactions of the carboxylic acid functionality. Owing to these chemical aspects cinnamic acid derivatives received much attention in medicinal research as traditional as well as recent synthetic antitumor agents. We observed that in spite of their rich medicinal tradition, cinnamic acid derivatives and their anticancer potentials remained underutilized for several decades since the first published clinical use in 1905. In last two decades, there has been huge attention towards various cinnamoyl derivatives and their antitumor efficacy. This review provides a comprehensive and unprecedented literature compilation concerning the synthesis and biological evaluation of various cinnamoyl acids, esters, amides, hydrazides and related derivatives in anticancer research. We envisage that our effort in this review contributes a much needed and timely addition to the literature of medicinal research.

  11. Acetylcholinesterase inhibitory properties of some benzoic acid derivatives

    NASA Astrophysics Data System (ADS)

    Yildiz, Melike; Kiliç, Deryanur; Ünver, Yaǧmur; Şentürk, Murat; Askin, Hakan; Küfrevioǧlu, Ömer Irfan

    2016-04-01

    Acetylcholinesterase (AChE) hydrolyses the neurotransmitter acetylcholine to acetic acid and choline. AChE inhibitors are used in treatment of several neurodegeneartive disorder and Alzheimer's disease. In the present study, inhibition of AChE with some benzoic acid derivatives were investigated. 3-Chloro-benzoic acid (1), 2-hydroxy-5-sulfobenzoic acid (2), 2-(sulfooxy) benzoic acid (3), 2-hydroxybenzoic acid (4), 2,3-dimethoxybenzoic (5), and 3,4,5-trimethoxybenzoic (6) were calculated IC50 values AChE enzyme. Kinetic investigations showed that similarly to AChE inhibitors. Benzoic acid derivatives (1-6) investigated are encouraging agents which may be used as lead molecules in order to derivative novel AChE inhibitors that might be useful in medical applications.

  12. Enzymatic production of caffeic acid by koji from plant resources containing caffeoylquinic acid derivatives.

    PubMed

    Yoshimoto, Makoto; Kurata-Azuma, Rie; Fujii, Makoto; Hou, De-Xing; Ikeda, Kohji; Yoshidome, Tomohisa; Osako, Miho

    2005-09-01

    The effect of a koji (Aspergillus awamori mut.) extract on the caffeoylquinic acid derivatives purified from sweetpotato (Ipomoea batatas L.) leaves was examined to develop the mass production of caffeic acid. A koji extract hydrolyzed the caffeoylquinic acid derivatives, chlorogenic acid, 3,4-di-O-caffeoylquinic acid, 3,5-di-O-caffeoylquinic acid, 4,5-di-O-caffeoylquinic acid and 3,4,5-tri-O-caffeoylquinic acid, to caffeic acid. Furthermore, the koji extract also converted the major polyphenolic components from sweetpotato, burdock (Arctium lappa L.), and mugwort (Artemisia indica var. maximowiczii) leaves to caffeic acid. These results suggest that the production of caffeic acid from plant resources containing caffeoylquinic acid derivatives is possible.

  13. [Phenolic acid derivatives from Alchornea trewioides].

    PubMed

    Qin, Ri-Dong; Cheng, Wei; Zhang, Qing-Ying; Liang, Hong

    2012-07-01

    To study the chemical constituents of Alchornea trewioides, silica gel column chromatography, Sephadex LH-20, reverse phase ODS column chromatography, MCI and semi-preparative HPLC were used to separate the 95% EtOH extract of the root of Alchornea trewioides. The structures were elucidated on the basis of spectroscopic studies including ESI-TOF-MS, 1H NMR, 13C NMR, HSQC and HMBC. Eight phenolic acids were obtained and identified as 1-O-galloyl-6-O-vanilloyl-beta-glucose (1), gallic acid (2), ethyl gallate (3), syringic acid (4), glucosyringic acid (5), erigeside C (6), 3, 4-dimethoxyphenyl-(6'-O-alpha-L-rhamnosyl)-beta-D-glucopyranoside (7) and 3, 4, 5-trimethoxyphenyl-(6'-O-galloyl)-O-beta-D-glucopyranoside (8). Among them, compound 1 is a new compound, compounds 4-8 are isolated from the genus Alchornea for the first time, and the others are isolated from the plant for the first time.

  14. Natural cinnamic acids, synthetic derivatives and hybrids with antimicrobial activity.

    PubMed

    Guzman, Juan David

    2014-11-25

    Antimicrobial natural preparations involving cinnamon, storax and propolis have been long used topically for treating infections. Cinnamic acids and related molecules are partly responsible for the therapeutic effects observed in these preparations. Most of the cinnamic acids, their esters, amides, aldehydes and alcohols, show significant growth inhibition against one or several bacterial and fungal species. Of particular interest is the potent antitubercular activity observed for some of these cinnamic derivatives, which may be amenable as future drugs for treating tuberculosis. This review intends to summarize the literature data on the antimicrobial activity of the natural cinnamic acids and related derivatives. In addition, selected hybrids between cinnamic acids and biologically active scaffolds with antimicrobial activity were also included. A comprehensive literature search was performed collating the minimum inhibitory concentration (MIC) of each cinnamic acid or derivative against the reported microorganisms. The MIC data allows the relative comparison between series of molecules and the derivation of structure-activity relationships.

  15. Piperazic acid derivatives inhibit Gli1 in Hedgehog signaling pathway.

    PubMed

    Khatra, Harleen; Kundu, Jayanta; Khan, Pragya Paramita; Duttagupta, Indranil; Pattanayak, Sankha; Sinha, Surajit

    2016-09-15

    Piperazic acid, a non-proteinogenic amino acid, found in complex secondary metabolites and peptide natural substances, has shown down regulation of Gli1 expression in Hedgehog signaling pathway in cell based assays. Further structure activity relationship study indicated that amide derivatives of piperazic acid are more potent than piperazic acid itself, with little to no toxicity. However, other cellular components involved in the pathway were not affected. To the best of our knowledge, this is the first report on the inhibitory property of piperazic acid in this pathway. Hence, this molecule could serve as a useful tool for studying Hedgehog signaling. PMID:27528433

  16. Caffeic Acid Derivatives in Dried Lamiaceae and Echinacea purpurea Products

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The concentrations of caffeic acid derivatives within Lamiaceae and Echinacea (herb, spice, tea, and dietary supplement forms) readily available in the U.S. marketplace (n=72) were determined. After the first identification of chicoric acid in Ocimum basilicum (basil), the extent to which chicoric a...

  17. Historical aspects and applications of barbituric acid derivatives. A review.

    PubMed

    Guillén Sans, R; Guzmán Chozas, M

    1988-12-01

    This review considers the pharmacological and other applications of barbituric and 2-thiobarbituric acid derivatives. A chronological description about the discovery, structural studies and first clinical assays are given. Therapeutic expectations as anticonvulsant, antimicrobial, spasmolytic, antiinflammatory, antitumoral and some other effects of 5,5-disubstituted barbituric acids and alkylidene- or arylidenebarbituric acids are overviewed. A considerable amount of these types of compounds have been proposed as industrial dyes and pigments, photosensitizers and thermosensitive materials. PMID:3073393

  18. Synthesis and biological evaluation of novel lipoamino acid derivatives.

    PubMed

    Kaki, Shiva Shanker; Arukali, Sammaiah; Korlipara, Padmaja V; Prasad, R B N; Yedla, Poornachandra; Ganesh Kumar, C

    2016-01-01

    Seven novel lipoamino acid conjugates were synthesized from methyl oleate and amino acids. Methyl oleate was grafted to different amino acids using thioglycolic acid as a spacer group. Seven derivatives (3a-g) were prepared and characterized by spectral data (NMR, IR and MS spectral studies). All the derivatives were studied for their antimicrobial, anti-biofilm and anticancer activities. Among all the derivatives, it was found that compound 3b was the most potent antibacterial compound which showed good activity against four Gram positive bacterial strains and also exhibited excellent antifungal activity against a fungal strain. In the anti-biofilm assay, compound 3b showed promising activity with IC50 value of 2.8μM against Bacillus subtilis MTCC 121. All the compounds showed anticancer activities with 3c showing promising anticancer activity (IC50=15.3-22.4μM) against the four cell lines tested. PMID:26586599

  19. Catalytic conversion of lactic acid and its derivatives

    SciTech Connect

    Kokitkar, P.B.; Langford, R.; Miller, D.J.; Jackson, J.E.

    1993-12-31

    The catalytic upgrading of lactic acid and methyl lactate is being investigated. With the commercialization of inexpensive starch fermentation technologies, US production of lactic acid is undergoing a surge. Dropping cost and increased availability offer a major opportunity to develop lactic acid as a renewable feedstock for chemicals production. IT can be catalytically converted into several important chemical intermediates currently derived from petroleum including acrylic acid, propanoic acid, and 2,3-pentanedione. The process can expand the potential of biomass as a substitute feedstock for petroleum and can benefit both the US chemical process industry and US agriculture via increased production of high-value, non-food products from crops and crop byproducts. Reaction studies of lactic acid and its ester are conducted in fixed bed reactors at 250-380{degrees}C and 0.1-0.5 MPa (1-5 atm) using salt catalysts on low surface area supports. Highest selectivities achieved are 42% to acrylic acid and 55% to 2,3-pentanedione from lactic acid over NaNO{sub 3} catalyst on low surface area silica support. High surface area (microporous) or highly acidic supports promote fragmentation to acetaldehyde and thus reduce yields of desirable products. The support acidity gives rice to lactic acid from neat methyl lactate feed but the lactic acid yield goes down after the nitrate salt is impregnated on the support. Both lactic acid and methyl lactate form 2,3-pentanedione. Methyl lactate reactions are more complex since it forms all the products obtained from lactic acid as well as many corresponding esters of the acids obtained from lactic acid (mainly methyl acrylate, methyl propionate, methyl acetate). At high temperatures, methyl acetate and acetic acid yields become significant from methyl lactate whereas lactic acid gives significant amount of acetol at high temperatures.

  20. Joint action of benzoxazinone derivatives and phenolic acids.

    PubMed

    Jia, Chunhong; Jia, Chunghong; Kudsk, Per; Mathiassen, Solvejg K

    2006-02-22

    The joint action of binary and ternary mixtures of benzoxazinone derivatives and phenolic acids was studied using the additive dose model (ADM) as reference model. The activity of fixed-ratio mixtures of phenolic acids [ferulic acid (FA), p-coumaric acid (CA), vanillic acid (VA), and p-hydroxybenzoic acid (HBA)] and benzoxazinone derivatives [2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA), 6-methoxybenzoxazolin-2-one (MBOA), benzoxazolin-2-one (BOA), 2-aminophenol (AP), and N-(2-hydroxyphenyl)acetamide (HPAA)] on Lolium perenne and Myosotis arvensis root growth was assessed in Petri dishes. Root length was recorded 6 days after seeding, and EC(50) and EC(90) values were estimated using nonlinear regression analyses. The benzoxazinone derivatives were found to be more phytotoxic than the phenolic acids, particularly on M. arvensis. Binary mixtures of phenolic acids responded predominantly additively on both plant species. Deviations from additivity were species-specific with antagonistic responses on L. perenne and synergistic responses on M. arvensis. Similarly, binary mixtures of benzoxazinone derivatives also followed the ADM, although synergistic responses were observed for BOA + AP and BOA + HPAA. Binary and ternary mixtures of benzoxazinone derivatives and phenolic acids responded primarily antagonistically; however, a significant synergistic performance was observed with DIMBOA + FA and DIMBOA + VA on L. perenne. These results do not support the assumption that allelopathic effects of wheat can be attributed to synergistic effects of otherwise weakly active allelopathic compounds, and it is suggested that future research be directed toward identifying and studying the effects of other potential allelochemicals including the degradation products of the most abundant wheat allelochemicals.

  1. Oleanolic acid and related derivatives as medicinally important compounds.

    PubMed

    Sultana, Nighat; Ata, Athar

    2008-12-01

    Oleanolic acid has been isolated from chloroform extract of Olea ferruginea Royle after removal of organic bases and free acids. The literature survey revealed it to be biologically very important. In this review the biological significance of oleanolic acid and its derivatives has been discussed. The aim of this review is to update current knowledge on oleanolic acid and its natural and semisynthetic analogs, focussing on its cytotoxic, antitumer, antioxidant, anti-inflamatory, anti-HIV, acetyl cholinesterase, alpha-glucosidase, antimicrobial, hepatoprotective, anti-inflammatory, antipruritic, spasmolytic activity, anti-angiogenic, antiallergic, antiviral and immunomodulatory activities. We present in this review, for the first time, a compilation of the most relevant scientific papers and technical reports of the chemical, pre-clinical and clinical research on the properties of oleanolic acid and its derivatives.

  2. Oleanolic acid and related derivatives as medicinally important compounds.

    PubMed

    Sultana, Nighat; Ata, Athar

    2008-12-01

    Oleanolic acid has been isolated from chloroform extract of Olea ferruginea Royle after removal of organic bases and free acids. The literature survey revealed it to be biologically very important. In this review the biological significance of oleanolic acid and its derivatives has been discussed. The aim of this review is to update current knowledge on oleanolic acid and its natural and semisynthetic analogs, focussing on its cytotoxic, antitumer, antioxidant, anti-inflamatory, anti-HIV, acetyl cholinesterase, alpha-glucosidase, antimicrobial, hepatoprotective, anti-inflammatory, antipruritic, spasmolytic activity, anti-angiogenic, antiallergic, antiviral and immunomodulatory activities. We present in this review, for the first time, a compilation of the most relevant scientific papers and technical reports of the chemical, pre-clinical and clinical research on the properties of oleanolic acid and its derivatives. PMID:18618318

  3. Conformational Interconversions of Amino Acid Derivatives.

    PubMed

    Kaminský, Jakub; Jensen, Frank

    2016-02-01

    Exhaustive conformational interconversions including transition structure analyses of N-acetyl-l-glycine-N-methylamide as well as its alanine, serine, and cysteine analogues have been investigated at the MP2/6-31G** level, yielding a total of 142 transition states. Improved estimates of relative energies were obtained by separately extrapolating the Hartree-Fock and MP2 energies to the basis set limit and adding the difference between CCSD(T) and MP2 results with the cc-pVDZ basis set to the extrapolated MP2 results. The performance of eight empirical force fields (AMBER94, AMBER14SB, MM2, MM3, MMFFs, CHARMM22_CMAP, OPLS_2005, and AMOEBAPRO13) in reproducing ab initio energies of transition states was tested. Our results indicate that commonly used class I force fields employing a fixed partial charge model for the electrostatic interaction provide mean errors in the ∼10 kJ/mol range for energies of conformational transition states for amino acid conformers. Modern reparametrized versions, such as CHARMM22_CMAP, and polarizable force fields, such as AMOEBAPRO13, have slightly lower mean errors, but maximal errors are still in the 35 kJ/mol range. There are differences between the force fields in their ability for reproducing conformational transitions classified according to backbone/side-chain or regions in the Ramachandran angles, but the data set is likely too small to draw any general conclusions. Errors in conformational interconversion barriers by ∼10 kJ/mol suggest that the commonly used force field may bias certain types of transitions by several orders of magnitude in rate and thus lead to incorrect dynamics in simulations. It is therefore suggested that information for conformational transition states should be included in parametrizations of new force fields. PMID:26691979

  4. Production of Diethyl Terephthalate from Biomass-Derived Muconic Acid.

    PubMed

    Lu, Rui; Lu, Fang; Chen, Jiazhi; Yu, Weiqiang; Huang, Qianqian; Zhang, Junjie; Xu, Jie

    2016-01-01

    We report a cascade synthetic route to directly obtain diethyl terephthalate, a replacement for terephthalic acid, from biomass-derived muconic acid, ethanol, and ethylene. The process involves two steps: First, a substituted cyclohexene system is built through esterification and Diels-Alder reaction; then, a dehydrogenation reaction provides diethyl terephthalate. The key esterification reaction leads to improved solubility and modulates the electronic properties of muconic acid, thus promoting the Diels-Alder reaction with ethylene. With silicotungstic acid as the catalyst, nearly 100% conversion of muconic acid was achieved, and the cycloadducts were formed with more than 99.0% selectivity. The palladium-catalyzed dehydrogenation reaction preferentially occurs under neutral or mildly basic conditions. The total yield of diethyl terephthalate reached 80.6% based on the amount of muconic acid used in the two-step synthetic process. PMID:26592149

  5. Lipoproteini lipase-derived fatty acids: physiology and dysfunction.

    PubMed

    Lee, Jee; Goldberg, Ira J

    2007-12-01

    Under normal circumstances, most energy substrate used for heart contraction derives from fatty acids in the form of nonesterified fatty acids bound to albumin or fatty acids derived from lipolysis of lipoprotein-bound triglyceride by lipoprotein lipase (LpL). By creating LpL knockout mice (hLpL0), we learned that loss of cardiac LpL leads to myocardial dysfunction; therefore, neither nonesterified fatty acids nor increased glucose metabolism can replace LpL actions. hLpL0 mice do not survive abdominal aortic constriction and they develop more heart failure with hypertension. Conversely, we created a mouse overexpressing cardiomyocyte-anchored LpL. This transgene produced cardiac lipotoxicity and dilated cardiomyopathy. Methods to alter this phenotype and the causes of other models of lipotoxicity are currently being studied and will provide further insight into the physiology of lipid metabolism in the heart. PMID:18367009

  6. Extracting metal ions with diphosphonic acid, or derivative thereof

    DOEpatents

    Horwitz, E.P.; Gatrone, R.C.; Nash, K.L.

    1994-07-26

    Thermodynamically-unstable complexing agents which are diphosphonic acids and diphosphonic acid derivatives (or sulfur containing analogs), like carboxyhydroxymethanediphosphonic acid and vinylidene-1,1-diphosphonic acid, are capable of complexing with metal ions, and especially metal ions in the II, III, IV, V and VI oxidation states, to form stable, water-soluble metal ion complexes in moderately alkaline to highly-acidic media. However, the complexing agents can be decomposed, under mild conditions, into non-organic compounds which, for many purposes are environmentally-nondamaging compounds thereby degrading the complex and releasing the metal ion for disposal or recovery. Uses for such complexing agents as well as methods for their manufacture are also described. 1 fig.

  7. Extracting metal ions with diphosphonic acid, or derivative thereof

    DOEpatents

    Horwitz, Earl P.; Gatrone, Ralph C.; Nash, Kenneth L.

    1994-01-01

    Thermodynamically-unstable complexing agents which are diphosphonic acids and diphosphonic acid derivatives (or sulphur containing analogs), like carboxyhydroxymethanediphosphonic acid and vinylidene-1,1-diphosphonic acid, are capable of complexing with metal ions, and especially metal ions in the II, III, IV, V and VI oxidation states, to form stable, water-soluble metal ion complexes in moderately alkaline to highly-acidic media. However, the complexing agents can be decomposed, under mild conditions, into non-organic compounds which, for many purposes are environmentally-nondamaging compounds thereby degrading the complex and releasing the metal ion for disposal or recovery. Uses for such complexing agents as well as methods for their manufacture are also described.

  8. Membrane extraction with thermodynamically unstable diphosphonic acid derivatives

    DOEpatents

    Horwitz, Earl Philip; Gatrone, Ralph Carl; Nash, Kenneth LaVerne

    1997-01-01

    Thermodynamically-unstable complexing agents which are diphosphonic acids and diphosphonic acid derivatives (or sulphur containing analogs), like carboxyhydroxymethanediphosphonic acid and vinylidene-1,1-diphosphonic acid, are capable of complexing with metal ions, and especially metal ions in the II, III, IV, V and VI oxidation states, to form stable, water-soluble metal ion complexes in moderately alkaline to highly-acidic media. However, the complexing agents can be decomposed, under mild conditions, into non-organic compounds which, for many purposes are environmentally-nondamaging compounds thereby degrading the complex and releasing the metal ion for disposal or recovery. Uses for such complexing agents as well as methods for their manufacture are also described.

  9. Amino acid decarboxylations produced by lipid-derived reactive carbonyls in amino acid mixtures.

    PubMed

    Hidalgo, Francisco J; León, M Mercedes; Zamora, Rosario

    2016-10-15

    The formation of 2-phenylethylamine and phenylacetaldehyde in mixtures of phenylalanine, a lipid oxidation product, and a second amino acid was studied to determine the role of the second amino acid in the degradation of phenylalanine produced by lipid-derived reactive carbonyls. The presence of the second amino acid usually increased the formation of the amine and reduced the formation of the Strecker aldehyde. The reasons for this behaviour seem to be related to the α-amino group and the other functional groups (mainly amino or similar groups) present in the side-chain of the amino acid. These groups are suggested to modify the lipid-derived reactive carbonyl but not the reaction mechanism because the Ea of formation of both 2-phenylethylamine and phenylacetaldehyde remained unchanged in all studied systems. All these results suggest that the amine/aldehyde ratio obtained by amino acid degradation can be modified by adding free amino acids during food formulation.

  10. Simultaneous determination of carminic acid, riboflavine, curcumin and erythrosine by derivative spectrophotometry and ratio spectra derivative.

    PubMed

    Nevado, J J; Cabanillas, C G; Salcedo, A M

    1994-05-01

    A quaternary mixture of carminic acid, riboflavine, curcumin and erythrosine can be resolved with a previous extraction step into metyl-isobutyl ketone and, resolving the binary mixtures obtained in the aqueous phase and organic phase, using derivative spectrophotometry on the basis of the zero-crossing measurements in the first derivative spectra as well as the first derivative of ratio spectra. The conditions of extraction established and the proposed methods have been tested to determine these colorants in several synthetic mixtures of four dyes, obtaining good recoveries. The methods have been applied in yoghurt samples spiked with the dyes. PMID:18966000

  11. Crystal engineering: co-crystals of cinnamic acid derivatives with a pyridyl derivative co-crystallizer.

    PubMed

    Lorenzo, Daniel A; Forrest, Sebastian J K; Sparkes, Hazel A

    2016-02-01

    A number of hydrogen-bonded co-crystals, consisting of a cinnamic acid derivative and a pyridyl co-crystallizer, have been synthesized and their properties investigated by X-ray diffraction. Samples were prepared by recrystallization or solvent drop grinding of trans-cinnamic acid (1), 4-methylcinnamic acid (2), 4-methoxy cinnamic acid (3) or 3,4-methoxy cinnamic acid (4), with 4,4-dipyridyl (A), iso-nicotinamide (B) or nicotinamide (C). The X-ray single-crystal structures of seven novel co-crystals, obtained through recrystallization, are examined and the hydrogen-bonding interactions discussed. Consistent hydrogen-bonding motifs were observed for samples prepared when using 4,4-dipyridyl (A) or iso-nicotinamide (B) as the co-crystallizing agent. Powder X-ray diffraction analysis of the samples prepared by solvent drop grinding suggests the formation of ten co-crystals.

  12. Synthesis of kojic acid derivatives as secondary binding site probes of D-amino acid oxidase

    PubMed Central

    Raje, Mithun; Hin, Niyada; Duvall, Bridget; Ferraris, Dana V.; Berry, James F.; Thomas, Ajit G.; Alt, Jesse; Rojas, Camilo; Slusher, Barbara S.; Tsukamoto, Takashi

    2013-01-01

    A series of kojic acid (5-hydroxy-2-hydroxymethyl-4H-pyran-4-one) derivatives were synthesized and tested for their ability to inhibit D-amino acid oxidase (DAAO). Various substituents were incorporated into kojic acid at its 2-hydroxymethyl group. These analogs serve as useful molecular probes to explore the secondary binding site, which can be exploited in designing more potent DAAO inhibitors. PMID:23683589

  13. Hydroxybenzoic acids and their derivatives as peroxynitrite scavengers.

    PubMed

    Hubková, Beáta; Veliká, Beáta; Birková, Anna; Guzy, Juraj; Mareková, Mária

    2014-10-01

    A social challenge of the 21(st) century is to reduce the incidence of chronic diseases. A balanced diet rich in polyphenols could contribute to reduce the risk and to the prevention of diabetes, coronary heart disease, cancer, Alzheimer's diseases and cataract(1). Hydroxybenzoic acids (HBA) and their derivatives, which are one of the substances responsible for these beneficial properties, are known mainly due to their antioxidant properties(2). They are effective scavengers of free radicals and reactive nitrogen species, such as peroxynitrite. Peroxynitrite is resulting from the reaction of nitric oxide with superoxide, causes lipid peroxidation and subsequent cellular damage and is responsible for the inactivation of many enzymes, activation of stress signalling pathways, release of proapoptotic factors, as well as cardiovascular dysfunction in septic schock(3). In this study we have tested 2-HBA, 3-HBA, 4-HBA, acetylsalicylic acid, 4-HBA methyl and propyl esters, 2,3-dihydroxybenzoic acid (DHBA), 2,5-DHBA, 2,4-DHBA, 2,6-DHBA, 3,5-DHBA, 3,4-DHBA, gallic acid and caffeic acid, by UV/VIS spectroscopy. The best ability to scavenge peroxynitrite was observed for gallic acid, 2,4-DHBA, 3,5-DHBA and caffeic acid. Improved comprehension of the complex relationship between the antioxidant properties of substances and their structure is important to understand their proper use in the prevention and treatment of diseases and for the detection of pathological processes. Monitoring and improved understanding of the antioxidant properties of hydroxybenzoic acid derivatives are important due to their frequent use in modern medical nutrition therapies.

  14. Biological Activities of Oleanolic Acid Derivatives from Calendula officinalis Seeds.

    PubMed

    Zaki, Ahmed; Ashour, Ahmed; Mira, Amira; Kishikawa, Asuka; Nakagawa, Toshinori; Zhu, Qinchang; Shimizu, Kuniyoshi

    2016-05-01

    Phytochemical examination of butanol fraction of Calendula officinalis seeds led to the isolation of two compounds identified as 28-O-β-D-glucopyranosyl-oleanolic acid 3-O-β-D-glucopyranosyl (1→3)-β-D-glucopyranosiduronic acid (CS1) and oleanolic acid 3-O-β-D-glucopyranosyl (1→3)-β-D-glucopyranosiduronic acid (CS2). Biological evaluation was carried out for these two compounds such as melanin biosynthesis inhibitory, hyaluronic acid production activities, anti obesity using lipase inhibition and adipocyte differentiation as well as evaluation of the protective effect against hydrogen peroxide induced neurotoxicity in neuro-2A cells. The results showed that, compound CS2 has a melanin biosynthesis stimulatory activity; however, compound CS1 has a potent stimulatory effect for the production of hyaluronic acid on normal human dermal fibroblast from adult (NHDF-Ad). Both compounds did not show any inhibitory effect on both lipase and adipocyte differentiation. Compound CS2 could protect neuro-2A cells and increased cell viability against H2 O2 . These activities (melanin biosynthesis stimulatory and protective effect against H2 O2 of CS2 and hyaluronic acid productive activities of these triterpene derivatives) have been reported for the first time. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26887328

  15. Biological Activities of Oleanolic Acid Derivatives from Calendula officinalis Seeds.

    PubMed

    Zaki, Ahmed; Ashour, Ahmed; Mira, Amira; Kishikawa, Asuka; Nakagawa, Toshinori; Zhu, Qinchang; Shimizu, Kuniyoshi

    2016-05-01

    Phytochemical examination of butanol fraction of Calendula officinalis seeds led to the isolation of two compounds identified as 28-O-β-D-glucopyranosyl-oleanolic acid 3-O-β-D-glucopyranosyl (1→3)-β-D-glucopyranosiduronic acid (CS1) and oleanolic acid 3-O-β-D-glucopyranosyl (1→3)-β-D-glucopyranosiduronic acid (CS2). Biological evaluation was carried out for these two compounds such as melanin biosynthesis inhibitory, hyaluronic acid production activities, anti obesity using lipase inhibition and adipocyte differentiation as well as evaluation of the protective effect against hydrogen peroxide induced neurotoxicity in neuro-2A cells. The results showed that, compound CS2 has a melanin biosynthesis stimulatory activity; however, compound CS1 has a potent stimulatory effect for the production of hyaluronic acid on normal human dermal fibroblast from adult (NHDF-Ad). Both compounds did not show any inhibitory effect on both lipase and adipocyte differentiation. Compound CS2 could protect neuro-2A cells and increased cell viability against H2 O2 . These activities (melanin biosynthesis stimulatory and protective effect against H2 O2 of CS2 and hyaluronic acid productive activities of these triterpene derivatives) have been reported for the first time. Copyright © 2016 John Wiley & Sons, Ltd.

  16. Synthesis, antimicrobial evaluation and QSAR studies of stearic acid derivatives.

    PubMed

    Tahlan, S; Kumar, P; Narasimhan, B

    2014-02-01

    A series of Schiff bases (1-17) and esters (18-28) of stearic acid was synthesized and characterized by physicochemical as well as spectral means. The synthesized compounds were evaluated in vitro for their antimicrobial activity by tube dilution method. The antimicrobial screening results indicated that the compounds having electron releasing groups on benzylidene nucleus were found to be more active against bacterial strains and compounds having electron withdrawing groups on benzylidene nucleus were found to be more active against fungal strains. QSAR studies demonstrated that electronic parameters dipole moment (µ) and total energy (Te) were the most important descriptors in describing the antimicrobial activity of synthesized stearic acid derivatives.

  17. [Cardioprotective properties of new glutamic acid derivative under stress conditions].

    PubMed

    Perfilova, V N; Sadikova, N V; Berestovitskaia, V M; Vasil'eva, O S

    2014-01-01

    The effect of new glutamic acid derivative on the cardiac ino- and chronotropic functions has been studied in experiments on rats exposed to 24-hour immobilization-and-pain stress. It is established that glutamic acid derivative RGPU-238 (glufimet) at a dose of 28.7 mg/kg increases the increment of myocardial contractility and relaxation rates and left ventricular pressure in stress-tested animals by 13 1,1, 72.4, and 118.6%, respectively, as compared to the control group during the test for adrenoreactivity. Compound RGPU-238 increases the increment of the maximum intensity of myocardium functioning by 196.5 % at 30 sec of isometric workload as compared to the control group. The cardioprotective effect of compound RGPU-238 is 1.5 - 2 times higher than that of the reference drug phenibut.

  18. Microbial production of fatty acid-derived fuels and chemicals

    PubMed Central

    Lennen, Rebecca M; Pfleger, Brian F

    2013-01-01

    Fatty acid metabolism is an attractive route to produce liquid transportation fuels and commodity oleochemicals from renewable feedstocks. Recently, genes and enzymes, which comprise metabolic pathways for producing fatty acid-derived compounds (e.g. esters, alkanes, olefins, ketones, alcohols, polyesters) have been elucidated and used in engineered microbial hosts. The resulting strains often generate products at low percentages of maximum theoretical yields, leaving significant room for metabolic engineering. Economically viable processes will require strains to approach theoretical yields, particularly for replacement of petroleum-derived fuels. This review will describe recent progress toward this goal, highlighting the scientific discoveries of each pathway, ongoing biochemical studies to understand each enzyme, and metabolic engineering strategies that are being used to improve strain performance. PMID:23541503

  19. Gastroprotective effect and cytotoxicity of carnosic acid derivatives.

    PubMed

    Theoduloz, Cristina; Pertino, Mariano Walter; Rodríguez, Jaime A; Schmeda-Hirschmann, Guillermo

    2011-06-01

    Carnosic acid (CA) is the main phenolic diterpene of rosemary (Rosmarinus officinalis L., Lamiaceae) and presents gastroprotective effect in vitro and in vivo. To determine structure-activity relationships, seventeen esters and ethers of CA were prepared, comprising aliphatic, aromatic, and heterocyclic compounds. The naturally occurring 12-O-methylcarnosic acid (14) was also included in the study. The compounds were evaluated for their gastroprotective activity in the HCl/EtOH-induced gastric lesions model in mice, and for cytotoxicity in human adenocarcinoma AGS cells, Hep G2 hepatocellular carcinoma cells, and human lung fibroblasts. At 10 mg/kg, some of the CA derivatives (5, 8, 9, 12, 14, and 18) were more effective preventing gastric lesions than the reference compound lansoprazole at the same dose. The dibenzoate 9, diindoleacetate 12, and the derivative 18 showed the best gastroprotective effect combined with the lowest cytotoxicity.

  20. Gastroprotective effect and cytotoxicity of carnosic acid derivatives.

    PubMed

    Theoduloz, Cristina; Pertino, Mariano Walter; Rodríguez, Jaime A; Schmeda-Hirschmann, Guillermo

    2011-06-01

    Carnosic acid (CA) is the main phenolic diterpene of rosemary (Rosmarinus officinalis L., Lamiaceae) and presents gastroprotective effect in vitro and in vivo. To determine structure-activity relationships, seventeen esters and ethers of CA were prepared, comprising aliphatic, aromatic, and heterocyclic compounds. The naturally occurring 12-O-methylcarnosic acid (14) was also included in the study. The compounds were evaluated for their gastroprotective activity in the HCl/EtOH-induced gastric lesions model in mice, and for cytotoxicity in human adenocarcinoma AGS cells, Hep G2 hepatocellular carcinoma cells, and human lung fibroblasts. At 10 mg/kg, some of the CA derivatives (5, 8, 9, 12, 14, and 18) were more effective preventing gastric lesions than the reference compound lansoprazole at the same dose. The dibenzoate 9, diindoleacetate 12, and the derivative 18 showed the best gastroprotective effect combined with the lowest cytotoxicity. PMID:21246485

  1. Synthesis and antifungal activity of bile acid-derived oxazoles.

    PubMed

    Fernández, Lucía R; Svetaz, Laura; Butassi, Estefanía; Zacchino, Susana A; Palermo, Jorge A; Sánchez, Marianela

    2016-04-01

    Peracetylated bile acids (1a-g) were used as starting materials for the preparation of fourteen new derivatives bearing an oxazole moiety in their side chain (6a-g, 8a-g). The key step for the synthetic path was a Dakin-West reaction followed by a Robinson-Gabriel cyclodehydration. A simpler model oxazole (12) was also synthesized. The antifungal activity of the new compounds (6a-g) as well as their starting bile acids (1a-g) was tested against Candida albicans. Compounds 6e and 6g showed the highest percentages of inhibition (63.84% and 61.40% at 250 μg/mL respectively). Deacetylation of compounds 6a-g, led to compounds 8a-g which showed lower activities than the acetylated derivatives. PMID:26827629

  2. Quantification of acidic compounds in complex biomass-derived streams

    SciTech Connect

    Karp, Eric M.; Nimlos, Claire T.; Deutch, Steve; Salvachúa, Davinia; Cywar, Robin M.; Beckham, Gregg T.

    2016-01-01

    Biomass-derived streams that contain acidic compounds from the degradation of lignin and polysaccharides (e.g. black liquor, pyrolysis oil, pyrolytic lignin, etc.) are chemically complex solutions prone to instability and degradation during analysis, making quantification of compounds within them challenging. Here we present a robust analytical method to quantify acidic compounds in complex biomass-derived mixtures using ion exchange, sample reconstitution in pyridine and derivatization with BSTFA. The procedure is based on an earlier method originally reported for kraft black liquors and, in this work, is applied to identify and quantify a large slate of acidic compounds in corn stover derived alkaline pretreatment liquor (APL) as a function of pretreatment severity. Analysis of the samples is conducted with GCxGC-TOFMS to achieve good resolution of the components within the complex mixture. The results reveal the dominant low molecular weight components and their concentrations as a function of pretreatment severity. Application of this method is also demonstrated in the context of lignin conversion technologies by applying it to track the microbial conversion of an APL substrate. Here too excellent results are achieved, and the appearance and disappearance of compounds is observed in agreement with the known metabolic pathways of two bacteria, indicating the sample integrity was maintained throughout analysis. Finally, it is shown that this method applies more generally to lignin-rich materials by demonstrating its usefulness in analysis of pyrolysis oil and pyrolytic lignin.

  3. Citric-acid-derived photo-cross-linked biodegradable elastomers.

    PubMed

    Gyawali, Dipendra; Tran, Richard T; Guleserian, Kristine J; Tang, Liping; Yang, Jian

    2010-01-01

    Citric-acid-derived thermally cross-linked biodegradable elastomers (CABEs) have recently received significant attention in various biomedical applications, including tissue-engineering orthopedic devices, bioimaging and implant coatings. However, citric-acid-derived photo-cross-linked biodegradable elastomers are rarely reported. Herein, we report a novel photo-cross-linked biodegradable elastomer, referred to as poly(octamethylene maleate citrate) (POMC), which preserves pendant hydroxyl and carboxylic functionalities after cross-linking for the potential conjugation of biologically active molecules. Pre-POMC is a low-molecular-mass pre-polymer with an average molecular mass between 701 and 1291 Da. POMC networks are soft and elastic with an initial modulus of 0.07 to 1.3 MPa and an elongation-at-break between 38 and 382%. FT-IR-ATR results confirmed the successful surface immobilization of type-I collagen onto POMC films, which enhanced in vitro cellular attachment and proliferation. Photo-polymerized POMC films implanted subcutaneously into Sprague-Dawley rats demonstrated minimal in vivo inflammatory responses. The development of POMC enriches the family of citric-acid-derived biodegradable elastomers and expands the available biodegradable polymers for versatile needs in biomedical applications.

  4. Citric-Acid-Derived Photo-cross-Linked Biodegradable Elastomers

    PubMed Central

    Gyawali, Dipendra; Tran, Richard T.; Guleserian, Kristine J.; Tang, Liping; Yang, Jian

    2010-01-01

    Citric-acid-derived thermally cross-linked biodegradable elastomers (CABEs) have recently received significant attention in various biomedical applications, including tissue-engineering orthopedic devices, bioimaging and implant coatings. However, citric-acid-derived photo-cross-linked biodegradable elastomers are rarely reported. Herein, we report a novel photo-cross-linked biodegradable elastomer, referred to as poly(octamethylene maleate citrate) (POMC), which preserves pendant hydroxyl and carboxylic functionalities after cross-linking for the potential conjugation of biologically active molecules. POMC is a low-molecular-mass pre-polymer with a molecular mass average between 701 and 1291 Da. POMC networks are soft and elastic with an initial modulus of 0.07 to 1.3 MPa and an elongation at break between 38 and 382%. FT-IR–ATR results confirmed the successful surface immobilization of type-I collagen onto POMC films, which enhanced in vitro cellular attachment and proliferation. Photo-polymerized POMC films implanted subcutaneously into Sprague–Dawley rats demonstrated minimal in vivo inflammatory responses. The development of POMC enriches the family of citric-acid-derived biodegradable elastomers and expands the available biodegradable polymers for versatile needs in biomedical applications. PMID:20557687

  5. Interactions of salicylic acid derivatives with calcite crystals.

    PubMed

    Ukrainczyk, Marko; Gredičak, Matija; Jerić, Ivanka; Kralj, Damir

    2012-01-01

    Investigation of basic interactions between the active pharmaceutical compounds and calcium carbonates is of great importance because of the possibility to use the carbonates as a mineral carrier in drug delivery systems. In this study the mode and extent of interactions of salicylic acid and its amino acid derivates, chosen as pharmaceutically relevant model compounds, with calcite crystals are described. Therefore, the crystal growth kinetics of well defined rhombohedral calcite seed crystals in the systems containing salicylic acid (SA), 5-amino salicylic acid (5-ASA), N-salicyloil-l-aspartic acid (N-Sal-Asp) or N-salicyloil-l-glutamic acid (N-Sal-Glu), were investigated. The precipitation systems were of relatively low initial supersaturation and of apparently neutral pH. The data on the crystal growth rate reductions in the presence of the applied salicylate molecules were analyzed by means of Cabrera & Vermileya's, and Kubota & Mullin's models of interactions of the dissolved additives and crystal surfaces. The crystal growth kinetic experiments were additionally supported with the appropriate electrokinetic, spectroscopic and adsorption measurements. The Langmuir adsorption constants were determined and they were found to be in a good correlation with values obtained from crystal growth kinetic analyses. The results indicated that salicylate molecules preferentially adsorb along the steps on the growing calcite surfaces. The values of average spacing between the adjacent salicylate adsorption active sites and the average distance between the neighboring adsorbed salicylate molecules were also estimated. PMID:21963207

  6. Interactions of salicylic acid derivatives with calcite crystals.

    PubMed

    Ukrainczyk, Marko; Gredičak, Matija; Jerić, Ivanka; Kralj, Damir

    2012-01-01

    Investigation of basic interactions between the active pharmaceutical compounds and calcium carbonates is of great importance because of the possibility to use the carbonates as a mineral carrier in drug delivery systems. In this study the mode and extent of interactions of salicylic acid and its amino acid derivates, chosen as pharmaceutically relevant model compounds, with calcite crystals are described. Therefore, the crystal growth kinetics of well defined rhombohedral calcite seed crystals in the systems containing salicylic acid (SA), 5-amino salicylic acid (5-ASA), N-salicyloil-l-aspartic acid (N-Sal-Asp) or N-salicyloil-l-glutamic acid (N-Sal-Glu), were investigated. The precipitation systems were of relatively low initial supersaturation and of apparently neutral pH. The data on the crystal growth rate reductions in the presence of the applied salicylate molecules were analyzed by means of Cabrera & Vermileya's, and Kubota & Mullin's models of interactions of the dissolved additives and crystal surfaces. The crystal growth kinetic experiments were additionally supported with the appropriate electrokinetic, spectroscopic and adsorption measurements. The Langmuir adsorption constants were determined and they were found to be in a good correlation with values obtained from crystal growth kinetic analyses. The results indicated that salicylate molecules preferentially adsorb along the steps on the growing calcite surfaces. The values of average spacing between the adjacent salicylate adsorption active sites and the average distance between the neighboring adsorbed salicylate molecules were also estimated.

  7. Urease inhibitory activities of β-boswellic acid derivatives

    PubMed Central

    2013-01-01

    Background and the purpose of the study Boswellia carterii have been used in traditional medicine for many years for management different gastrointestinal disorders. In this study, we wish to report urease inhibitory activity of four isolated compound of boswellic acid derivative. Methods 4 pentacyclic triterpenoid acids were isolated from Boswellia carterii and identified by NMR and Mass spectroscopic analysis (compounds 1, 3-O-acetyl-9,11-dehydro-β-boswellic acid; 2, 3-O-acetyl-11-hydroxy-β-boswellic acid; 3. 3-O- acetyl-11-keto-β-boswellic acid and 4, 11-keto-β-boswellic acid. Their inhibitory activity on Jack bean urease were evaluated. Docking and pharmacophore analysis using AutoDock 4.2 and Ligandscout 3.03 programs were also performed to explain possible mechanism of interaction between isolated compounds and urease enzyme. Results It was found that compound 1 has the strongest inhibitory activity against Jack bean urease (IC50 = 6.27 ± 0.03 μM), compared with thiourea as a standard inhibitor (IC50 = 21.1 ± 0.3 μM). Conclusion The inhibition potency is probably due to the formation of appropriate hydrogen bonds and hydrophobic interactions between the investigated compounds and urease enzyme active site and confirms its traditional usage. PMID:23351363

  8. Evaluation of antioxidant properties of monoaromatic derivatives of pulvinic acids.

    PubMed

    Habrant, Damien; Poigny, Stéphane; Ségur-Derai, Muriel; Brunel, Yves; Heurtaux, Benoît; Le Gall, Thierry; Strehle, Axelle; Saladin, Régis; Meunier, Stéphane; Mioskowski, Charles; Wagner, Alain

    2009-04-23

    The natural mushroom pigment Norbadione A and three other pulvinic acids were shown by our group to display very efficient antioxidant properties by comparison with a collection of potent molecules including catechols, flavonoids, stilbenes, or coumarins. Despite numerous publications on robust and straightforward synthetic access to pulvinic acids by us and others, no report has been made to unravel the structure-activity relationships that govern the striking antioxidant activity. Herein is presented the synthesis of 18 diverse pulvinic acid derivatives and the study of their radical scavenging capacities by four different assays. The influence of each of the two phenyl rings, of their substituents and of the lateral chain on the antioxidant properties, was explored to reveal a simplified structure of excellent activity. These results, along with the absence of cytotoxicity, make the synthesized compounds interesting to evaluate for several biological activities and especially for anti-inflammatory effects and skin protection against UV induced oxidative stress.

  9. Synthesis and properties of synthetic fulvic acid derived from hematoxylin

    NASA Astrophysics Data System (ADS)

    Litvin, Valentina A.; Minaev, Boris F.; Baryshnikov, Gleb V.

    2015-04-01

    A model fulvic acid (FA) was synthesized from a natural dye, hematoxylin, in a slow oxidative polymerization/condensation reaction catalysed by OH- at pH ca. 12. The resulting dark-brown product, acidified to pH ca. 2, did not precipitate from the reaction solution. It was isolated and purified by cation-exchange resin. Its physicochemical and spectroscopic properties, as determined by means of elemental analysis, molecular weight analyses, Fourier transform infra red (FTIR) and ultraviolet-visible (UV-VIS) spectroscopy, X-ray diffraction and electron paramagnetic resonance (EPR) spectroscopy, showed a close resemblance to natural FA. The similarity and differences between synthetic fulvic acids derived from hematoxylin and the natural fulvic acids substances are discussed. Quantum-chemical calculations of the supposed primary oxidation products of hematoxylin are performed and compared with observations.

  10. Template directed reactions of 2-aminoadenylic acid derivatives

    NASA Technical Reports Server (NTRS)

    Webb, T. R.; Orgel, L. E.

    1982-01-01

    The template-directed oligomerization of activated derivatives of 2-aminoadenylic acid (paA) on polyuridylic acid (poly(U)) in aqueous buffers was studied. The reaction differs from that of adenylic acid (pA) under identical conditions, in that only di- and tri-nucleotides are observed as substantial products rather than a longer sequence of oligomers. The reaction of paA also differs from that of pA in that it does not require Mg (2+), and is less susceptible to increased temperature. The relevance of these observations to the chemical evolution of polynucleotide replication is discussed. Improved syntheses of paA and its diphosphate are reported.

  11. Starch Modification by Organic Acids and Their Derivatives: A Review.

    PubMed

    Ačkar, Đurđica; Babić, Jurislav; Jozinović, Antun; Miličević, Borislav; Jokić, Stela; Miličević, Radoslav; Rajič, Marija; Šubarić, Drago

    2015-10-27

    Starch has been an inexhaustible subject of research for many decades. It is an inexpensive, readily-available material with extensive application in the food and processing industry. Researchers are continually trying to improve its properties by different modification procedures and expand its application. What is mostly applied in this view are their chemical modifications, among which organic acids have recently drawn the greatest attention, particularly with respect to the application of starch in the food industry. Namely, organic acids naturally occur in many edible plants and many of them are generally recognized as safe (GRAS), which make them ideal modification agents for starch intended for the food industry. The aim of this review is to give a short literature overview of the progress made in the research of starch esterification, etherification, cross-linking, and dual modification with organic acids and their derivatives.

  12. Plant amino acid-derived vitamins: biosynthesis and function.

    PubMed

    Miret, Javier A; Munné-Bosch, Sergi

    2014-04-01

    Vitamins are essential organic compounds for humans, having lost the ability to de novo synthesize them. Hence, they represent dietary requirements, which are covered by plants as the main dietary source of most vitamins (through food or livestock's feed). Most vitamins synthesized by plants present amino acids as precursors (B1, B2, B3, B5, B7, B9 and E) and are therefore linked to plant nitrogen metabolism. Amino acids play different roles in their biosynthesis and metabolism, either incorporated into the backbone of the vitamin or as amino, sulfur or one-carbon group donors. There is a high natural variation in vitamin contents in crops and its exploitation through breeding, metabolic engineering and agronomic practices can enhance their nutritional quality. While the underlying biochemical roles of vitamins as cosubstrates or cofactors are usually common for most eukaryotes, the impact of vitamins B and E in metabolism and physiology can be quite different on plants and animals. Here, we first aim at giving an overview of the biosynthesis of amino acid-derived vitamins in plants, with a particular focus on how this knowledge can be exploited to increase vitamin contents in crops. Second, we will focus on the functions of these vitamins in both plants and animals (and humans in particular), to unravel common and specific roles for vitamins in evolutionary distant organisms, in which these amino acid-derived vitamins play, however, an essential role.

  13. Biarylalkyl Carboxylic Acid Derivatives as Novel Antischistosomal Agents.

    PubMed

    Mäder, Patrick; Blohm, Ariane S; Quack, Thomas; Lange-Grünweller, Kerstin; Grünweller, Arnold; Hartmann, Roland K; Grevelding, Christoph G; Schlitzer, Martin

    2016-07-01

    Parasitic platyhelminths are responsible for serious infectious diseases, such as schistosomiasis, which affect humans as well as animals across vast regions of the world. The drug arsenal available for the treatment of these diseases is limited; for example, praziquantel is the only drug currently used to treat ≥240 million people each year infected with Schistosoma spp., and there is justified concern about the emergence of drug resistance. In this study, we screened biarylalkyl carboxylic acid derivatives for their antischistosomal activity against S. mansoni. These compounds showed significant influence on egg production, pairing stability, and vitality. Tegumental lesions or gut dilatation was also observed. Substitution of the terminal phenyl residue in the biaryl scaffold with a 3-hydroxy moiety and derivatization of the terminal carboxylic acid scaffold with carboxamides yielded compounds that displayed significant antischistosomal activity at concentrations as low as 10 μm with satisfying cytotoxicity values. The present study provides detailed insight into the structure-activity relationships of biarylalkyl carboxylic acid derivatives and thereby paves the way for a new drug-hit moiety for fighting schistosomiasis. PMID:27159334

  14. Antiherbivore prenylated benzoic acid derivatives from Piper kelleyi.

    PubMed

    Jeffrey, Christopher S; Leonard, Michael D; Glassmire, Andrea E; Dodson, Craig D; Richards, Lora A; Kato, Massuo J; Dyer, Lee A

    2014-01-24

    The known prenylated benzoic acid derivative 3-geranyl-4-hydroxy-5-(3″,3″-dimethylallyl)benzoic acid (1) and two new chromane natural products were isolated from the methanolic extract of the leaves of Piper kelleyi Tepe (Piperaceae), a midcanopy tropical shrub that grows in lower montane rain forests in Ecuador and Peru. Structure determination using 1D and 2D NMR analysis led to the structure of the chromene 2 and to the reassignment of the structure of cumanensic acid as 4, an isomeric chromene previously isolated from Piper gaudichaudianum. The structure and relative configuration of new chromane 3 was determined using 1D and 2D NMR spectroscopic analysis and was found to be racemic by ECD spectropolarimetry. The biological activity of 1-3 was evaluated against a lab colony of the generalist caterpillar Spodoptera exigua (Noctuidae), and low concentrations of 2 and 3 were found to significantly reduce fitness. Further consideration of the biosynthetic relationship of the three compounds led to the proposal that 1 is converted to 2 via an oxidative process, whereas 3 is produced through hetero-[4+2] dimerization of a quinone methide derived from the chromene 2.

  15. Antiherbivore prenylated benzoic acid derivatives from Piper kelleyi.

    PubMed

    Jeffrey, Christopher S; Leonard, Michael D; Glassmire, Andrea E; Dodson, Craig D; Richards, Lora A; Kato, Massuo J; Dyer, Lee A

    2014-01-24

    The known prenylated benzoic acid derivative 3-geranyl-4-hydroxy-5-(3″,3″-dimethylallyl)benzoic acid (1) and two new chromane natural products were isolated from the methanolic extract of the leaves of Piper kelleyi Tepe (Piperaceae), a midcanopy tropical shrub that grows in lower montane rain forests in Ecuador and Peru. Structure determination using 1D and 2D NMR analysis led to the structure of the chromene 2 and to the reassignment of the structure of cumanensic acid as 4, an isomeric chromene previously isolated from Piper gaudichaudianum. The structure and relative configuration of new chromane 3 was determined using 1D and 2D NMR spectroscopic analysis and was found to be racemic by ECD spectropolarimetry. The biological activity of 1-3 was evaluated against a lab colony of the generalist caterpillar Spodoptera exigua (Noctuidae), and low concentrations of 2 and 3 were found to significantly reduce fitness. Further consideration of the biosynthetic relationship of the three compounds led to the proposal that 1 is converted to 2 via an oxidative process, whereas 3 is produced through hetero-[4+2] dimerization of a quinone methide derived from the chromene 2. PMID:24422717

  16. Lactic acid production from lignocellulose-derived sugars using lactic acid bacteria: overview and limits.

    PubMed

    Abdel-Rahman, Mohamed Ali; Tashiro, Yukihiro; Sonomoto, Kenji

    2011-12-20

    Lactic acid is an industrially important product with a large and rapidly expanding market due to its attractive and valuable multi-function properties. The economics of lactic acid production by fermentation is dependent on many factors, of which the cost of the raw materials is very significant. It is very expensive when sugars, e.g., glucose, sucrose, starch, etc., are used as the feedstock for lactic acid production. Therefore, lignocellulosic biomass is a promising feedstock for lactic acid production considering its great availability, sustainability, and low cost compared to refined sugars. Despite these advantages, the commercial use of lignocellulose for lactic acid production is still problematic. This review describes the "conventional" processes for producing lactic acid from lignocellulosic materials with lactic acid bacteria. These processes include: pretreatment of the biomass, enzyme hydrolysis to obtain fermentable sugars, fermentation technologies, and separation and purification of lactic acid. In addition, the difficulties associated with using this biomass for lactic acid production are especially introduced and several key properties that should be targeted for low-cost and advanced fermentation processes are pointed out. We also discuss the metabolism of lignocellulose-derived sugars by lactic acid bacteria.

  17. Experimental and theoretical study on benzoic acid derivatives

    NASA Astrophysics Data System (ADS)

    Świsłocka, R.; Regulska, E.; Samsonowicz, M.; Lewandowski, W.

    2013-07-01

    Benzoic (BA), p-hydroxybenzoic (HBA), m-methoxybenzoic (MBA), vanillic (VA) and syringic (SGA) acids were studied using both experimental and theoretical tools. The vibrational (FT-IR, FT-Raman) and 1H and 13C NMR spectra of benzoic acid derivatives were recorded. Characteristic shifts and changes in intensities of bands along the studied series were observed. The changes of chemical shifts of protons (1H NMR) and carbons (13C NMR) in the series of studied compounds were observed too. Optimized geometrical structures of studied compounds were obtained by B3LYP method using 6-31++G**, 6-311+G** and 6-311++G** basis sets. Aromaticity indices, atomic charges, dipole moments and energies were calculated. The theoretical chemical shifts in 1H and 13C NMR spectra and theoretical wavenumbers and intensities of IR and Raman spectra were determined. The calculated parameters were compared to experimental characteristic of studied compounds.

  18. Novel sustainable polymers derived from renewable rosin and fatty acids

    NASA Astrophysics Data System (ADS)

    Wilbon, Perry

    In the work of this dissertation, polymers derived from renewable bio-based resources prepared by various polymerization techniques were investigated. The properties of these polymeric materials were characterized and discussed. Rosin was first converted into acrylate or methacrylate monomers for atom transfer radical polymerization (ATRP). Second, rosin was combined with vegetable oil to produce completely renewable novel polyesters by acyclic diene metathesis (ADMET) polymerization. Third, degradable block copolymers were synthesized composed of polycaprolactone and rosin grafted polycaprolactone with the aid of ring-opening polymerization (ROP). Finally, degradable polyesters were produced using vegetable oil derivatives as starting materials. These new rosin and fatty acid based renewable polymer materials will have potential applications as sustainable thermoplastics, thermoplastic elastomers, etc.

  19. Synthesis and biological activity of novel deoxycholic acid derivatives.

    PubMed

    Popadyuk, Irina I; Markov, Andrey V; Salomatina, Oksana V; Logashenko, Evgeniya B; Shernyukov, Andrey V; Zenkova, Marina A; Salakhutdinov, Nariman F

    2015-08-01

    We report the synthesis and biological activity of new semi-synthetic derivatives of naturally occurring deoxycholic acid (DCA) bearing 2-cyano-3-oxo-1-ene, 3-oxo-1(2)-ene or 3-oxo-4(5)-ene moieties in ring A and 12-oxo or 12-oxo-9(11)-ene moieties in ring C. Bioassays using murine macrophage-like cells and tumour cells show that the presence of the 9(11)-double bond associated with the increased polarity of ring A or with isoxazole ring joined to ring A, improves the ability of the compounds to inhibit cancer cell growth. PMID:26037611

  20. Synthesis and biological activity of novel deoxycholic acid derivatives.

    PubMed

    Popadyuk, Irina I; Markov, Andrey V; Salomatina, Oksana V; Logashenko, Evgeniya B; Shernyukov, Andrey V; Zenkova, Marina A; Salakhutdinov, Nariman F

    2015-08-01

    We report the synthesis and biological activity of new semi-synthetic derivatives of naturally occurring deoxycholic acid (DCA) bearing 2-cyano-3-oxo-1-ene, 3-oxo-1(2)-ene or 3-oxo-4(5)-ene moieties in ring A and 12-oxo or 12-oxo-9(11)-ene moieties in ring C. Bioassays using murine macrophage-like cells and tumour cells show that the presence of the 9(11)-double bond associated with the increased polarity of ring A or with isoxazole ring joined to ring A, improves the ability of the compounds to inhibit cancer cell growth.

  1. Gallic acid-based indanone derivatives as anticancer agents.

    PubMed

    Saxena, Hari Om; Faridi, Uzma; Srivastava, Suchita; Kumar, J K; Darokar, M P; Luqman, Suaib; Chanotiya, C S; Krishna, Vinay; Negi, Arvind S; Khanuja, S P S

    2008-07-15

    Gallic acid-based indanone derivatives have been synthesised. Some of the indanones showed very good anticancer activity in MTT assay. Compounds 10, 11, 12 and 14 possessed potent anticancer activity against various human cancer cell lines. The most potent indanone (10, IC(50)=2.2 microM), against MCF-7, that is, hormone-dependent breast cancer cell line, showed no toxicity to human erythrocytes even at higher concentrations (100 microg/ml, 258 microM). While, indanones 11, 12 and 14 showed toxicities to erythrocytes at higher concentrations.

  2. Esterification of fermentation-derived acids via pervaporation

    DOEpatents

    Datta, R.; Tsai, S.P.

    1998-03-03

    A low temperature method for esterifying ammonium- and amine-containing salts is provided whereby the salt is reacted with an alcohol in the presence of heat and a catalyst and then subjected to a dehydration and deamination process using pervaporation. The invention also provides for a method for producing esters of fermentation derived, organic acid salt comprising first cleaving the salt into its cationic part and anionic part, mixing the anionic part with an alcohol to create a mixture; heating the mixture in the presence of a catalyst to create an ester; dehydrating the now heated mixture; and separating the ester from the now-dehydrated mixture. 2 figs.

  3. Esterification of fermentation-derived acids via pervaporation

    DOEpatents

    Datta, Rathin; Tsai, Shih-Perng

    1998-01-01

    A low temperature method for esterifying ammonium- and amine-containing salts is provided whereby the salt is reacted with an alcohol in the presence of heat and a catalyst and then subjected to a dehydration and deamination process using pervaporation. The invention also provides for a method for producing esters of fermentation derived, organic acid salt comprising first cleaving the salt into its cationic part and anionic part, mixing the anionic part with an alcohol to create a mixture; heating the mixture in the presence of a catalyst to create an ester; dehydrating the now heated mixture; and separating the ester from the now-dehydrated mixture.

  4. Injectable hydrogels derived from phosphorylated alginic acid calcium complexes.

    PubMed

    Kim, Han-Sem; Song, Minsoo; Lee, Eun-Jung; Shin, Ueon Sang

    2015-06-01

    Phosphorylation of sodium alginate salt (NaAlg) was carried out using H3PO4/P2O5/Et3PO4 followed by acid-base reaction with Ca(OAc)2 to give phosphorylated alginic acid calcium complexes (CaPAlg), as a water dispersible alginic acid derivative. The modified alginate derivatives including phosphorylated alginic acid (PAlg) and CaPAlg were characterized by nuclear magnetic resonance spectroscopy for (1)H, and (31)P nuclei, high resolution inductively coupled plasma optical emission spectroscopy, Fourier transform infrared spectroscopy, and thermogravimetric analysis. CaPAlg hydrogels were prepared simply by mixing CaPAlg solution (2w/v%) with NaAlg solution (2w/v%) in various ratios (2:8, 4:6, 6:4, 8:2) of volume. No additional calcium salts such as CaSO4 or CaCl2 were added externally. The gelation was completed within about 3-40min indicating a high potential of hydrogel delivery by injection in vivo. Their mechanical properties were tested to be ≤6.7kPa for compressive strength at break and about 8.4kPa/mm for elastic modulus. SEM analysis of the CaPAlg hydrogels showed highly porous morphology with interconnected pores of width in the range of 100-800μm. Cell culture results showed that the injectable hydrogels exhibited comparable properties to the pure alginate hydrogel in terms of cytotoxicity and 3D encapsulation of cells for a short time period. The developed injectable hydrogels showed suitable physicochemical and mechanical properties for injection in vivo, and could therefore be beneficial for the field of soft tissue engineering. PMID:25842118

  5. Interactions of amino acids, carboxylic acids, and mineral acids with different quinoline derivatives

    NASA Astrophysics Data System (ADS)

    Kalita, Dipjyoti; Deka, Himangshu; Samanta, Shyam Sundar; Guchait, Subrata; Baruah, Jubaraj B.

    2011-03-01

    A series of quinoline containing receptors having amide and ester bonds are synthesized and characterised. The relative binding abilities of these receptors with various amino acids, carboxylic acids and mineral acids are determined by monitoring the changes in fluorescence intensity. Among the receptors bis(2-(quinolin-8-yloxy)ethyl) isophthalate shows fluorescence enhancement on addition of amino acids whereas the other receptors shows fluorescence quenching on addition of amino acids. The receptor N-(quinolin-8-yl)-2-(quinolin-8-yloxy) propanamide has higher binding affinity for amino acids. However, the receptor N-(quinolin-8-yl)-2-(quinolin-8-yloxy)acetamide having similar structure do not bind to amino acids. This is attributed to the concave structure of the former which is favoured due to the presence of methyl substituent. The receptor bis(2-(quinolin-8-yloxy)ethyl) isophthalate do not bind to hydroxy carboxylic acids, but is a good receptor for dicarboxylic acids. The crystal structure of bromide and perchlorate salts of receptor 2-bromo-N-(quinolin-8-yl)-propanamide are determined. In both the cases the amide groups are not in the plane of quinoline ring. The structure of N-(quinolin-8-yl)-2-(quinolin-8-yloxy)acetamide, N-(2-methoxyphenethyl)-2-(quinolin-8-yloxy)acetamide and their salts with maleic acid as well as fumaric acid are determined. It is observed that the solid state structures are governed by the double bond geometry of these two acid. Maleic acid forms salt in both the cases, whereas fumaric acid forms either salt or co-crystals.

  6. 40 CFR 721.6110 - Alkyldi(alkyloxyhydroxypropyl) derivative, phosphoric acid esters, potassium salts.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...) derivative, phosphoric acid esters, potassium salts. 721.6110 Section 721.6110 Protection of Environment...) derivative, phosphoric acid esters, potassium salts. (a) Chemical substance and significant new uses subject...) derivative, phosphoric acid esters, potassium salts (PMN P-91-818) is subject to reporting under this...

  7. 40 CFR 721.6110 - Alkyldi(alkyloxyhydroxypropyl) derivative, phosphoric acid esters, potassium salts.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...) derivative, phosphoric acid esters, potassium salts. 721.6110 Section 721.6110 Protection of Environment...) derivative, phosphoric acid esters, potassium salts. (a) Chemical substance and significant new uses subject...) derivative, phosphoric acid esters, potassium salts (PMN P-91-818) is subject to reporting under this...

  8. Alkyl hydroxybenzoic acid derivatives that inhibit HIV-1 protease dimerization.

    PubMed

    Flausino, O A; Dufau, L; Regasini, L O; Petrônio, M S; Silva, D H S; Rose, T; Bolzani, V S; Reboud-Ravaux, M

    2012-01-01

    The therapeutic potential of gallic acid and its derivatives as anti-cancer, antimicrobial and antiviral agents is well known. We have examined the mechanism by which natural gallic acid and newly synthesized gallic acid alkyl esters and related protocatechuic acid alkyl esters inhibit HIV-1 protease to compare the influence of the aromatic ring substitutions on inhibition. We used Zhang-Poorman's kinetic analysis and fluorescent probe binding to demonstrate that several gallic and protecatechuic acid alkyl esters inhibited HIV-1 protease by preventing the dimerization of this obligate homodimeric aspartic protease rather than targeting the active site. The tri-hydroxy substituted benzoic moiety in gallates was more favorable than the di-substituted one in protocatechuates. In both series, the type of inhibition, its mechanism and the inhibitory efficiency dramatically depended on the length of the alkyl chain: no inhibition with alkyl chains less than 8 carbon atoms long. Molecular dynamics simulations corroborated the kinetic data and propose that gallic esters are intercalated between the two N- and C-monomer ends. They complete the β-sheet and disrupt the dimeric enzyme. The best gallic ester (14 carbon atoms, K(id) of 320 nM) also inhibited the multi-mutated protease MDR-HM. These results will aid the rational design of future generations of non-peptide inhibitors of HIV-1 protease dimerization that inhibit multi-mutated proteases. Finally, our work suggests the wide use of gallic and protocatechuic alkyl esters to dissociate intermolecular β-sheets involved in protein-protein interactions.

  9. Infrared Spectroscopy of Hydrogen Bonds in Benzoic Acid Derivatives

    NASA Astrophysics Data System (ADS)

    Tolstorozhev, G. B.; Bel‧kov, M. V.; Skornyakov, I. V.; Bazyl, O. K.; Artyukhov, V. Ya.; Mayer, G. V.; Shadyro, O. I.; Kuzovkov, P. V.; Brinkevich, S. D.; Samovich, S. N.

    2014-03-01

    We have measured the Fourier transform IR spectra of CCl4 solutions of benzoic acid and its biologically active derivatives. We investigated the proton-acceptor properties of the studied molecules theoretically by the molecular electrostatic potential method. The calculations are compared with experimental results. Based on an estimate of the proton-acceptor properties, we give an interpretation of the specific features of the IR spectra of benzoic acid and its derivatives in the region of the O-H and C = O vibrations. The mechanisms for interactions of the molecules are determined by the nature of substituents which are added to the benzene ring in positions para and meta to the carboxyl group. We identify the conditions for appearance of intermolecular hydrogen bonds of O-H · · · O = C, O-H · · · O-H types with formation of cyclic and linear dimers. We show that intramolecular hydrogen bonds of the type O-H · · · O-CH3 prevent the hydroxyl groups from participating in intermolecular interactions.

  10. Synthesis and antimicrobial activities of new higher amino acid Schiff base derivatives of 6-aminopenicillanic acid and 7-aminocephalosporanic acid

    NASA Astrophysics Data System (ADS)

    Özdemir (nee Güngör), Özlem; Gürkan, Perihan; Özçelik, Berrin; Oyardı, Özlem

    2016-02-01

    Novel β-lactam derivatives (1c-3c) (1d-3d) were produced by using 6-aminopenicillanic acid (6-APA), 7-aminocephalosporanic acid (7-ACA) and the higher amino acid Schiff bases. The synthesized compounds were characterized by elemental analysis, IR, 1H/13C NMR and UV-vis spectra. Antibacterial activities of all the higher amino acid Schiff bases (1a-3a) (1b-3b) and β-lactam derivatives were screened against three gram negative bacteria (Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Acinetobacter baumannii RSKK 02026), three gram positive bacteria (Staphylococcus aureus ATCC 25923, Enterococcus faecalis ATCC 07005, Bacillus subtilis ATCC 6633) and their drug-resistant isolates by using broth microdilution method. Two fungi (Candida albicans and Candida krusei) were used for antifungal activity.

  11. Hydroxamic acid derivatives of mycophenolic acid inhibit histone deacetylase at the cellular level.

    PubMed

    Batovska, Daniela I; Kim, Dong Hoon; Mitsuhashi, Shinya; Cho, Yoon Sun; Kwon, Ho Jeong; Ubukata, Makoto

    2008-10-01

    Mycophenolic acid (MPA, 1), an inhibitor of IMP-dehydrogenase (IMPDH) and a latent PPARgamma agonist, is used as an effective immunosuppressant for clinical transplantation and recently entered clinical trials in advanced multiple myeloma patients. On the other hand, suberoylanilide hydroxamic acid (SAHA), a non-specific histone deacetylase (HDAC) inhibitor, has been approved for treating cutaneous T-cell lymphoma. MPA seemed to bear a cap, a linker, and a weak metal-binding site as a latent inhibitor of HDAC. Therefore, the hydroxamic acid derivatives of mycophenolic acid having an effective metal-binding site, mycophenolic hydroxamic acid (MPHA, 2), 7-O-acetyl mycophenolic acid (7-O-Ac MPHA, 3), and 7-O-lauroyl mycophenolic hydroxamic acid (7-O-L MPHA, 4) were designed and synthesized. All these compounds inhibited histone deacetylase with IC50 values of 1, 0.9 and 0.5 microM, and cell proliferation at concentrations of 2, 1.5 and 1 microM, respectively. PMID:18838793

  12. Teratogenicity of benzoic acid derivatives of retinoic acid in cultured mouse embryos.

    PubMed

    Goulding, E H; Jetten, A M; Abbott, B D; Pratt, R M

    1988-01-01

    Isotretinoin (13-cis-RA) is a human teratogen and mouse embryos exposed to 13-cis-RA in vivo exhibit many of the same defects as humans. Early postimplantation mouse embryos exposed to 13-cis-RA in culture exhibit developmental alterations of the visceral arches, similar to those seen after in vivo exposure. Certain benzoic acid derivatives of retinoic acid have been shown to possess activity equal to or greater than retinoic acid in several in vitro systems. This study examines the teratogenic effects of some of these retinoids on mouse embryos in vitro. Day 8 CD-1 mouse embryos were cultured for 48 hours in the presence of these benzoic acid derivatives. With the exception of Ro-15-0778, all compounds produced visceral arch malformations similar to those seen in embryos exposed to 13-cis-RA, but at dramatically different effective concentrations. Extremely low concentrations of the retinoic acid-related compounds tested appear to have detrimental effects on embryonic development and these compounds may be poor candidates for therapeutic use.

  13. A potential plant-derived antifungal acetylenic acid mediates its activity by interfering with fatty acid homeostasis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    6-Nonadecynoic acid (6-NDA), a plant-derived acetylenic acid, exhibits strong inhibitory activity against the human fungal pathogens Candida albicans, Aspergillus fumigatus, and Trichophyton mentagrophytes. In the present study, transcriptional profiling coupled with mutant and biochemical analyses...

  14. Microbial production of hyaluronic acid from agricultural resource derivatives.

    PubMed

    Pires, Aline M B; Macedo, André C; Eguchi, Silvia Y; Santana, Maria H A

    2010-08-01

    Agricultural resource derivatives (ARDs) such as hydrolysate soy protein concentrate (HSPC), whey protein concentrate (WPC), and cashew apple juice (CAJ) were studied with focus on the production of hyaluronic acid (HA) by Streptococcus zooepidemicus. Supplementation of the media with corn steep liquor (CSL) was also evaluated. Synthetic medium containing glucose and yeast extract was used as control. CAJ was a promising medium for the production of HA. It produced the highest amount of HA (0.89 g L(-1)), similar to that of the control (0.86 g L(-1)). WPC and HSPC media were the most effective for the production of biomass. CSL did not influence the production of HA when HSPC and WPC were used. However, in the synthetic medium it doubled the yield of HA from glucose. The average molecular weight of HA ranged from 10(3) to 10(4)Da for the ARDs and 10(7)Da for the synthetic medium.

  15. Frustrated smectic liquid crystalline phases in lactic acid derivatives

    NASA Astrophysics Data System (ADS)

    Glogarová, M.; Novotná, V.

    2016-08-01

    We have prepared and studied a series of compounds with different types of molecular core and lactate unit in the chiral terminal chain. We draw a survey and comparison of their mesomorphic properties with respect to the occurrence of twist grain boundary (TGB) phases. The materials exhibit extremely wide TGBA phase more than 60K broad, unique TGBA-TGBC-SmC*-SmCA* phase sequence and unique re-entrant TGBA phase below the SmA phase. TGB phases have been induced in binary mixtures of molecules with different molecular shape and chirality (chiral lactic acid derivative and non-chiral hockey-stick mesogen). Unique effect is observed for compounds with TGBA phase, where the applied electric field transforms the planar texture into the homeotropic one, homogeneously dark in crossed polarizers. The process is analogy of the Frederiks transition so far known only for nematics. This effect, changing the bright state to the dark one, is promising for applications.

  16. Four New Dicaffeoylquinic Acid Derivatives from Glasswort (Salicornia herbacea L.) and Their Antioxidative Activity.

    PubMed

    Cho, Jeong-Yong; Kim, Jin Young; Lee, Yu Geon; Lee, Hyoung Jae; Shim, Hyun Jeong; Lee, Ji Hye; Kim, Seon-Jae; Ham, Kyung-Sik; Moon, Jae-Hak

    2016-01-01

    Four new dicaffeoylquinic acid derivatives and two known 3-caffeoylquinic acid derivatives were isolated from methanol extracts using the aerial parts of Salicornia herbacea. The four new dicaffeoylquinic acid derivatives were established as 3-caffeoyl-5-dihydrocaffeoylquinic acid, 3-caffeoyl-5-dihydrocaffeoylquinic acid methyl ester, 3-caffeoyl-4-dihydrocaffeoylquinic acid methyl ester, and 3,5-di-dihydrocaffeoylquinic acid methyl ester. Their chemical structures were determined by nuclear magnetic resonance and electrospray ionization-mass spectroscopy (LC-ESI-MS). In addition, the presence of dicaffeoylquinic acid derivatives in this plant was reconfirmed by LC-ESI-MS/MS analysis. The isolated compounds strongly scavenged 1,1-diphenyl-2-picrylhydrazyl radicals and inhibited cholesteryl ester hydroperoxide formation during rat blood plasma oxidation induced by copper ions. These results indicate that the caffeoylquinic acid derivatives may partially contribute to the antioxidative effect of S. herbacea. PMID:27556430

  17. Four New Dicaffeoylquinic Acid Derivatives from Glasswort (Salicornia herbacea L.) and Their Antioxidative Activity.

    PubMed

    Cho, Jeong-Yong; Kim, Jin Young; Lee, Yu Geon; Lee, Hyoung Jae; Shim, Hyun Jeong; Lee, Ji Hye; Kim, Seon-Jae; Ham, Kyung-Sik; Moon, Jae-Hak

    2016-08-20

    Four new dicaffeoylquinic acid derivatives and two known 3-caffeoylquinic acid derivatives were isolated from methanol extracts using the aerial parts of Salicornia herbacea. The four new dicaffeoylquinic acid derivatives were established as 3-caffeoyl-5-dihydrocaffeoylquinic acid, 3-caffeoyl-5-dihydrocaffeoylquinic acid methyl ester, 3-caffeoyl-4-dihydrocaffeoylquinic acid methyl ester, and 3,5-di-dihydrocaffeoylquinic acid methyl ester. Their chemical structures were determined by nuclear magnetic resonance and electrospray ionization-mass spectroscopy (LC-ESI-MS). In addition, the presence of dicaffeoylquinic acid derivatives in this plant was reconfirmed by LC-ESI-MS/MS analysis. The isolated compounds strongly scavenged 1,1-diphenyl-2-picrylhydrazyl radicals and inhibited cholesteryl ester hydroperoxide formation during rat blood plasma oxidation induced by copper ions. These results indicate that the caffeoylquinic acid derivatives may partially contribute to the antioxidative effect of S. herbacea.

  18. A new helvolic acid derivative from an endophytic Fusarium sp. of Ficus carica.

    PubMed

    Liang, Xi-Ai; Ma, Yang-Min; Zhang, Hong-Chi; Liu, Rui

    2016-11-01

    A new helvolic acid derivative named helvolic acid methyl ester (1), together with two known helvolic acid compounds, helvolic acid (2) and hydrohelvolic acid (3), were isolated from the fermentation of endophytic fungus Fusarium sp. in Ficus carica leaves. Their structures were elucidated and identified by spectroscopic methods. Compounds 1-3 showed potent antifungal and antibacterial activities. PMID:27265219

  19. Gallic acid and gallic acid derivatives: effects on drug metabolizing enzymes.

    PubMed

    Ow, Yin-Yin; Stupans, Ieva

    2003-06-01

    Gallic acid and its structurally related compounds are found widely distributed in fruits and plants. Gallic acid, and its catechin derivatives are also present as one of the main phenolic components of both black and green tea. Esters of gallic acid have a diverse range of industrial uses, as antioxidants in food, in cosmetics and in the pharmaceutical industry. In addition, gallic acid is employed as a source material for inks, paints and colour developers. Studies utilising these compounds have found them to possess many potential therapeutic properties including anti-cancer and antimicrobial properties. In this review, studies of the effects of gallic acid, its esters, and gallic acid catechin derivatives on Phase I and Phase II enzymes are examined. Many published reports of the effects of the in vitro effects of gallic acid and its derivatives on drug metabolising enzymes concern effects directly on substrate (generally drug or mutagen) metabolism or indirectly through observed effects in Ames tests. In the case of the Ames test an antimutagenic effect may be observed through inhibition of CYP activation of indirectly acting mutagens and/or by scavenging of metabolically generated mutagenic electrophiles. There has been considerable interest in the in vivo effects of the gallate esters because of their incorporation into foodstuffs as antioxidants and in the catechin gallates with their potential role as chemoprotective agents. Principally an induction of Phase II enzymes has been observed however more recent studies using HepG2 cells and primary cultures of human hepatocytes provide evidence for the overall complexity of actions of individual components versus complex mixtures, such as those in food. Further systematic studies of mechanisms of induction and inhibition of drug metabolising enzymes by this group of compounds are warranted in the light of their distribution and consequent ingestion, current uses and suggested therapeutic potential. However, it

  20. 40 CFR 721.430 - Oxo-substituted amino-al-kanoic acid derivative.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Oxo-substituted amino-al-kanoic acid... Specific Chemical Substances § 721.430 Oxo-substituted amino-al-kanoic acid derivative. (a) Chemical... as oxo-substituted amino al-kan-oic acid derivative (PMN No. P-92-692) is subject to reporting...

  1. 40 CFR 721.430 - Oxo-substituted amino-al-kanoic acid derivative.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Oxo-substituted amino-al-kanoic acid... Specific Chemical Substances § 721.430 Oxo-substituted amino-al-kanoic acid derivative. (a) Chemical... as oxo-substituted amino al-kan-oic acid derivative (PMN No. P-92-692) is subject to reporting...

  2. 40 CFR 721.430 - Oxo-substituted amino-al-kanoic acid derivative.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Oxo-substituted amino-al-kanoic acid... Specific Chemical Substances § 721.430 Oxo-substituted amino-al-kanoic acid derivative. (a) Chemical... as oxo-substituted amino al-kan-oic acid derivative (PMN No. P-92-692) is subject to reporting...

  3. 40 CFR 721.430 - Oxo-substituted amino-al-kanoic acid derivative.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Oxo-substituted amino-al-kanoic acid... Specific Chemical Substances § 721.430 Oxo-substituted amino-al-kanoic acid derivative. (a) Chemical... as oxo-substituted amino al-kan-oic acid derivative (PMN No. P-92-692) is subject to reporting...

  4. 40 CFR 721.430 - Oxo-substituted amino-al-kanoic acid derivative.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Oxo-substituted amino-al-kanoic acid... Specific Chemical Substances § 721.430 Oxo-substituted amino-al-kanoic acid derivative. (a) Chemical... as oxo-substituted amino al-kan-oic acid derivative (PMN No. P-92-692) is subject to reporting...

  5. 40 CFR 721.10045 - Diazotized substituted heteromonocycle coupled with naphthalene sulfonic acid derivative, nickel...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... coupled with naphthalene sulfonic acid derivative, nickel complex, alkaline salt (generic). 721.10045... derivative, nickel complex, alkaline salt (generic). (a) Chemical substance and significant new uses subject... heteromonocycle coupled with naphthalene sulfonic acid derivative, nickel complex, alkaline salt (PMN P-02-737)...

  6. 40 CFR 721.10045 - Diazotized substituted heteromonocycle coupled with naphthalene sulfonic acid derivative, nickel...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... coupled with naphthalene sulfonic acid derivative, nickel complex, alkaline salt (generic). 721.10045... derivative, nickel complex, alkaline salt (generic). (a) Chemical substance and significant new uses subject... heteromonocycle coupled with naphthalene sulfonic acid derivative, nickel complex, alkaline salt (PMN P-02-737)...

  7. 40 CFR 721.10045 - Diazotized substituted heteromonocycle coupled with naphthalene sulfonic acid derivative, nickel...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... coupled with naphthalene sulfonic acid derivative, nickel complex, alkaline salt (generic). 721.10045... derivative, nickel complex, alkaline salt (generic). (a) Chemical substance and significant new uses subject... heteromonocycle coupled with naphthalene sulfonic acid derivative, nickel complex, alkaline salt (PMN P-02-737)...

  8. 40 CFR 721.10045 - Diazotized substituted heteromonocycle coupled with naphthalene sulfonic acid derivative, nickel...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... coupled with naphthalene sulfonic acid derivative, nickel complex, alkaline salt (generic). 721.10045... derivative, nickel complex, alkaline salt (generic). (a) Chemical substance and significant new uses subject... heteromonocycle coupled with naphthalene sulfonic acid derivative, nickel complex, alkaline salt (PMN P-02-737)...

  9. 40 CFR 721.10045 - Diazotized substituted heteromonocycle coupled with naphthalene sulfonic acid derivative, nickel...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... coupled with naphthalene sulfonic acid derivative, nickel complex, alkaline salt (generic). 721.10045... derivative, nickel complex, alkaline salt (generic). (a) Chemical substance and significant new uses subject... heteromonocycle coupled with naphthalene sulfonic acid derivative, nickel complex, alkaline salt (PMN P-02-737)...

  10. Tetramic acid derivatives and polyphenols from sponge-derived fungus and their biological evaluation.

    PubMed

    Wang, Jun-Feng; Qin, Xiaochu; Xu, Fu-Quan; Zhang, Tianyu; Liao, Shengrong; Lin, Xiuping; Yang, Bin; Liu, Juan; Wang, Lishu; Tu, Zhengchao; Liu, Yonghong

    2015-01-01

    Fifteen compounds, including two tetramic acid derivatives, penicillenol A1 (1) and penicillenol A2 (2), six polyphenols containing both phenolic bisabolane sesquiterpenoid and diphenyl ether units, expansols A-F (3-8), together with six phenolic bisabolane sesquiterpenoids (9-14) and diorcinol (15), were isolated from the fermentation broth of the marine-derived fungus ZSDS1-F11 isolated from the sponge Phakellia fusca Thiele collected in the Yongxing island of Xisha. Their structures were elucidated mainly by using extensive NMR spectroscopic and mass spectrometric analyses. Compounds 3-5, 7 and 8 showed potent COX-1 inhibitory activity with IC50 values of 5.3, 16.2, 30.2, 41.0 and 56.8 μM, respectively. Meanwhile, compounds 3-8 showed potent COX-2 inhibitory activity with IC50 values of 3.1, 5.6, 3.0, 5.1, 3.2 and 3.7 μM, respectively. In addition, compound 1 exhibited antituberculosis activity with 96.1% inhibition at concentration of 10 μM.

  11. Energy densification of biomass-derived organic acids

    DOEpatents

    Wheeler, M. Clayton; van Walsum, G. Peter; Schwartz, Thomas J.; van Heiningen, Adriaan

    2013-01-29

    A process for upgrading an organic acid includes neutralizing the organic acid to form a salt and thermally decomposing the resulting salt to form an energy densified product. In certain embodiments, the organic acid is levulinic acid. The process may further include upgrading the energy densified product by conversion to alcohol and subsequent dehydration.

  12. Discotic liquid crystal derived from zinc tetraaminophthalocyanine and perfluorooctanoic acid

    NASA Astrophysics Data System (ADS)

    Meng, Fanbao; Zhou, Naiyu; Diao, Na; Du, Chang

    2013-12-01

    A novel kind of metallo-phthalocyanine derivative, zinc 2,9,16,23-tetraaminophthalocyanine perfluorooctanoate (Zn-APc-pFOA), was synthesized from zinc tetraaminophthalocyanine and perfluorooctanoic acid. The chemical structure, liquid crystalline behavior, and electrorheological properties were characterized by the use of various experimental techniques, methods, and instruments, including FT-IR and UV-vis spectroscopy, 1H-NMR, x-ray diffraction, differential scanning calorimetry, thermogravimetric analysis, polarized optical microscopy, the four-point method, a relative permittivity test instrument, and a rotating viscometer. Zn-APc-pFOA shows a discotic hexagonal columnar mesophase over a wide temperature range. The dielectric constant and conductivity of Zn-APc-pFOA are 11.4 and 6.34 × 10-3 S cm-1, respectively. The 20 V% silicone oil-Zn-APc-pFOA fluid shows an electrorheological (ER) effect. Zn-APc-pFOA is a semiconductor with a high dielectric constant, causing a mismatch of conductivity and dielectric constant between the Zn-APc-pFOA and silicone oil. Furthermore, some synergistic effect could occur between the semiconducting property and the molecular orientation of the discotic liquid crystals in Zn-APc-pFOA suspensions, resulting in a high ER effect.

  13. Inhibition of fucosyltransferase VII by gallic acid and its derivatives.

    PubMed

    Niu, Xiaoda; Fan, Xuedong; Sun, Jing; Ting, Pauline; Narula, Satwant; Lundell, Daniel

    2004-05-01

    Gallic acid (GA) and several gallate derivatives were identified as inhibitors of fucosyltransferase VII (FucT VII). The inhibition by GA and (-)-epigallocatechin gallate (EGCG) is time-dependent and irreversible. GA and EGCG showed inhibition with IC(50) of 60 and 700 nM, respectively, after pre-incubation with FucT VII in the presence of MnCl(2). Absence of MnCl(2) results in significantly weaker inhibition. Complexation of Mn(2+) with GA, EGCG, and gallate esters was observed. Such complexation, however, is not rate-limiting for the inhibition of FucT VII. Therefore, time-dependent inhibition of fucosyltransferases by GA and EGCG is likely due to the slow inactivation by the inhibitors or Mn-inhibitor complex. Although Mg(2+) or Ca(2+) can replace Mn(2+) for FucT VII activation, none forms a complex with GA or EGCG and hence results in weaker inhibition of FucT VII. GA and EGCG also inhibit FucT IV and alpha2,3-(N)-sialyltransferase in the low micromolar range. The structure-function divergence could be observed, as EGCG, but not GA or gallate esters, inhibits Zn(2+) containing metalloproteases such as TNFalpha convertase, matrix metalloproteases 2 and 7.

  14. Human liver apolipoprotein B-100 cDNA: complete nucleic acid and derived amino acid sequence.

    PubMed Central

    Law, S W; Grant, S M; Higuchi, K; Hospattankar, A; Lackner, K; Lee, N; Brewer, H B

    1986-01-01

    Human apolipoprotein B-100 (apoB-100), the ligand on low density lipoproteins that interacts with the low density lipoprotein receptor and initiates receptor-mediated endocytosis and low density lipoprotein catabolism, has been cloned, and the complete nucleic acid and derived amino acid sequences have been determined. ApoB-100 cDNAs were isolated from normal human liver cDNA libraries utilizing immunoscreening as well as filter hybridization with radiolabeled apoB-100 oligodeoxynucleotides. The apoB-100 mRNA is 14.1 kilobases long encoding a mature apoB-100 protein of 4536 amino acids with a calculated amino acid molecular weight of 512,723. ApoB-100 contains 20 potential glycosylation sites, and 12 of a total of 25 cysteine residues are located in the amino-terminal region of the apolipoprotein providing a potential globular structure of the amino terminus of the protein. ApoB-100 contains relatively few regions of amphipathic helices, but compared to other human apolipoproteins it is enriched in beta-structure. The delineation of the entire human apoB-100 sequence will now permit a detailed analysis of the conformation of the protein, the low density lipoprotein receptor binding domain(s), and the structural relationship between apoB-100 and apoB-48 and will provide the basis for the study of genetic defects in apoB-100 in patients with dyslipoproteinemias. PMID:3464946

  15. Benzoic acid derivatives from Piper species and their fungitoxic activity against Cladosporium cladosporioides and C. sphaerospermum.

    PubMed

    Lago, João Henrique G; Ramos, Clécio Sousa; Casanova, Diego Campos C; Morandim, Andreia de A; Bergamo, Debora Cristina B; Cavalheiro, Alberto J; Bolzani, Vanderlan da S; Furlan, Maysa; Guimarães, Elsie F; Young, Maria Claudia M; Kato, Massuo J

    2004-11-01

    Piper crassinervium, P. aduncum, P. hostmannianum, and P. gaudichaudianum contain the new benzoic acid derivatives crassinervic acid (1), aduncumene (8), hostmaniane (18), and gaudichaudianic acid (20), respectively, as major secondary metabolites. Additionally, 19 known compounds such as benzoic acids, chromenes, and flavonoids were isolated and identified. The antifungal activity of these compounds was evaluated by bioautographic TLC assay against Cladosporium cladosporioides and C. sphaerospermum.

  16. Novel enzymatic synthesis of 4-O-cinnamoyl quinic and shikimic acid derivatives.

    PubMed

    Armesto, Nuria; Ferrero, Miguel; Fernández, Susana; Gotor, Vicente

    2003-07-11

    The first direct synthesis of 4-O-cinnamoyl derivatives of quinic and shikimic acids were accomplished by regioselective esterification with Candida antarctica lipase A. For hydrocinnamic esters, enzymatic transesterification with vinyl esters gave excellent yields. However, more reactive acylating agents such as anhydrides were used to synthesize cinnamic derivatives of both acids. An inhibitory effect was observed with this lipase for p-methoxy, p-hydroxy, and p-acetoxy vinyl ester and anhydride derivatives (coumarate and ferulate derivatives).

  17. Pharmaceuticals and Surfactants from Alga-Derived Feedstock: Amidation of Fatty Acids and Their Derivatives with Amino Alcohols.

    PubMed

    Tkacheva, Anastasia; Dosmagambetova, Inkar; Chapellier, Yann; Mäki-Arvela, Päivi; Hachemi, Imane; Savela, Risto; Leino, Reko; Viegas, Carolina; Kumar, Narendra; Eränen, Kari; Hemming, Jarl; Smeds, Annika; Murzin, Dmitry Yu

    2015-08-24

    Amidation of renewable feedstocks, such as fatty acids, esters, and Chlorella alga based biodiesel, was demonstrated with zeolites and mesoporous materials as catalysts and ethanolamine, alaninol, and leucinol. The last two can be derived from amino acids present in alga. The main products were fatty alkanol amides and the corresponding ester amines, as confirmed by NMR and IR spectroscopy. Thermal amidation of technical-grade oleic acid and stearic acid at 180 °C with ethanolamine were non-negligible; both gave 61% conversion. In the amidation of stearic acid with ethanolamine, the conversion over H-Beta-150 was 80% after 3 h, whereas only 63% conversion was achieved for oleic acid; this shows that a microporous catalyst is not suitable for this acid and exhibits a wrinkled conformation. The highest selectivity to stearoyl ethanolamide of 92% was achieved with mildly acidic H-MCM-41 at 70% conversion in 3 h at 180 °C. Highly acidic catalysts favored the formation of the ester amine, whereas the amide was obtained with a catalyst that exhibited an optimum acidity. The conversion levels achieved with different fatty acids in the range C12-C18 were similar; this shows that the fatty acid length does not affect the amidation rate. The amidation of methyl palmitate and biodiesel gave low conversions over an acidic catalyst, which suggested that the reaction mechanism in the amidation of esters was different.

  18. Pharmaceuticals and Surfactants from Alga-Derived Feedstock: Amidation of Fatty Acids and Their Derivatives with Amino Alcohols.

    PubMed

    Tkacheva, Anastasia; Dosmagambetova, Inkar; Chapellier, Yann; Mäki-Arvela, Päivi; Hachemi, Imane; Savela, Risto; Leino, Reko; Viegas, Carolina; Kumar, Narendra; Eränen, Kari; Hemming, Jarl; Smeds, Annika; Murzin, Dmitry Yu

    2015-08-24

    Amidation of renewable feedstocks, such as fatty acids, esters, and Chlorella alga based biodiesel, was demonstrated with zeolites and mesoporous materials as catalysts and ethanolamine, alaninol, and leucinol. The last two can be derived from amino acids present in alga. The main products were fatty alkanol amides and the corresponding ester amines, as confirmed by NMR and IR spectroscopy. Thermal amidation of technical-grade oleic acid and stearic acid at 180 °C with ethanolamine were non-negligible; both gave 61% conversion. In the amidation of stearic acid with ethanolamine, the conversion over H-Beta-150 was 80% after 3 h, whereas only 63% conversion was achieved for oleic acid; this shows that a microporous catalyst is not suitable for this acid and exhibits a wrinkled conformation. The highest selectivity to stearoyl ethanolamide of 92% was achieved with mildly acidic H-MCM-41 at 70% conversion in 3 h at 180 °C. Highly acidic catalysts favored the formation of the ester amine, whereas the amide was obtained with a catalyst that exhibited an optimum acidity. The conversion levels achieved with different fatty acids in the range C12-C18 were similar; this shows that the fatty acid length does not affect the amidation rate. The amidation of methyl palmitate and biodiesel gave low conversions over an acidic catalyst, which suggested that the reaction mechanism in the amidation of esters was different. PMID:26197759

  19. THE DEVELOPMENTAL TOXICITY OF PERFLUOROALKYL ACIDS AND THEIR DERIVATIVES

    EPA Science Inventory

    Abstract

    Perfluoroalkyl acids such as perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) have applications in numerous industrial and consumer products. Although the toxicology of some of these compounds has been investigated in the past, the widespread pr...

  20. Metabolic engineering of yeast to produce fatty acid-derived biofuels: bottlenecks and solutions.

    PubMed

    Sheng, Jiayuan; Feng, Xueyang

    2015-01-01

    Fatty acid-derived biofuels can be a better solution than bioethanol to replace petroleum fuel, since they have similar energy content and combustion properties as current transportation fuels. The environmentally friendly microbial fermentation process has been used to synthesize advanced biofuels from renewable feedstock. Due to their robustness as well as the high tolerance to fermentation inhibitors and phage contamination, yeast strains such as Saccharomyces cerevisiae and Yarrowia lipolytica have attracted tremendous attention in recent studies regarding the production of fatty acid-derived biofuels, including fatty acids, fatty acid ethyl esters, fatty alcohols, and fatty alkanes. However, the native yeast strains cannot produce fatty acids and fatty acid-derived biofuels in large quantities. To this end, we have summarized recent publications in this review on metabolic engineering of yeast strains to improve the production of fatty acid-derived biofuels, identified the bottlenecks that limit the productivity of biofuels, and categorized the appropriate approaches to overcome these obstacles. PMID:26106371

  1. Metabolic engineering of yeast to produce fatty acid-derived biofuels: bottlenecks and solutions

    PubMed Central

    Sheng, Jiayuan; Feng, Xueyang

    2015-01-01

    Fatty acid-derived biofuels can be a better solution than bioethanol to replace petroleum fuel, since they have similar energy content and combustion properties as current transportation fuels. The environmentally friendly microbial fermentation process has been used to synthesize advanced biofuels from renewable feedstock. Due to their robustness as well as the high tolerance to fermentation inhibitors and phage contamination, yeast strains such as Saccharomyces cerevisiae and Yarrowia lipolytica have attracted tremendous attention in recent studies regarding the production of fatty acid-derived biofuels, including fatty acids, fatty acid ethyl esters, fatty alcohols, and fatty alkanes. However, the native yeast strains cannot produce fatty acids and fatty acid-derived biofuels in large quantities. To this end, we have summarized recent publications in this review on metabolic engineering of yeast strains to improve the production of fatty acid-derived biofuels, identified the bottlenecks that limit the productivity of biofuels, and categorized the appropriate approaches to overcome these obstacles. PMID:26106371

  2. Utilization of acidic α-amino acids as acyl donors: an effective stereo-controllable synthesis of aryl-keto α-amino acids and their derivatives.

    PubMed

    Wang, Lei; Murai, Yuta; Yoshida, Takuma; Okamoto, Masashi; Tachrim, Zetryana Puteri; Hashidoko, Yasuyuki; Hashimoto, Makoto

    2014-05-16

    Aryl-keto-containing α-amino acids are of great importance in organic chemistry and biochemistry. They are valuable intermediates for the construction of hydroxyl α-amino acids, nonproteinogenic α-amino acids, as well as other biofunctional components. Friedel-Crafts acylation is an effective method to prepare aryl-keto derivatives. In this review, we summarize the preparation of aryl-keto containing α-amino acids by Friedel-Crafts acylation using acidic α-amino acids as acyl-donors and Lewis acids or Brönsted acids as catalysts.

  3. 40 CFR 721.6110 - Alkyldi(alkyloxyhydroxypropyl) derivative, phosphoric acid esters, potassium salts.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...) derivative, phosphoric acid esters, potassium salts. (a) Chemical substance and significant new uses subject...) derivative, phosphoric acid esters, potassium salts. 721.6110 Section 721.6110 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF...

  4. 40 CFR 721.6110 - Alkyldi(alkyloxyhydroxypropyl) derivative, phosphoric acid esters, potassium salts.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...) derivative, phosphoric acid esters, potassium salts. (a) Chemical substance and significant new uses subject...) derivative, phosphoric acid esters, potassium salts. 721.6110 Section 721.6110 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF...

  5. 40 CFR 721.6110 - Alkyldi(alkyloxyhydroxypropyl) derivative, phosphoric acid esters, potassium salts.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...) derivative, phosphoric acid esters, potassium salts. (a) Chemical substance and significant new uses subject...) derivative, phosphoric acid esters, potassium salts. 721.6110 Section 721.6110 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF...

  6. Salicylic acid and some of its derivatives as antibacterial agents for viscose fabric.

    PubMed

    Kantouch, A; El-Sayed, A Atef; Salama, M; El-Kheir, A Abou; Mowafi, S

    2013-11-01

    Salicylic acid and three of its derivatives were used to provide antibacterial properties to viscose fabrics. The four bactericides used were bonded to the viscose fabrics using epichlorohydrin or polymer binders. Optimization of the salicylic acid and its derivatives as well as the concentration of polymers was reported. The ability of the polymer binders to attract and bind the four bactericides was observed. The overall results show that the antibacterial reactivity of salicylic acid and its derivatives are in the following order 5-bromosalicylic acid>salicylic acid>5-chlorosalicylic acid>4-chlorosalicylic acid. Using epichlorohydrin as a binding agent, unfortunately, inhibits the bactericidal activity of the four bactericides. The FTIR study concludes that the reaction between salicylic acid as well as its derivatives with epichlorohydrin takes place through the phenolic group of the acids. The unexpected deterioration in the bactericidal properties of salicylic acid and its derivatives as a result of the treatment with epichlorohydrin could be due to the nature of interaction between the epichlorohydrin molecule and the acids molecules. PVP and PU show superior ability to sustain the four bactericides used even after 10 washing cycles.

  7. Salicylic acid and some of its derivatives as antibacterial agents for viscose fabric.

    PubMed

    Kantouch, A; El-Sayed, A Atef; Salama, M; El-Kheir, A Abou; Mowafi, S

    2013-11-01

    Salicylic acid and three of its derivatives were used to provide antibacterial properties to viscose fabrics. The four bactericides used were bonded to the viscose fabrics using epichlorohydrin or polymer binders. Optimization of the salicylic acid and its derivatives as well as the concentration of polymers was reported. The ability of the polymer binders to attract and bind the four bactericides was observed. The overall results show that the antibacterial reactivity of salicylic acid and its derivatives are in the following order 5-bromosalicylic acid>salicylic acid>5-chlorosalicylic acid>4-chlorosalicylic acid. Using epichlorohydrin as a binding agent, unfortunately, inhibits the bactericidal activity of the four bactericides. The FTIR study concludes that the reaction between salicylic acid as well as its derivatives with epichlorohydrin takes place through the phenolic group of the acids. The unexpected deterioration in the bactericidal properties of salicylic acid and its derivatives as a result of the treatment with epichlorohydrin could be due to the nature of interaction between the epichlorohydrin molecule and the acids molecules. PVP and PU show superior ability to sustain the four bactericides used even after 10 washing cycles. PMID:24076193

  8. Hydroxyoctadecadienoic acids: Oxidised derivatives of linoleic acid and their role in inflammation associated with metabolic syndrome and cancer.

    PubMed

    Vangaveti, Venkat N; Jansen, Holger; Kennedy, Richard Lee; Malabu, Usman H

    2016-08-15

    Linoleic acid (LA) is a major constituent of low-density lipoproteins. An essential fatty acid, LA is a polyunsaturated fatty acid, which is oxidised by endogenous enzymes and reactive oxygen species in the circulation. Increased levels of low-density lipoproteins coupled with oxidative stress and lack of antioxidants drive the oxidative processes. This results in synthesis of a range of oxidised derivatives, which play a vital role in regulation of inflammatory processes. The derivatives of LA include, hydroxyoctadecadienoic acids, oxo-​octadecadienoic acids, epoxy octadecadecenoic acid and epoxy-keto-octadecenoic acids. In this review, we examine the role of LA derivatives and their actions on regulation of inflammation relevant to metabolic processes associated with atherogenesis and cancer. The processes affected by LA derivatives include, alteration of airway smooth muscles and vascular wall, affecting sensitivity to pain, and regulating endogenous steroid hormones associated with metabolic syndrome. LA derivatives alter cell adhesion molecules, this initial step, is pivotal in regulating inflammatory processes involving transcription factor peroxisome proliferator-activated receptor pathways, thus, leading to alteration of metabolic processes. The derivatives are known to elicit pleiotropic effects that are either beneficial or detrimental in nature hence making it difficult to determine the exact role of these derivatives in the progress of an assumed target disorder. The key may lie in understanding the role of these derivatives at various stages of development of a disorder. Novel pharmacological approaches in altering the synthesis or introduction of synthesised LA derivatives could possibly help drive processes that could regulate inflammation in a beneficial manner. Chemical Compounds: Linoleic acid (PubChem CID: 5280450), 9- hydroxyoctadecadienoic acid (PubChem CID: 5312830), 13- hydroxyoctadecadienoic acid (PubChem CID: 6443013), 9-oxo

  9. Polymerized fatty acid amine derivatives useful as friction and wear-reducing additives

    SciTech Connect

    Coupland, K.; Smith, C.R.

    1981-02-10

    A hydrocarbon composition having a major portion of a hydrocarbon preferably a lubricating oil such as mineral oil and at least a friction-reducing amount usually 0.01 to 10 weight percent of an amine or amine derivative of a hydrocarbon-soluble polymerized fatty acid e.g. a dimeramine derived from a dicarboxylic acid containing at least 12 carbon atoms such as 9(10)-carboxy stearic acid has improved antifriction and flue economy properties.

  10. Distillation of natural fatty acids and their chemical derivatives

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Well over 1,000 different fatty acids are known which are natural components of fats, oils (triacylglycerols), and other related compounds. These fatty acids can have different alkyl chain lengths, 0-6 carbon-carbon double bonds possessing cis- or trans-geometry, and can contain a variety of functio...

  11. Production and applications of carbohydrate-derived sugar acids as generic biobased chemicals.

    PubMed

    Mehtiö, Tuomas; Toivari, Mervi; Wiebe, Marilyn G; Harlin, Ali; Penttilä, Merja; Koivula, Anu

    2016-10-01

    This review considers the chemical and biotechnological synthesis of acids that are obtained by direct oxidation of mono- or oligosaccharide, referred to as sugar acids. It focuses on sugar acids which can be readily derived from plant biomass sources and their current and future applications. The three main classes of sugar acids are aldonic, aldaric and uronic acids. Interest in organic acids derived from sugars has recently increased, as part of the interest to develop biorefineries which produce not only biofuels, but also chemicals to replace those currently derived from petroleum. More than half of the most desirable biologically produced platform chemicals are organic acids. Currently, the only sugar acid with high commercial production is d-gluconic acid. However, other sugar acids such as d-glucaric and meso-galactaric acids are being produced at a lower scale. The sugar acids have application as sequestering agents and binders, corrosion inhibitors, biodegradable chelators for pharmaceuticals and pH regulators. There is also considerable interest in the use of these molecules in the production of synthetic polymers, including polyamides, polyesters and hydrogels. Further development of these sugar acids will lead to higher volume production of the appropriate sugar acids and will help support the next generation of biorefineries.

  12. Cinnamic acid and its derivatives inhibit fructose-mediated protein glycation.

    PubMed

    Adisakwattana, Sirichai; Sompong, Weerachat; Meeprom, Aramsri; Ngamukote, Sathaporn; Yibchok-Anun, Sirintorn

    2012-01-01

    Cinnamic acid and its derivatives have shown a variety of pharmacologic properties. However, little is known about the antiglycation properties of cinnamic acid and its derivatives. The present study sought to characterize the protein glycation inhibitory activity of cinnamic acid and its derivatives in a bovine serum albumin (BSA)/fructose system. The results demonstrated that cinnamic acid and its derivatives significantly inhibited the formation of advanced glycation end products (AGEs) by approximately 11.96-63.36% at a concentration of 1 mM. The strongest inhibitory activity against the formation of AGEs was shown by cinnamic acid. Furthermore, cinnamic acid and its derivatives reduced the level of fructosamine, the formation of N(ɛ)-(carboxymethyl) lysine (CML), and the level of amyloid cross β-structure. Cinnamic acid and its derivatives also prevented oxidative protein damages, including effects on protein carbonyl formation and thiol oxidation of BSA. Our findings may lead to the possibility of using cinnamic acid and its derivatives for preventing AGE-mediated diabetic complications.

  13. Sophorolipid-derived unsaturated and epoxy fatty acid estolides as plasticizers for poly(3-hydroxybutyrate)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Unsaturated and epoxy fatty acid estolides were synthesized from the omega and omega-1 hydroxy fatty acids derived from sophorolipids (SLs) prepared by fermentation from glucose:soybean oil and glucose:oleic acid, respectively. These estolides were utilized as additives in solution-cast poly(3-hydro...

  14. Endothelial Differentiation of Human Adipose-Derived Stem Cells on Polyglycolic Acid/Polylactic Acid Mesh.

    PubMed

    Deng, Meng; Gu, Yunpeng; Liu, Zhenjun; Qi, Yue; Ma, Gui E; Kang, Ning

    2015-01-01

    Adipose-derived stem cell (ADSC) is considered as a cell source potentially useful for angiogenesis in tissue engineering and regenerative medicine. This study investigated the growth and endothelial differentiation of human ADSCs on polyglycolic acid/polylactic acid (PGA/PLA) mesh compared to 2D plastic. Cell adhesion, viability, and distribution of hADSCs on PGA/PLA mesh were observed by CM-Dil labeling, live/dead staining, and SEM examination while endothelial differentiation was evaluated by flow cytometry, Ac-LDL/UEA-1 uptake assay, immunofluorescence stainings, and gene expression analysis of endothelial related markers. Results showed hADSCs gained a mature endothelial phenotype with a positive ratio of 21.4 ± 3.7% for CD31+/CD34- when induced in 3D mesh after 21 days, which was further verified by the expressions of a comprehensive range of endothelial related markers, whereas hADSCs in 2D induced and 2D/3D noninduced groups all failed to differentiate into endothelial cells. Moreover, compared to 2D groups, the expression for α-SMA was markedly suppressed in 3D cultured hADSCs. This study first demonstrated the endothelial differentiation of hADSCs on the PGA/PLA mesh and pointed out the synergistic effect of PGA/PLA 3D culture and growth factors on the acquisition of mature characteristic endothelial phenotype. We believed this study would be the initial step towards the generation of prevascularized tissue engineered constructs.

  15. Phenolic acid metabolites as biomarkers for tea- and coffee-derived polyphenol exposure in human subjects.

    PubMed

    Hodgson, Jonathan M; Chan, Shin Yee; Puddey, Ian B; Devine, Amanda; Wattanapenpaiboon, Naiyana; Wahlqvist, Mark L; Lukito, Widjaja; Burke, Valerie; Ward, Natalie C; Prince, Richard L; Croft, Kevin D

    2004-02-01

    Tea and coffee are rich in polyphenols with a variety of biological activities. Many of the demonstrated activities are consistent with favourable effects on the risk of chronic diseases. 4-O-methylgallic acid (4OMGA) and isoferulic acid are potential biomarkers of exposure to polyphenols derived from tea and coffee respectively. 4OMGA is derived from gallic acid in tea, and isoferulic acid is derived from chlorogenic acid in coffee. Our major objective was to explore the relationships of tea and coffee intake with 24 h urinary excretion of 4OMGA and isoferulic acid in human subjects. The relationships of long-term usual (111 participants) and contemporaneously recorded current (344 participants) tea and coffee intake with 24 h urinary excretion of 4OMGA and isoferulic acid were assessed in two populations. 4OMGA was related to usual (r 0.50, P<0.001) and current (r 0.57, P<0.001) tea intake, and isoferulic acid was related to usual (r 0.26, P=0.008) and current (r 0.18, P<0.001) coffee intake. Overall, our present results are consistent with the proposal that 4OMGA is a good biomarker for black tea-derived polyphenol exposure, but isoferulic acid may be of limited usefulness as a biomarker for coffee-derived polyphenol exposure.

  16. Novel biomarkers of the metabolism of caffeic acid derivatives in vivo.

    PubMed

    Rechner, A R; Spencer, J P; Kuhnle, G; Hahn, U; Rice-Evans, C A

    2001-06-01

    The purpose of this study was to investigate biomarkers of the bioavailability and metabolism of hydroxycinnamate derivatives through the determination of the pharmacokinetics of their urinary elimination and identification of the metabolites excreted. Coffee was used as a rich source of caffeic acid derivatives and human supplementation was undertaken. The results show a highly significant increase in the excretion of ferulic, isoferulic, dihydroferulic acid (3-(4-hydroxy-3-methoxyphenyl)-propionic acid), and vanillic acid postsupplementation relative to the levels presupplementation. Thus, ferulic, isoferulic, and dihydroferulic acids are specific biomarkers for the bioavailability and metabolism of dietary caffeic acid esters. Isoferulic acid is a unique biomarker as it is not a dietary component, however, dihydroferulic acid may well derive from other flavonoids with a structurally related B-ring. 3-Hydroxyhippuric acid has also been identified as an indicator for bioavailability and metabolism of phenolic compounds, and shows a highly significant excretion increase postsupplementation. The results reveal isoferulic acid (and possibly dihydroferulic acid) as novel markers of caffeoyl quinic acid metabolism.

  17. [Phenolic acid derivatives from Bauhinia glauca subsp. pernervosa].

    PubMed

    Zhao, Qiao-Li; Wu, Zeng-Bao; Zheng, Zhi-Hui; Lu, Xin-Hua; Liang, Hong; Cheng, Wei; Zhang, Qing-Ying; Zhao, Yu-Ying

    2011-08-01

    To study the chemical constituents of Bauhinia glauca subsp. pernervosa, eleven phenolic acids were isolated from a 95% ethanol extract by using a combination of various chromatographic techniques including column chromatography over silica gel, ODS, MCI, Sephadex LH-20, and semi-preparative HPLC. By spectroscopic techniques including 1H NMR, 13C NMR, 2D NMR, and HR-ESI-MS, these compounds were identified as isopropyl O-beta-(6'-O-galloyl)-glucopyranoside (1), ethyl O-beta-(6'-O-galloyl)-glucopyranoside (2), 3, 4, 5-trimethoxyphenyl-(6'-O-galloyl)-O-beta-D-glucopyranoside (3), 3, 4, 5-trimethoxyphenyl-beta-D-glucopyranoside (4), gallic acid (5), methyl gallate (6), ethyl gallate (7), protocatechuic acid (8), 3, 5-dimethoxy-4-hydroxybenzoic acid (9), erigeside C (10) and glucosyringic acid (11). Among them, compound 1 is a new polyhydroxyl compound; compounds 2, 10, and 11 were isolated from the genus Bauhinia for the first time, and the other compounds were isolated from the plant for the first time. Compounds 6 and 8 showed significant protein tyrosine phosphatase1B (PTP1B) inhibitory activity in vitro with the IC50 values of 72.3 and 54.1 micromol x L(-1), respectively.

  18. Azorhodanine derivatives as inhibitors for acidic corrosion of nickel.

    PubMed

    Fouda, Abd El-Aziz S; Al-Sarawy, Ahmed A; Omar, Tark M

    2005-01-01

    Azorhodanine derivatives (HL1-HL5) were tested as corrosion inhibitors for nickel in 2M HNO3 solution using weight loss and galvanostatic polarization techniques. The results showed that these derivatives act as inhibitors for nickel in this medium. The inhibition was assumed to occur via adsorption of the inhibitor molecule on the metal surface. Polarization measurements indicated that these compounds act as mixed-type inhibitors, but the cathode is more polarized when an external current was applied. This means that these compounds retard the rate of hydrogen evolution and the rate of dissolution of the metal. Results showed that azorhodanine derivatives are adsorbed on the nickel surface following Temkin's adsorption isotherm. The activation energy and thermodynamic parameters were calculated and discussed at different temperatures (30-45 degrees C).

  19. Pseudoephedrine-Directed Asymmetric α-Arylation of α-Amino Acid Derivatives.

    PubMed

    Atkinson, Rachel C; Fernández-Nieto, Fernando; Mas Roselló, Josep; Clayden, Jonathan

    2015-07-27

    Available α-amino acids undergo arylation at their α position in an enantioselective manner on treatment with base of N'-aryl urea derivatives ligated to pseudoephedrine as a chiral auxiliary. In situ silylation and enolization induces diastereoselective migration of the N'-aryl group to the α position of the amino acid, followed by ring closure to a hydantoin with concomitant explulsion of the recyclable auxiliary. The hydrolysis of the hydantoin products provides derivatives of quaternary amino acids. The arylation avoids the use of heavy-metal additives, and is successful with a range of amino acids and with aryl rings of varying electronic character.

  20. Endothelial Differentiation of Human Adipose-Derived Stem Cells on Polyglycolic Acid/Polylactic Acid Mesh

    PubMed Central

    Deng, Meng; Gu, Yunpeng; Liu, Zhenjun; Qi, Yue; Ma, Gui E.; Kang, Ning

    2015-01-01

    Adipose-derived stem cell (ADSC) is considered as a cell source potentially useful for angiogenesis in tissue engineering and regenerative medicine. This study investigated the growth and endothelial differentiation of human ADSCs on polyglycolic acid/polylactic acid (PGA/PLA) mesh compared to 2D plastic. Cell adhesion, viability, and distribution of hADSCs on PGA/PLA mesh were observed by CM-Dil labeling, live/dead staining, and SEM examination while endothelial differentiation was evaluated by flow cytometry, Ac-LDL/UEA-1 uptake assay, immunofluorescence stainings, and gene expression analysis of endothelial related markers. Results showed hADSCs gained a mature endothelial phenotype with a positive ratio of 21.4 ± 3.7% for CD31+/CD34− when induced in 3D mesh after 21 days, which was further verified by the expressions of a comprehensive range of endothelial related markers, whereas hADSCs in 2D induced and 2D/3D noninduced groups all failed to differentiate into endothelial cells. Moreover, compared to 2D groups, the expression for α-SMA was markedly suppressed in 3D cultured hADSCs. This study first demonstrated the endothelial differentiation of hADSCs on the PGA/PLA mesh and pointed out the synergistic effect of PGA/PLA 3D culture and growth factors on the acquisition of mature characteristic endothelial phenotype. We believed this study would be the initial step towards the generation of prevascularized tissue engineered constructs. PMID:26106426

  1. Technetium radiodiagnostic fatty acids derived from bisamide bisthiol ligands

    DOEpatents

    Jones, Alun G.; Lister-James, John; Davison, Alan

    1988-05-24

    A bisamide-bisthiol ligand containing fatty acid substituted thiol useful for producing Tc-labelled radiodiagnostic imaging agents is described. The ligand forms a complex with the radionuclide .sup.99m Tc suitable for administration as a radiopharmaceutical to obtain images of the heart for diagnosis of myocardial disfunction.

  2. Actions of derivatives of lysergic acid on the heart of venus mercenaria

    PubMed Central

    Wright, Anne McCoy; Moorhead, Merilyn; Welsh, J. H.

    1962-01-01

    5-Hydroxytryptamine and a number of (+)-lysergic acid derivatives have been tested on the heart of Venus mercenaria. One group of derivatives was found to increase the amplitude and frequency of heart beat in a manner much like 5-hydroxytryptamine. It included the monoethylamide, diethylamide, propanolamide (ergometrine), butanolamide (methylergometrine) and certain peptide derivatives of lysergic acid without substituents in positions 1 or 2. Of these, lysergic acid diethylamide was the most active. Given sufficient time (up to 4 hr), as little as 10 ml. of 10-16 M lysergic acid diethylamide produced a maximum increase in amplitude and frequency in about one-half of the 80 hearts on which it was tested. Its action was very slowly reversed by washing, as was true of all lysergic acid derivatives. A second group of lysergic acid derivatives, substituted in positions 1 or 2, had weak excitor action, if any, and specific 5-hydroxytryptamine blocking action. This group consisted of 1-methyl-, 1-acetyl-, and 2-bromo-lysergic acid diethylamide and 1-methyllysergic acid butanolamide (methysergide). Of these, the last showed least signs of excitor action, usually none up to 10-4 M, and it blocked 5-hydroxytryptamine in a molar ratio of about one to one. PMID:14008412

  3. Rhodium-catalyzed asymmetric addition of arylboronic acids to cyclic N-sulfonyl ketimines towards the synthesis of α,α-diaryl-α-amino acid derivatives.

    PubMed

    Takechi, Ryosuke; Nishimura, Takahiro

    2015-05-01

    Rhodium/chiral diene complex-catalyzed asymmetric addition of arylboronic acids to cyclic ketimines having an ester group proceeded to give the corresponding α-amino acid derivatives in high yields with high enantioselectivity. The cyclic amino acid derivative was transformed into a linear α,α-diaryl-substituted α-N-methylamino acid ester.

  4. Catalytic asymmetric protonation of lithium enolates using amino acid derivatives as chiral proton sources.

    PubMed

    Mitsuhashi, Kaori; Ito, Rie; Arai, Takayoshi; Yanagisawa, Akira

    2006-04-13

    [reaction: see text] Asymmetric protonation of lithium enolates was examined using commercially available amino acid derivatives as chiral proton sources. Among the amino acid derivatives tested, Nbeta-l-aspartyl-l-phenylalanine methyl ester was found to cause significant asymmetric induction in the protonation of lithium enolates. The enantiomeric excess (up to 88% ee) of the products obtained in the presence of a catalytic amount of the chiral proton source was higher than those obtained in the stoichiometric reaction. PMID:16597150

  5. Catalytic asymmetric protonation of lithium enolates using amino acid derivatives as chiral proton sources.

    PubMed

    Mitsuhashi, Kaori; Ito, Rie; Arai, Takayoshi; Yanagisawa, Akira

    2006-04-13

    [reaction: see text] Asymmetric protonation of lithium enolates was examined using commercially available amino acid derivatives as chiral proton sources. Among the amino acid derivatives tested, Nbeta-l-aspartyl-l-phenylalanine methyl ester was found to cause significant asymmetric induction in the protonation of lithium enolates. The enantiomeric excess (up to 88% ee) of the products obtained in the presence of a catalytic amount of the chiral proton source was higher than those obtained in the stoichiometric reaction.

  6. Graphene quantum dots as additives in capillary electrophoresis for separation cinnamic acid and its derivatives.

    PubMed

    Sun, Yaming; Bi, Qing; Zhang, Xiaoli; Wang, Litao; Zhang, Xia; Dong, Shuqing; Zhao, Liang

    2016-05-01

    A facile capillary electrophoresis (CE) method for the separation of cinnamic acid and its derivatives (3,4-dimethoxycinnamic acid, 4-methoxycinnamic acid, isoferulic acid, sinapic acid, cinnamic acid, ferulic acid, and trans-4-hydroxycinnamic acid) using graphene quantum dots (GQDs) as additives with direct ultraviolet (UV) detection is reported. GQDs were synthesized by chemical oxidization and further purified by a macroporous resin column to remove salts (Na2SO4 and NaNO3) and other impurities. Transmission electron microscopy (TEM) indicated that GQDs have a relatively uniform particle size (2.3 nm). Taking into account the structural features of GQDs, cinnamic acid and its derivatives were adopted as model compounds to investigate whether GQDs can be used to improve CE separations. The separation performance of GQDs used as additives in CE was studied through variations of pH, concentration of the background electrolyte (BGE), and contents of GQDs. The results indicated that excellent separation can be achieved in less than 18 min, which is mainly attributed to the interaction between the analytes and GQDs, especially isoferulic acid, sinapic acid, and cinnamic acid.

  7. Pd(II)-catalysed meta-C–H functionalizations of benzoic acid derivatives

    PubMed Central

    Li, Shangda; Cai, Lei; Ji, Huafang; Yang, Long; Li, Gang

    2016-01-01

    Benzoic acids are highly important structural motifs in drug molecules and natural products. Selective C–H bond functionalization of benzoic acids will provide synthetically useful tools for step-economical organic synthesis. Although direct ortho-C–H functionalizations of benzoic acids or their derivatives have been intensely studied, the ability to activate meta-C–H bond of benzoic acids or their derivatives in a general manner via transition-metal catalysis has been largely unsuccessful. Although chelation-assisted meta-C–H functionalization of electron-rich arenes was reported, chelation-assisted meta-C–H activation of electron-poor arenes such as benzoic acid derivatives remains a formidable challenge. Herein, we report a general protocol for meta-C–H olefination of benzoic acid derivatives using a nitrile-based sulfonamide template. A broad range of benzoic acid derivatives are meta-selectively olefinated using molecular oxygen as the terminal oxidant. The meta-C–H acetoxylation, product of which is further transformed at the meta-position, is also reported. PMID:26813919

  8. New ionic derivatives of betulinic acid as highly potent anti-cancer agents.

    PubMed

    Suresh, Challa; Zhao, Hua; Gumbs, Angelique; Chetty, Chellu S; Bose, Himangshu S

    2012-02-15

    Betulinic acid is a natural compound with high in vitro cytotoxicity toward many cancer cells. However, the poor water solubility of this compound hampers an effective in vivo cancer study. We prepared new ionic derivatives of betulinic acid with higher water solubilities, without losing the structural integrity and functionality of this compound. As a result, these new ionic derivatives have shown much higher inhibitory effects against different cancer cell lines such as melanoma A375, neuroblastoma SH-SY5Y and breast adenocarcinoma MCF7. For A375 cell lines, the derivative 5 exhibited a low IC(50) value of 36 μM (vs 154 μM for betulinic acid); for MCF7 cell lines, the derivative 5 also exhibited a low IC(50) value of 25 μM (vs 112 μM for betulinic acid). The high cytotoxicity of these new derivatives can be linked to their greatly improved water solubility. Our assay method used little DMSO in aiding the dissolution of these derivatives to demonstrate the advantage of improved water solubility and to mimic the in vivo study conditions. The cell viability studies based on both MTT and LDH assay methods have confirmed the high inhibitory effect of our ionic derivatives of betulinic acid (particularly 4 and 5) against different cancer cells.

  9. Simultaneous determination of acetylsalicylic and salicylic acids by first derivative spectrometry in pharmaceutical preparations

    NASA Astrophysics Data System (ADS)

    Rogić, Dunja

    1993-03-01

    A multicomponent first derivative UV spectrometric procedure for determination of acetylsalicylic acid (aspirin) and salicylic acid in the solution containing 1 % (w/v) of citric acid in some pharmaceutical preparations is presented. The method is based on the use of the first derivative minimum spectrometric measurements at 286 nm for aspirin and at 318 nm for salicylic acid. Four kinds of cmmercial Aspirin tablets were assayed without a long pretreatment of the pharmaceuticals from the tablet additives. Beer's law is obeyed from 13.62-68.1 μg ml -1 of aspirin and from 2.723-13.616 μg ml -1 of salicylic acid. Detection limits at the 0.05 level of significance were calculated to be 1.24 and 0.25 μg ml -1 with relative standard deviations of 1.09 % and 1.2 % of aspirin and salicylic acid, respectively.

  10. Visible-light-mediated chan-lam coupling reactions of aryl boronic acids and aniline derivatives.

    PubMed

    Yoo, Woo-Jin; Tsukamoto, Tatsuhiro; Kobayashi, Shū

    2015-05-26

    The copper(II)-catalyzed aerobic oxidative coupling reaction between aryl boronic acids and aniline derivatives was found to be improved significantly under visible-light-mediated photoredox catalysis. The substrate scope of this oxidative Chan-Lam reaction was thus expanded to include electron-deficient aryl boronic acids as viable starting materials.

  11. Catalytic Asymmetric Synthesis of anti-α,β-Diamino Acid Derivatives.

    PubMed

    Izumi, Sanae; Kobayashi, Yusuke; Takemoto, Yoshiji

    2016-02-19

    A novel approach to chiral anti-α,β-diamino acid derivatives through tandem orthogonal organocatalysis has been developed. Chiral phosphoric acid catalysts control the chemo-, regio-, and stereoselective addition of hydroxylamines to alkylideneoxazolones, while a phosphine catalyst promotes the isomerization of Z- alkylideneoxazolones to the more reactive E- alkylideneoxazolones.

  12. Formation of dopamine adducts derived from brain polyunsaturated fatty acids: mechanism for Parkinson disease.

    PubMed

    Liu, Xuebo; Yamada, Naruomi; Maruyama, Wakako; Osawa, Toshihiko

    2008-12-12

    Oxidative stress appears to be directly involved in the pathogenesis of the neurodegeneration of dopaminergic systems in Parkinson disease. In this study, we formed four dopamine modification adducts derived from docosahexaenoic acid (C22:6/omega-3) and arachidonic acid (C18:4/omega-6), which are known as the major polyunsaturated fatty acids in the brain. Upon incubation of dopamine with fatty acid hydroperoxides and an in vivo experiment using rat brain tissue, all four dopamine adducts were detected. Furthermore, hexanoyl dopamine (HED), an arachidonic acid-derived adduct, caused severe cytotoxicity in human dopaminergic neuroblastoma SH-SY5Y cells, whereas the other adducts were only slightly affected. The HED-induced cell death was found to include apoptosis, which also seems to be mediated by reactive oxygen species generation and mitochondrial abnormality. Additionally, the experiments using monoamine transporter inhibitor and mouse embryonic fibroblast NIH-3T3 cells that lack the monoamine transporter indicate that the HED-induced cytotoxicity might specially occur in the neuronal cells. These data suggest that the formation of the docosahexaenoic acid- and arachidonic acid-derived dopamine adducts in vitro and in vivo, and HED, the arachidonic acid-derived dopamine modification adduct, which caused selective cytotoxicity of neuronal cells, may indicate a novel mechanism responsible for the pathogenesis in Parkinson disease.

  13. Mass spectral analysis of C3 and C4 aliphatic amino acid derivatives.

    NASA Technical Reports Server (NTRS)

    Lawless, J. G.; Chadha, M. S.

    1971-01-01

    Diagnostic criteria are obtained for the distinction of alpha, beta, gamma, and N-methyl isomers of the C3 and C4 aliphatic amino acids, using mass spectral analysis of the derivatives of these acids. The use of deuterium labeling has helped in the understanding of certain fragmentation pathways.

  14. Synthesis and Anti-microbial Activity of Novel Phosphatidylethanolamine-N-amino Acid Derivatives.

    PubMed

    Vijeetha, Tadla; Balakrishna, Marrapu; Karuna, Mallampalli Sri Lakshmi; Surya Koppeswara Rao, Bhamidipati Venkata; Prasad, Rachapudi Badari Narayana; Kumar, Koochana Pranay; Surya Narayana Murthy, Upadyaula

    2015-01-01

    The study involved synthesis of five novel amino acid derivatives of phosphatidylethanolamine isolated from egg yolk lecithin employing a three step procedure i) N-protection of L-amino acids with BOC anhydride in alkaline medium ii) condensation of - CO2H group of N-protected amino acid with free -NH2 of PE by a peptide linkage and iii) deprotection of N-protected group of amino acids to obtain phosphatidylethanolamine-N-amino acid derivatives in 60-75% yield. The five L-amino acids used were L glycine, L-valine, L-leucine, L-isoleucine and L-phenylalanine. The amino acid derivatives were screened for anti-baterial activity against B. subtilis, S. aureus, P. aeroginosa and E. coli taking Streptomycin as reference compound and anti-fungal activity against C. albicans, S. cervisiae, A. niger taking AmphotericinB as reference compound. All the amino acid derivatives exhibited extraordinary anti-bacterial activities about 3 folds or comparable to Streptomycin and moderate or no anti-fungal activity against Amphotericin-B.

  15. Brønsted acid-catalyzed Nazarov cyclization of pyrrole derivatives accelerated by microwave irradiation.

    PubMed

    Bachu, Prabhakar; Akiyama, Takahiko

    2009-07-15

    The Brønsted acid-catalyzed Nazarov cyclization of pyrrole derivatives was developed. Microwave irradiation accelerated the Nazarov cyclization significantly at 40 degrees C to give cyclopenta[b]pyrrole derivatives in excellent yields with high trans selectivity. PMID:19447615

  16. A novel trans-4-hydroxycinnamic acid derivative from Meyer lemon (Citrus meyeri).

    PubMed

    Miyake, Yoshiaki; Ito, Chihiro; Itoigawa, Masataka

    2012-12-15

    Isolation and structural elucidation of a new trans-4-hydroxycinnamic acid derivative from Meyer lemon (Citrus meyeri hort. ex Y. Tanaka) was carried out. The derivative exhibited the antioxidative activity by ORAC (oxygen radical absorbance capacity) assay and was found in the flavedo and alvedo of Meyer lemon peel.

  17. Insulin-releasing properties of a series of cinnamic acid derivatives in vitro and in vivo.

    PubMed

    Adisakwattana, Sirichai; Moonsan, Preecha; Yibchok-Anun, Sirintorn

    2008-09-10

    Cinnamic acid derivatives are naturally occurring substances found in fruits, vegetables, and flowers and are consumed as dietary phenolic compounds. In the present study, cinnamic acid and its derivatives were evaluated for insulin secreting activity in perfused rat pancreas and pancreatic beta-cells (INS-1) as well as an increase in [Ca(2+)]i in vitro. The presence of m-hydroxy or p-methoxy residues on cinnamic acid was a significantly important substituent as an effective insulin releasing agent. The introduction of p-hydroxy and m-methoxy-substituted groups in cinnamic acid structure (ferulic acid) displayed the most potent insulin secreting agent among those of cinnamic acid derivatives. In particular, the stimulatory insulin secreting activities of test compounds were associated with a rise of [Ca(2+)]i in INS-1. In perfused rat pancreas, m-hydroxycinnamic acid, p-methoxycinnamic acid, and ferulic acid (100 microM) significantly stimulated insulin secretion during 10 min of administration. The onset time of insulin secretion of those compounds was less than 1 min and reached its peak at 4 min that was about 2.8-, 3.3-, and 3.4-fold of the baseline level, respectively. Intravenous administration of p-methoxycinnamic acid and ferulic acid (5 mg/kg) significantly decreased plasma glucose and increased insulin concentration in normal rats and maintained its level for 15 min until the end of experiment. Meanwhile, m-hydroxycinnamic acid induced a significant lowering of plasma glucose after 6 min, but the effects were transient with plasma glucose concentration, rapidly returning to basal levels. Our findings suggested that p-methoxycinnamic acid and ferulic acid may be beneficial for the treatment of diabetes mellitus because they regulated blood glucose level by stimulating insulin secretion from pancreatic beta-cells.

  18. ESR study of the photochemistry of benzoic acid derivatives

    SciTech Connect

    Jeevarajan, A.S.; Fessenden, R.W. )

    1992-12-16

    Electron spin resonance (ESR) has been used to study radical intermediates in the photochemistry of a number of aromatic carboxylic acids, esters, anhydrides, amides, imides, and nitriles. Continuous photolysis was used to produce the radicals in either aqueous or alcoholic media. The triplet states of the compounds undergo two reactions in the presence of a hydrogen donor such as 2-propanol. A hydrogen atom is transferred to certain carbon atoms of the aromatic ring forming cyclohexadienyl radicals. In most cases, addition occurs at or opposite the carboxyl (or cyano) group. The pattern of addition is attributed to the higher spin density in the triplet at those positions. This pattern also correlates with the positions of higher hyperfine splitting in the corresponding anion radicals. In a parallel reaction, a hydrogen atom is also transferred to an oxygen of the carboxyl group (for acids, anhydrides, and esters) to form the one-electron-reduction product. The cyclohexadienyl radicals are not formed by protonation on a carbon of an anion radical. The ESR spectra of most of the cyclohexadienyl radicals are highly polarized to the extent that the low-field lines appear in emission. This effect is believed to be normal chemically induced dynamic spin polarization (CIDEP) as a result of cross reactions with the other radicals present. 46 refs., 7 figs., 10 tabs.

  19. HYPERSENSITIVITY TO PENICILLENIC ACID DERIVATIVES IN HUMAN BEINGS WITH PENICILLIN ALLERGY

    PubMed Central

    Parker, Charles W.; Shapiro, Jack; Kern, Milton; Eisen, Herman N.

    1962-01-01

    Multifunctional derivatives of penicillenic acid are effective elicitors of wheal-and-erythema skin responses in humans allergic to penicillin. Of the effective derivatives, penicilloyl-polylysines are particularly attractive as skin test reagents because they appear to be incapable of inducing antibody formation. The skin responses are specifically inhibitable in most instances by homologous unifunctional haptens. The penicillenic acid derivatives which appear to be determinants of human allergic reactions to penicillin are: penicilloyl, penicillenate, and groups of the penamaldate-penilloaldehyde type. Of these, the most significant appears to be the penicilloyl-lysyl determinant. PMID:14483916

  20. Treatment of acne vulgaris with the retinoic acid derivative Ro 11-1430. A controlled clinical trial against retinoic acid.

    PubMed

    Christiansen, J; Holm, P; Reymann, F

    1976-01-01

    In a double-blind, randomized, group-comparative clinical trial, 31 patients with acne vulgaris received topical treatment for 6-8 weeks with a lotion containing either 0.05% retinoic acid or 0.1% of the retinoic acid derivative Ro 11-1430. The side-effects erythema, desquamation and burning were significantly less frequent with Ro 11-1430 than with retinoic acid. The treatments appeared to be approximately equally effective in reducing the number of acne elements, but due to the limited number of patients studied, the trial was admittedly not sufficient to detect differences with regard to therapeutic efficacy.

  1. Decay resistance of wood treated with boric acid and tall oil derivates.

    PubMed

    Temiz, Ali; Alfredsen, Gry; Eikenes, Morten; Terziev, Nasko

    2008-05-01

    In this study, the effect of two boric acid concentrations (1% and 2%) and four derivates of tall oil with varying chemical composition were tested separately and in combination. The tall oil derivates were chosen in a way that they consist of different amounts of free fatty, resin acids and neutral compounds. Decay tests using two brown rot fungi (Postia placenta and Coniophora puteana) were performed on both unleached and leached test samples. Boric acid showed a low weight loss in test samples when exposed to fungal decay before leaching, but no effect after leaching. The tall oil derivates gave better efficacy against decay fungi compared to control, but are not within the range of the efficacy needed for a wood preservative. Double impregnation with boric acid and tall oil derivates gave synergistic effects for several of the double treatments both in unleached and leached samples. In the unleached samples the double treatment gave a better efficacy against decay fungi than tall oil alone. In leached samples a better efficacy against brown rot fungi were achieved than in samples with boron alone and a nearly similar or better efficacy than for tall oil alone. Boric acid at 2% concentration combined with the tall oil derivate consisting of 90% free resin acids (TO-III) showed the best performance against the two decay fungi with a weight loss less than 3% after a modified pure culture test.

  2. Synthesis and preliminary biological evaluations of (+)-isocampholenic acid-derived amides.

    PubMed

    Grošelj, Uroš; Golobič, Amalija; Knez, Damijan; Hrast, Martina; Gobec, Stanislav; Ričko, Sebastijan; Svete, Jurij

    2016-08-01

    The synthesis of two novel (+)-isocampholenic acid-derived amines has been realized starting from commercially available (1S)-(+)-10-camphorsulfonic acid. The novel amines as well as (+)-isocampholenic acid have been used as building blocks in the construction of a library of amides using various aliphatic, aromatic, and amino acid-derived coupling partners using BPC and CDI as activating agents. Amide derivatives have been assayed against several enzymes that hold potential for the development of new drugs to battle bacterial infections and Alzheimer's disease. Compounds 20c and 20e showed promising selective sub-micromolar inhibition of human butyrylcholinesterase [Formula: see text] ([Formula: see text] values [Formula: see text] and [Formula: see text], respectively). PMID:27017352

  3. Synthesis, structure, and biological applications of α-fluorinated β-amino acids and derivatives.

    PubMed

    March, Taryn L; Johnston, Martin R; Duggan, Peter J; Gardiner, James

    2012-11-01

    This review gives a broad overview of the state of play with respect to the synthesis, conformational properties, and biological activity of α-fluorinated β-amino acids and derivatives. General methods are described for the preparation of monosubstituted α-fluoro-β-amino acids (Scheme 1). Nucleophilic methods for the introduction of fluorine predominantly involve the reaction of DAST with alcohols derived from α-amino acids, whereas electrophilic sources of fluorine such as NFSI have been used in conjunction with Arndt-Eistert homologation, conjugate addition or organocatalyzed Mannich reactions. α,α-Difluoro-β-amino acids have also been prepared using DAST; however, this area of synthesis is largely dominated by the use of difluorinated Reformatsky reagents to introduce the difluoro ester functionality (Scheme 9). α-Fluoro-β-amino acids and derivatives analyzed by X-ray crystal and NMR solution techniques are found to adopt preferred conformations which are thought to result from stereoelectronic effects associated with F located close to amines, amides, and esters (Figs. 2-6). α-Fluoro amide and β-fluoro ethylamide/amine effects can influence the secondary structure of α-fluoro-β-amino acid-containing derivatives including peptides and peptidomimetics (Figs. 7-9). α-Fluoro-β-amino acids are also components of a diverse range of bioactive anticancer (e.g., 5-fluorouracil), antifungal, and antiinsomnia agents as well as protease inhibitors where such fluorinated analogs have shown increased potency and spectrum of activity.

  4. Hydroxycinnamic Acid Derivatives Obtained from a Commercial Crataegus Extract and from Authentic Crataegus spp.§

    PubMed Central

    Kuczkowiak, Ulrich; Petereit, Frank; Nahrstedt, Adolf

    2014-01-01

    Abstract Eleven hydroxycinnamic acid derivatives were isolated from a 70% methanolic Crataegus extract (Crataegi folium cum flore) and partly verified and quantified for individual Crataegus species (C. laevigata, C. monogyna, C. nigra, C. pentagyna) by HPLC: 3-O-(E)-p-coumaroylquinic acid (1), 5-O-(E)-p-coumaroyl-quinic acid (2), 4-O-(E)-p-coumaroylquinic acid (3), 3-O-(E)-caffeoylquinic acid (4), 4-O-(E)-caffeoylquinic acid (5), 5-O-(E)-caffeoylquinic acid (6), 3,5-di-O-(E)-caffeoylquinic acid (7), 4,5-di-O-(E)-caffeoylquinic acid (8), (-)-2-O-(E)-caffeoyl-L-threonic acid (9), (-)-4-O-(E)-caffeoyl-L-threonic acid (10), and (-)-4-O-(E)-p-coumaroyl-L-threonic acid (11). Further, (-)-2-O-(E)-caffeoyl-D-malic acid (12) was isolated from C. submollis and also identified for C. pentagyna and C. nigra by co-chromatography. The isolates 10 and 11 were not found in the authentic fresh specimen, indicating that they may be formed during extraction by acyl migration from the 2-O-acylderivatives. Also, 9 and 11 are described here for the first time. All structures were assigned on the basis of their spectroscopic data (1H-, 13C-NMR, MS, optical rotation). PMID:26171328

  5. Synthesis and evaluation of new quinazolone derivatives of nalidixic acid as potential antibacterial and antifungal agents.

    PubMed

    Grover, Gaurav; Kini, Suvarna G

    2006-02-01

    In continuation of our work on synthesis of biheterocycles carrying the biodynamic heterocyclic systems at position 3, a series of new nalidixic acid derivatives having quinazolones moiety were synthesised to achieve enhanced biological activity and wide spectrum of activity. Nalidixic acid was first converted into its acid chloride using thionyl chloride as an acylating agent at laboratory temperature. Later it was converted to methyl ester. Nalidixoyl chloride formed vigorously reacts with methanol to give a methyl ester of nalidixic acid. The ester on addition of hydrazine hydrate furnished nalidixic acid hydrazide. Appropriate anthranilic acid was refluxed with acetic anhydride to form Benzoxazine/Acetanthranil. 5-iodo-derivative of anthranilic acid was prepared and also utilised to obtain 6-iodo-Benzoxazine/Acetanthranil. Also, 6-nitro-Benzoxazine/Acetanthranil was obtained by nitration of acetanthranil using conc. H(2)SO(4) and fuming HNO(3). Equimolar proportions of the appropriate synthesised acetanthranils and nalidixic acid hydrazide in the presence of ethanol were refluxed to synthesise quinazolones. Elemental analysis and IR spectra confirmed nalidixic acid hydrazide formation. The structures of the compounds obtained have been established on the basis of Spectral (IR, (1)H NMR and mass) data. The current study also involves in vitro antimicrobial screening (using Agar dilution and Punch well diffusion method) of synthesised quinazolone derivatives bearing nalidixic acid moiety on randomly collected microbial strains. The derivatives Ga (NAH), Gb (QN) and Gd (NiQNA) showed marked inhibitory activity against enteric pathogen like Aeromonas hydrophila, a causative agent of diarrhoea in both children as well as adults. Among the respiratory pathogens included in study, derivative Gd (NiQNA) was found to be active against Streptococcus pyogenes. No significant inhibitory activity was seen by any of synthesised derivatives against Coagulase negative

  6. Identification and quantitation of new glutamic acid derivatives in soy sauce by UPLC/MS/MS.

    PubMed

    Frerot, Eric; Chen, Ting

    2013-10-01

    Glutamic acid is an abundant amino acid that lends a characteristic umami taste to foods. In fermented foods, glutamic acid can be found as a free amino acid formed by proteolysis or as a non-proteolytic derivative formed by microorganisms. The aim of the present study was to identify different structures of glutamic acid derivatives in a typical fermented protein-based food product, soy sauce. An acidic fraction was prepared with anion-exchange solid-phase extraction (SPE) and analyzed by UPLC/MS/MS and UPLC/TOF-MS. α-Glutamyl, γ-glutamyl, and pyroglutamyl dipeptides, as well as lactoyl amino acids, were identified in the acidic fraction of soy sauce. They were chemically synthesized for confirmation of their occurrence and quantified in the selected reaction monitoring (SRM) mode. Pyroglutamyl dipeptides accounted for 770 mg/kg of soy sauce, followed by lactoyl amino acids (135 mg/kg) and γ-glutamyl dipeptides (70 mg/kg). In addition, N-succinoylglutamic acid was identified for the first time in food as a minor compound in soy sauce (5 mg/kg).

  7. Efficient, chemical-catalytic approach to the production of 3-hydroxypropanoic acid by oxidation of biomass-derived levulinic acid with hydrogen peroxide.

    PubMed

    Wu, Linglin; Dutta, Saikat; Mascal, Mark

    2015-04-13

    3-Hydroxypropanoic acid (HPA), a precursor to acrylic acid, can be produced in high yield by oxidation of the biomass-derived platform chemical levulinic acid. While treatment of levulinic acid with H2 O2 under acidic conditions gives predominantly succinic acid, a remarkable reversal of selectivity is observed under basic conditions, leading either directly to HPA or, under modified conditions, initially to 3-(hydroperoxy)propanoic acid, which can be quantitatively hydrogenated to HPA. PMID:25736835

  8. Arachidonic acid metabolism in fibroblasts derived from canine myocardium

    SciTech Connect

    Weber, D.R.; Prescott, S.M.

    1986-03-05

    Canine fibroblasts from normal or healing infarcted myocardium were grown in culture. The cells were morphologically indistinguishable, but the doubling time of cells from healing myocardium was 39.6 +/- 3.5 hr whereas that of normals was 24 +/- 3.7 (n=5, p < .025). Fibroblasts incorporated (/sup 3/H)arachidonate (AA) into phospholipids. Calcium ionophore A23187 (10 ..mu..M) caused release and metabolism of (/sup 3/H) AA. A23187 or AA (10..mu..M) induced production of 6-keto PGF1..cap alpha.., PGE2, and a hydroxy metabolite of AA. RIA of 6-keto PGF1..cap alpha.. showed that subconfluent cells from healing myocardium produced 1202 +/- 354 pg/mg protein whereas that of normals was 551 +/- 222 (n=7, p < .025). Histamine and bradykinin also induced AA metabolism but were less potent. They examined the effect of AA released from deteriorating myocytes on AA metabolism by cultured fibroblasts. They confirmed that isolated myocytes labelled with (/sup 3/H)AA released but did not metabolize (/sup 3/H)AA. In coincubations, fibroblasts incorporated myocyte-derived AA. Subsequent stimulation of the fibroblasts with A23187 induced the synthesis of 6-keto PGF1..cap alpha.., PGE2 and a hydroxy metabolite. The fibroblast content of healing myocardium was 35-1000 times that of normal tissue (n=7). Thus even a moderate change in AA metabolism, amplified by the AA released from deteriorating myocytes, may be a significant physiologic or pathologic event.

  9. A biosynthetic pathway for a prominent class of microbiota-derived bile acids

    PubMed Central

    Devlin, A. Sloan; Fischbach, Michael A.

    2015-01-01

    The gut bile acid pool is millimolar in concentration, varies widely in composition among individuals, and is linked to metabolic disease and cancer. Although these molecules derive almost exclusively from the microbiota, remarkably little is known about which bacterial species and genes are responsible for their biosynthesis. Here, we report a biosynthetic pathway for the second most abundant class in the gut, iso (3β-hydroxy) bile acids, whose levels exceed 300 µM in some humans and are absent in others. We show, for the first time, that iso bile acids are produced by Ruminococcus gnavus, a far more abundant commensal than previously known producers; and that the iso bile acid pathway detoxifies deoxycholic acid, favoring the growth of the keystone genus Bacteroides. By revealing the biosynthetic genes for an abundant class of bile acids, our work sets the stage for predicting and rationally altering the composition of the bile acid pool. PMID:26192599

  10. Microbial production of amino acids and derived chemicals: synthetic biology approaches to strain development.

    PubMed

    Wendisch, Volker F

    2014-12-01

    Amino acids are produced at the multi-million-ton-scale with fermentative production of l-glutamate and l-lysine alone being estimated to amount to more than five million tons in the year 2013. Metabolic engineering constantly improves productivities of amino acid producing strains, mainly Corynebacterium glutamicum and Escherichia coli strains. Classical mutagenesis and screening have been accelerated by combination with intracellular metabolite sensing. Synthetic biology approaches have allowed access to new carbon sources to realize a flexible feedstock concept. Moreover, new pathways for amino acid production as well as fermentative production of non-native compounds derived from amino acids or their metabolic precursors were developed. These include dipeptides, α,ω-diamines, α,ω-diacids, keto acids, acetylated amino acids and ω-amino acids. PMID:24922334

  11. Effect of the structure of gallic acid and its derivatives on their interaction with plant ferritin.

    PubMed

    Wang, Qunqun; Zhou, Kai; Ning, Yong; Zhao, Guanghua

    2016-12-15

    Gallic acid and its derivatives co-exist with protein components in foodstuffs, but there is few report on their interaction with proteins. On the other hand, plant ferritin represents not only a novel class of iron supplement, but also a new nanocarrier for encapsulation of bioactive nutrients. However, plant ferritin is easy to be degraded by pepsin in the stomach, thereby limiting its application. Herein, we investigated the interaction of gallic acid and its derivatives with recombinant soybean seed H-2 ferritin (rH-2). We found that these phenolic acids interacted with rH-2 in a structure-dependent manner; namely, gallic acid (GA), methyl gallate (MEGA) and propyl gallate (PG) having three HO groups can bind to rH-2, while their analogues with two HO groups cannot. Consequently, such binding largely inhibited ferritin degradation by pepsin. These findings advance our understanding of the relationship between the structure and function of phenolic acids.

  12. Discovery of a novel activator of 5-lipoxygenase from an anacardic acid derived compound collection

    PubMed Central

    Wisastra, Rosalina; Kok, Petra A.M; Eleftheriadis, Nikolaos; Baumgartner, Matthew P.; Camacho, Carlos J.; Haisma, Hidde J.; Dekker, Frank J.

    2013-01-01

    Lipoxygenases (LOXs) and cyclooxygenases (COXs) metabolize poly-unsaturated fatty acids into inflammatory signaling molecules. Modulation of the activity of these enzymes may provide new approaches for therapy of inflammatory diseases. In this study, we screened novel anacardic acid derivatives as modulators of human 5-LOX and COX-2 activity. Interestingly, a novel salicylate derivative 23a was identified as a surprisingly potent activator of human 5-LOX. This compound showed both non-competitive activation towards the human 5-LOX activator adenosine triphosphate (ATP) and non-essential mixed type activation against the substrate linoleic acid, while having no effect on the conversion of the substrate arachidonic acid. The kinetic analysis demonstrated a non-essential activation of the linoleic acid conversion with a KA of 8.65 μM, αKA of 0.38 μM and a β value of 1.76. It is also of interest that a comparable derivative 23d showed a mixed type inhibition for linoleic acid conversion. These observations indicate the presence of an allosteric binding site in human 5-LOX distinct from the ATP binding site. The activatory and inhibitory behavior of 23a and 23d on the conversion of linoleic compared to arachidonic acid are rationalized by docking studies, which suggest that the activator 23a stabilizes linoleic acid, whereas the larger inhibitor 23d blocks the enzyme active site. PMID:24231650

  13. Bioconversion of volatile fatty acids derived from waste activated sludge into lipids by Cryptococcus curvatus.

    PubMed

    Liu, Jia; Liu, Jia-Nan; Yuan, Ming; Shen, Zi-Heng; Peng, Kai-Ming; Lu, Li-Jun; Huang, Xiang-Feng

    2016-07-01

    Pure volatile fatty acid (VFA) solution derived from waste activated sludge (WAS) was used to produce microbial lipids as culture medium in this study, which aimed to realize the resource recovery of WAS and provide low-cost feedstock for biodiesel production simultaneously. Cryptococcus curvatus was selected among three oleaginous yeast to produce lipids with VFAs derived from WAS. In batch cultivation, lipid contents increased from 10.2% to 16.8% when carbon to nitrogen ratio increased from about 3.5 to 165 after removal of ammonia nitrogen by struvite precipitation. The lipid content further increased to 39.6% and the biomass increased from 1.56g/L to 4.53g/L after cultivation for five cycles using sequencing batch culture (SBC) strategy. The lipids produced from WAS-derived VFA solution contained nearly 50% of monounsaturated fatty acids, including palmitic acid, heptadecanoic acid, ginkgolic acid, stearic acid, oleic acid, and linoleic acid, which showed the adequacy of biodiesel production. PMID:27038264

  14. Docosapentaenoic acid derived metabolites and mediators - The new world of lipid mediator medicine in a nutshell.

    PubMed

    Weylandt, Karsten-H

    2016-08-15

    Recent years have seen the description and elucidation of a new class of anti-inflammatory and pro-resolving lipid mediators. The arachidonic acid (AA)-derived compounds in this class are called lipoxins and have been described in great detail since their discovery thirty years ago. The new players are mediators derived from fish oil omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), called resolvins, protectins and maresins. Taken together, these mediators are also called specialized pro-resolution mediators (SPMs). As compared to the AA/EPA/DHA-derived compounds, research regarding mediators formed from the n-3 and n-6 docosapentaenoic acids (DPAn-3 and DPAn-6) is sparse. However, mono- di- and trihydroxy derivates of the DPAs have anti-inflammatory properties as well, even though mechanisms of their anti-inflammatory action have not been fully elucidated. This review aims to summarize current knowledge regarding the DPA-derived SPMs and their actions. PMID:26546723

  15. Biotechnological production of caffeic acid derivatives from cell and organ cultures of Echinacea species.

    PubMed

    Murthy, Hosakatte Niranjana; Kim, Yun-Soo; Park, So-Young; Paek, Kee-Yoeup

    2014-09-01

    Caffeic acid derivatives (CADs) are a group of bioactive compounds which are produced in Echinacea species especially Echinacea purpurea, Echinacea angustifolia, and Echinacea pallida. Echinacea is a popular herbal medicine used in the treatment of common cold and it is also a prominent dietary supplement used throughout the world. Caffeic acid, chlorogenic acid (5-O-caffeoylquinic acid), caftaric acid (2-O-caffeoyltartaric acid), cichoric acid (2, 3-O-dicaffeoyltartaric acid), cynarin, and echinacoside are some of the important CADs which have varied pharmacological activities. The concentrations of these bioactive compounds are species specific and also they vary considerably with the cultivated Echinacea species due to geographical location, stage of development, time of harvest, and growth conditions. Due to these reasons, plant cell and organ cultures have become attractive alternative for the production of biomass and caffeic acid derivatives. Adventitious and hairy roots have been induced in E. pupurea and E. angustifolia, and suspension cultures have been established from flask to bioreactor scale for the production of biomass and CADs. Tremendous progress has been made in this area; various bioprocess methods and strategies have been developed for constant high-quality productivity of biomass and secondary products. This review is aimed to discuss biotechnological methods and approaches employed for the sustainable production of CADs.

  16. Theophylline-7-acetic acid derivatives with amino acids as anti-tuberculosis agents.

    PubMed

    Voynikov, Yulian; Valcheva, Violeta; Momekov, Georgi; Peikov, Plamen; Stavrakov, Georgi

    2014-07-15

    A series of amides were synthesized by condensation of theophylline-7-acetic acid and eight commercially available amino acid methyl ester hydrochlorides. Consecutive hydrolysis of six of the amido-esters resulted in the formation of corresponding amido-acids. The newly synthesized compounds were evaluated for their in vitro activity against Mycobacterium tuberculosis H37Rv. The activity varied depending on the amino acid fragments and in seven cases exerted excellent values with MICs 0.46-0.26 μM. Assessment of the cytotoxicity revealed that the compounds were not cytotoxic against the human embryonal kidney cell line HEK-293T. The theophylline-7-acetamides containing amino acid moieties appear to be promising lead compounds for the development of antimycobacterial agents.

  17. Synthesis of conjugated linoleic acid by the linoleate isomerase complex in food-derived lactobacilli

    PubMed Central

    Yang, B.; Chen, H.; Gu, Z.; Tian, F.; Ross, R. P.; Stanton, C.; Chen, Y. Q.; Chen, W.; Zhang, H.

    2015-01-01

    Aims To assess strains of lactobacilli for their capacity to produce functional fatty acid-conjugated linoleic acid. To assess the linoleate isomerase for CLA production in the most efficient CLA producer. Methods and Results In this study, strains of food-derived lactobacilli were cultured in media with linoleic acid and CLA production was assessed. Most of the selected strains produced CLA at different levels, with Lactobacillus plantarum ZS2058 being the most efficient CLA producer converting over 50% of linoleic acid to c9, t11-CLA and t9, t11-CLA. Some intermediates 10-hydroxy-cis-12-octadecenoic acid, 10-oxo-cis-12-octadecenoic acid and 10-oxo-trans-11-octadecenoic acid were determined via GC-MS. The genes coding the multicomponent linoleate isomerase containing myosin-cross-reactive antigen, short-chain dehydrogenase/oxidoreductase and acetoacetate decarboxylase for CLA production in Lact. plantarum ZS2058 were cloned and expressed in Escherichia coli. With the mixture of recombinant E. coli, c9, t11-CLA and three kinds of intermediates were produced from linoleic acid, which were in line with those in the lactobacilli. Conclusions The ability for CLA production by lactobacilli exhibited variation. Lactobacillus plantarum and Lact. bulgaricus were the most efficient producers in the selected strains. Lact. plantarum ZS2058 converted linoleic acid to CLAs with 10-hydroxy-cis-12-octadecenoic acid, 10-oxo-cis-12-octadecenoic acid and 10-oxo-trans-11-octadecenoic acid as intermediates. The multiple-step reactions for CLA production catalysed by multicomponent linoleate isomerase in Lact. plantarum ZS2058 were confirmed successfully. Significance and Impact of the study Multicomponent linoleate isomerase provides important results for the illustration of the mechanism for CLA production in lactic acid bacteria. Food-derived lactobacilli with CLA production ability offers novel opportunities for functional foods development. PMID:24750362

  18. Induction of hepatocyte growth factor production in human dermal fibroblasts by caffeic acid derivatives.

    PubMed

    Kurisu, Manami; Nakasone, Rie; Miyamae, Yusaku; Matsuura, Daisuke; Kanatani, Hirotoshi; Yano, Shingo; Shigemori, Hideyuki

    2013-01-01

    Hepatocyte growth factor (HGF) has mitogenic, motogenic, and morphogenic activities in epithelial cells. Induction of HGF production may be involved in organ regeneration, wound healing and embryogenesis. In this study, we examined the effects of caffeic acid derivatives including 4,5-di-O-caffeoylquinic acid (1) and acteoside (2) on HGF production in Neonatal Normal Human Dermal Fibroblasts (NHDF). Both 4,5-di-O-caffeoylquinic acid (1) and acteoside (2) significantly induced HGF production dose-dependent manner. To know the important substructure for HGF production activity, we next investigated the effect of the partial structure of these caffeic acid derivatives. From the results, caffeic acid (3) showed strong activity on the promotion of HGF production, while hydroxytyrosol (4) and quinic acid (5) didn't show any activity. Our findings suggest that the caffeoyl moiety of caffeic acid derivatives is essential for accelerated production of HGF. The compound which has the caffeoyl moiety may be useful for the treatment of some intractable organ disease.

  19. Neuraminidase inhibition of Dietary chlorogenic acids and derivatives - potential antivirals from dietary sources.

    PubMed

    Gamaleldin Elsadig Karar, Mohamed; Matei, Marius-Febi; Jaiswal, Rakesh; Illenberger, Susanne; Kuhnert, Nikolai

    2016-04-01

    Plants rich in chlorogenic acids (CGAs), caffeic acids and their derivatives have been found to exert antiviral effects against influenza virus neuroaminidase. In this study several dietary naturally occurring chlorogenic acids, phenolic acids and derivatives were screened for their inhibitory activity against neuroaminidases (NAs) from C. perfringens, H5N1 and recombinant H5N1 (N-His)-Tag using a fluorometric assay. There was no significant difference in inhibition between the different NA enzymes. The enzyme inhibition results indicated that chlorogenic acids and selected derivatives, exhibited high activities against NAs. It seems that the catechol group from caffeic acid was important for the activity. Dietary CGA therefore show promise as potential antiviral agents. However, caffeoyl quinic acids show low bioavailibility and are intensly metabolized by the gut micro flora, only low nM concentrations are observed in plasma and urine, therefore a systemic antiviral effect of these compounds is unlikely. Nevertheless, gut floral metabolites with a catechol moiety or structurally related dietary phenolics with a catechol moiety might serve as interesting compounds for future investigations. PMID:27010419

  20. Ionic derivatives of betulinic acid as novel HIV-1 protease inhibitors.

    PubMed

    Zhao, Hua; Holmes, Shaletha S; Baker, Gary A; Challa, Suresh; Bose, Himangshu S; Song, Zhiyan

    2012-10-01

    Betulinic acid is a natural product possessing abundant and favourable biological activity, including anti-cancer, anti-malarial, anti-inflammatory and anti-HIV properties, while causing minimal toxicity to unaffected cells. The full biological potency of betulinic acid cannot be fully unlocked, however, for a number of reasons, a primary one being its limited solubility in aqueous and biologically pertinent organic media. Aiming to improve the water solubility of betulinic acid without disrupting its structurally related bioactivity, we have prepared different ionic derivatives of betulinic acid. Inhibition bioassays on HIV-1 protease-catalysed peptide hydrolysis indicate significantly improved performance resulting from converting the betulinic acid to organic salt form. Indeed, for one particular cholinium-based derivative, its water solubility is improved more than 100 times and the half maximal inhibitory concentration (IC(50)) value (22 μg mL(-1)) was one-third that of wide-type betulinic acid (60 μg mL(-1)). These encouraging results advise that additional studies of ionic betulinic acid derivatives as a therapeutic solution against HIV-1 infection are warranted.

  1. Lanthanum(III) and praseodymium(III) derivatives with dithiocarbamates derived from α-amino acids

    NASA Astrophysics Data System (ADS)

    Rai, Anita; Sengupta, Soumitra K.; Pandey, Om P.

    2006-06-01

    Lanthanum(III) and praseodymium(III) complexes with dithiocarbamates have been synthesized by the reactions of lanthanum(III) and praseodymium(III) chloride with barium dithiocarbamate and complexes of type [LnCl(L)H 2O] n have been obtained (where Ln = La(III) or Pr(III); L = barium salt of dithiocarbamate derived from glycine, L-leucine, L-valine, DL-alanine). The complexes have been characterized by elemental analysis, molar conductance, electronic absorption and fluorescence, infrared, far infrared, 1H NMR spectral studies. The presence of coordinated water molecule is inferred from thermogravimetric analysis which indicates the loss of one water molecule at 150-170 °C. The oscillator strength, Judd-Ofelt intensity parameter, stimulated emission cross-section, etc. have been obtained for different transitions of Pr 3+.

  2. Lanthanum(III) and praseodymium(III) derivatives with dithiocarbamates derived from alpha-amino acids.

    PubMed

    Rai, Anita; Sengupta, Soumitra K; Pandey, Om P

    2006-06-01

    Lanthanum(III) and praseodymium(III) complexes with dithiocarbamates have been synthesized by the reactions of lanthanum(III) and praseodymium(III) chloride with barium dithiocarbamate and complexes of type [LnCl(L)H2O]n have been obtained (where Ln=La(III) or Pr(III); L=barium salt of dithiocarbamate derived from glycine, L-leucine, L-valine, DL-alanine). The complexes have been characterized by elemental analysis, molar conductance, electronic absorption and fluorescence, infrared, far infrared, 1H NMR spectral studies. The presence of coordinated water molecule is inferred from thermogravimetric analysis which indicates the loss of one water molecule at 150-170 degrees C. The oscillator strength, Judd-Ofelt intensity parameter, stimulated emission cross-section, etc. have been obtained for different transitions of Pr3+.

  3. The retinoic acid derivative Ro 11-1430 in Acne vulgaris. A controlled multicenter trial against retinoic acid.

    PubMed

    Christiansen, J; Holm, P; Reymann, F

    1977-01-01

    In a double-blind controlled multicenter trial consisting of 257 patients with acne vulgaris an 8-week topical treatment with the retinoic acid derivative Ro 11-1430 (0.1% lotion) was compared with vitamin A acid (0.05% lotion) and the lotion alone (placebo). In reducing the number of comedones vitamin A acid was superior to Ro 11-1430, which was significantly better than placebo. The reduction in number of papules and pustules was not statistically significant on either treatment. Local side effects, i.e. erythema, desquamation, burning and pruritus occurred more frequently and were more severe on vitamin A acid than on Ro 11-1430 and placebo which did not differ. No correlation was found between incidence and severity of local reactions and therapeutic effect.

  4. An elementary derivation of the hard/soft-acid/base principle.

    PubMed

    Ayers, Paul W

    2005-04-01

    The hard/soft-acid/base (HSAB) principle indicates that hard acids prefer binding to hard bases (often forming bonds with substantial ionic character) while soft acids prefer binding to soft bases (often forming bonds with substantial covalent character). Though the HSAB principle is a foundational concept of the modern theory of acids and bases, the theoretical underpinnings of the HSAB principle remain murky. This paper examines the exchange reaction, wherein two molecules, one the product of reacting a hard acid and a soft base and the other the product of reacting a soft acid with a hard base, exchange substituents to form the preferred hard-hard and soft-soft product. A simple derivation shows that this reaction is exothermic, proving the validity of the HSAB principle. The analysis leads to the simple and conceptually appealing conclusion that the HSAB principle is a driven by simple electron transfer effects.

  5. Catabolism of phenylpropionic acid and its 3-hydroxy derivative by Escherichia coli.

    PubMed Central

    Burlingame, R; Chapman, P J

    1983-01-01

    A number of laboratory strains and clinical isolates of Escherichia coli utilized several aromatic acids as sole sources of carbon for growth. E. coli K-12 used separate reactions to convert 3-phenylpropionic and 3-(3-hydroxyphenyl)propionic acids into 3-(2,3-dihydroxyphenyl)propionic acid which, after meta-fission of the benzene nucleus, gave succinate, pyruvate, and acetaldehyde as products. Enzyme assays and respirometry showed that all enzymes of this branched pathway were inducible and that syntheses of enzymes required to convert the two initial growth substrates into 3-(2,3-dihydroxyphenyl)propionate are under separate control. E. coli K-12 also grew with 3-hydroxycinnamic acid as sole source of carbon; the ability of cells to oxidize cinnamic and 3-phenylpropionic acids, and hydroxylated derivatives, was investigated. The lactone of 4-hydroxy-2-ketovaleric acid was isolated from enzymatic reaction mixtures and its properties, including optical activity, were recorded. PMID:6345502

  6. A Molecular Necklace: Threading β-Cyclodextrins onto Polymers Derived from Bile Acids.

    PubMed

    Jia, Yong-Guang; Malveau, Cedric; Mezour, Mohamed A; Perepichka, Dmitrii F; Zhu, X X

    2016-09-19

    A molecular necklace of polypseudorotaxanes was prepared by threading β-cyclodextrins (β-CD) onto biodegradable and thermoresponsive polyurethanes derived from bile acids. These polyurethanes were synthesized via a simple step condensation of bile acid-based dicarbonate with poly(ethylene glycol)-diamine. The β-CD rings slide onto the poly(ethylene glycol) segments and selectively recognize the bile acid units of the polyurethane chains, whereas the poly(ethylene glycol) segments remain crystalline with a lower crystallinity. This bio-compound-derived molecular necklace can be visualized by scanning tunneling microscopy. The polypseudorotaxanes show thermosensitivity in water and the phase transition temperature may be fine-tuned by varying the molar ratios of β-CD to the bile acid units. Such an interesting necklace model of polypseudorotaxane constructed from natural compounds may lead to the further exploration of their applications, such as as an enzyme model, due to their biological nature. PMID:27558980

  7. A Molecular Necklace: Threading β-Cyclodextrins onto Polymers Derived from Bile Acids.

    PubMed

    Jia, Yong-Guang; Malveau, Cedric; Mezour, Mohamed A; Perepichka, Dmitrii F; Zhu, X X

    2016-09-19

    A molecular necklace of polypseudorotaxanes was prepared by threading β-cyclodextrins (β-CD) onto biodegradable and thermoresponsive polyurethanes derived from bile acids. These polyurethanes were synthesized via a simple step condensation of bile acid-based dicarbonate with poly(ethylene glycol)-diamine. The β-CD rings slide onto the poly(ethylene glycol) segments and selectively recognize the bile acid units of the polyurethane chains, whereas the poly(ethylene glycol) segments remain crystalline with a lower crystallinity. This bio-compound-derived molecular necklace can be visualized by scanning tunneling microscopy. The polypseudorotaxanes show thermosensitivity in water and the phase transition temperature may be fine-tuned by varying the molar ratios of β-CD to the bile acid units. Such an interesting necklace model of polypseudorotaxane constructed from natural compounds may lead to the further exploration of their applications, such as as an enzyme model, due to their biological nature.

  8. Comparative analysis of the anxiolytic effects of 3-hydroxypyridine and succinic acid derivatives.

    PubMed

    Volchegorskii, I A; Miroshnichenko, I Yu; Rassokhina, L M; Faizullin, R M; Malkin, M P; Pryakhina, K E; Kalugina, A V

    2015-04-01

    Threefold administration of 3-hydroxypyridine derivatives emoxipine and mexidol in optimal doses corresponding to the therapeutic dose range for humans produced an anxiolytic effect and stimulated risk behavior in the elevated plus maze test in rats. These effects were most pronounced after injection of 3-hydroxypyridine derivative emoxipine. Combination of 3-hydroxypyridine cation and succinate anion in the mexidol structure led to attenuation of the anxiolytic effect and less pronounced stimulation of the risk behavior. By the anxiolytic effect and induction of risk behavior, emoxipine and mexidol were close to the reference substance amitriptyline. Reamberin, a succinic acid derivative, had no pronounced tranquilizing properties, but risk behavior induction was similar to that produced by mexidol. In contrast to other test agents, the reference substance α-lipoic acid produced anxiogenic effects and suppressed risk behavior. The obtained results suggest that Russian-made 3-hydroxypyridine derivatives emoxipine and mexidol are promising preparations for the treatment of anxiety disorders. PMID:25894772

  9. Nitrogenous compounds stimulate glucose-derived acid production by oral Streptococcus and Actinomyces.

    PubMed

    Norimatsu, Yuka; Kawashima, Junko; Takano-Yamamoto, Teruko; Takahashi, Nobuhiro

    2015-09-01

    Both Streptococcus and Actinomyces can produce acids from dietary sugars and are frequently found in caries lesions. In the oral cavity, nitrogenous compounds, such as peptides and amino acids, are provided continuously by saliva and crevicular gingival fluid. Given that these bacteria can also utilize nitrogen compounds for their growth, it was hypothesized that nitrogenous compounds may influence their acid production; however, no previous studies have examined this topic. Therefore, the present study aimed to assess the effects of nitrogenous compounds (tryptone and glutamate) on glucose-derived acid production by Streptococcus and Actinomyces. Acid production was evaluated using a pH-stat method under anaerobic conditions, whereas the amounts of metabolic end-products were quantified using high performance liquid chromatography. Tryptone enhanced glucose-derived acid production by up to 2.68-fold, whereas glutamate enhanced Streptococcus species only. However, neither tryptone nor glutamate altered the end-product profiles, indicating that the nitrogenous compounds stimulate the whole metabolic pathways involving in acid production from glucose, but are not actively metabolized, nor do they alter metabolic pathways. These results suggest that nitrogenous compounds in the oral cavity promote acid production by Streptococcus and Actinomyces in vivo.

  10. In vitro effects of cinnamic acid derivatives on protein tyrosine phosphatase 1B.

    PubMed

    Adisakwattana, Sirichai; Pongsuwan, Jirawan; Wungcharoen, Chompunut; Yibchok-anun, Sirintorn

    2013-10-01

    Protein Tyrosine Phosphatase 1B (PTP1B) is a major negative regulator of insulin signaling pathways. Finding selective PTP1B inhibitors from natural sources has been widely recognized as a potential drug target for the treatment of diabetes mellitus and obesity. In the present study, we evaluated the inhibitory activity of cinnamic acid derivatives against PTP1B in vitro. Among 14 cinnamic acid derivatives and related compounds, the most potent inhibitor PTP1Bs were o-hydroxycinnamic acid and p-hydroxycinnamic acid, which had IC50 values of 137.67 ± 13.37 and 181.60 ± 9.34 µM, respectively. The kinetics analysis revealed that PTP1B was inhibited by o-hydroxycinnamic acid and p-hydroxycinnamic acid in a non-competitive manner. o-Hydroxycinnamic acid (25 μM) and p-hydroxycinnamic acid (25 μM), in combination with sodium orthovanadate (0.0125 μM), demonstrated a synergistic effect to inhibit PTP1B activity. In conclusion, the findings provide a new insight into naturally occurring PTP1B inhibitors that could be useful for treatment of diabetes and obesity.

  11. Solvent-free lipase-catalyzed synthesis of a novel hydroxyl-fatty acid derivative of kojic acid.

    PubMed

    El-Boulifi, Noureddin; Ashari, Siti Efliza; Serrano, Marta; Aracil, Jose; Martínez, Mercedes

    2014-02-01

    The aim of this work was the synthesis of a novel hydroxyl-fatty acid derivative of kojic acid rich in kojic acid monoricinoleate (KMR) which can be widely used in the cosmetic and food industry. The synthesis of KMR was carried out by lipase-catalysed esterification of ricinoleic and kojic acids in solvent-free system. Three immobilized lipases were tested and the best KMR yields were attained with Lipozyme TL IM and Novozym 435. Since Lipozyme TL IM is the cheapest, it was selected to optimize the reaction conditions. The optimal reaction conditions were 80 °C for the temperature, 1:1 for the alcohol/acid molar ratio, 600 rpm for stirring speed and 7.8% for the catalyst concentration. Under these conditions, the reaction was scaled up in a 5×10⁻³ m³ stirred tank reactor. ¹H-¹³C HMBC-NMR showed that the primary hydroxyl group of kojic acid was regioselectively esterified. The KMR has more lipophilicity than kojic acid and showed antioxidant activity that improves the oxidation stability of biodiesel.

  12. Technological and economic potential of poly(lactic acid) and lactic acid derivatives

    SciTech Connect

    Datta, R.; Tsai, S.P.; Bonsignore, P.; Moon, S.H.; Frank, J.R.

    1993-10-01

    Lactic acid has been an intermediate-volume specialty chemical (world production {approximately}40,000 tons/yr) used in a wide range of food processing and industrial applications. lactic acid h,as the potential of becoming a very large volume, commodity-chemical intermediate produced from renewable carbohydrates for use as feedstocks for biodegradable polymers, oxygenated chemicals, plant growth regulators, environmentally friendly ``green`` solvents, and specially chemical intermediates. In the past, efficient and economical technologies for the recovery and purification of lactic acid from crude fermentation broths and the conversion of tactic acid to the chemical or polymer intermediates had been the key technology impediments and main process cost centers. The development and deployment of novel separations technologies, such as electrodialysis (ED) with bipolar membranes, extractive distillations integrated with fermentation, and chemical conversion, can enable low-cost production with continuous processes in large-scale operations. The use of bipolar ED can virtually eliminate the salt or gypsum waste produced in the current lactic acid processes. In this paper, the recent technical advances in tactic and polylactic acid processes are discussed. The economic potential and manufacturing cost estimates of several products and process options are presented. The technical accomplishments at Argonne National Laboratory (ANL) and the future directions of this program at ANL are discussed.

  13. Synthesis of amino-acid derivatives and dipeptides with an original peptidase enzyme.

    PubMed

    Auriol, D; Paul, F; Yoshpe, I; Gripon, J C; Monsan, P

    1991-01-01

    A peptidase from the non pathogenic Staphylococcus sp. strain BEC 299 was purified to a final specific activity of 84,400 U/mg protein. Its molecular weight is 450 kDa and optimum pH 10.0. This enzyme catalyzes the synthesis of dipeptides (aspartame) and alpha-amino acid derivatives (N-L-malyl-L-tyrosine ethyl ester). The influence of cosolvents and pH on dipeptides and alpha-amino acid derivative synthesis is described. Finally, we detail the use of the peptidase as a reagent in protease-catalyzed peptide synthesis.

  14. Cinnamic acid derivatives induce cell cycle arrest in carcinoma cell lines.

    PubMed

    Sova, Matej; Žižak, Željko; Stanković, Jelena A Antic; Prijatelj, Matevž; Turk, Samo; Juranić, Zorica D; Mlinarič-Raščan, Irena; Gobec, Stanislav

    2013-08-01

    Cinnamic acid derivatives can be found in plant material, and they possess a remarkable variety of biological effects. In the present study, we have investigated the cytotoxic effects of representative cinnamic acid esters and amides. The cytotoxicity was determined by MTT test on human cervix adenocarcinoma (HeLa), myelogenous leukemia (K562), malignant melanoma (Fem-x), and estrogen-receptor-positive breast cancer (MCF-7) cells, versus peripheral blood mononuclear cells (PBMCs) without or with the addition of the plant lectin phytohemaglutinin (PHA). The compounds tested showed significant cytotoxicity (IC50s between 42 and 166 µM) and furthermore selectivity of these cytotoxic effects on the malignant cell lines versus the PBMCs was also seen, especially when electron-withdrawing groups, such as a cyano group (compound 5), were present on the aromatic rings of the alcohol or amine parts of the cinnamic acid derivatives. The additional study on cell cycle phase distribution indicated that novel cinnamic acid derivatives inhibit cell growth by induction of cell death. Thus, cinnamic acids derivatives represent important lead compounds for further development of antineoplastic agents.

  15. Promise of Retinoic Acid-Triazolyl Derivatives in Promoting Differentiation of Neuroblastoma Cells.

    PubMed

    Lone, Ali Mohd; Dar, Nawab John; Hamid, Abid; Shah, Wajaht Amin; Ahmad, Muzamil; Bhat, Bilal A

    2016-01-20

    Retinoic acid induces differentiation in various types of cells including skeletal myoblasts and neuroblasts and maintains differentiation of epithelial cells. The present study demonstrates synthesis and screening of a library of retinoic acid-triazolyl derivatives for their differentiation potential on neuroblastoma cells. Click chemistry approach using copper(I)-catalyzed azide-alkyne cycloaddition was adopted for the preparation of these derivatives. The neurite outgrowth promoting potential of retinoic acid-triazolyl derivatives was studied on neuroblastoma cells. Morphological examination revealed that compounds 8a, 8e, 8f, and 8k, among the various derivatives screened, exhibited promising neurite-outgrowth inducing activity at a concentration of 10 μM compared to undifferentiated and retinoic acid treated cells. Further on, to confirm this differentiation potential of these compounds, neuroblastoma cells were probed for expression of neuronal markers such as NF-H and NeuN. The results revealed a marked increase in the NF-H and NeuN protein expression when treated with 8a, 8e, 8f, and 8k compared to undifferentiated and retinoic acid treated cells. Thus, these compounds could act as potential leads in inducing neuronal differentiation for future studies.

  16. Development, characterization and commercial application of palm based dihydroxystearic acid and its derivatives: an overview.

    PubMed

    Koay, Gregory F L; Chuah, Teong-Guan; Zainal-Abidin, Sumaiya; Ahmad, Salmiah; Choong, Thomas S Y

    2011-01-01

    Hydroxyl fatty acids and their derivatives are of high value due to their wide range of industrial application, including cosmetic, food, personal care and pharmaceutical products. Realizing the importance of hydroxyl fatty acids, and yet due to the absence of the conventional starting raw materials, Malaysia has developed 9,10-dihydroxystearic acid (9,10-DHSA) and its derivatives from locally abundant palm based oils. The aim of this article is to provide a general description of the works that have thus far being done on palm based 9,10-DHSA: starting from its conception and production from commercial grade palm based crude oleic acid via epoxidation and hydrolysis, purification through solvent crystallization and characterization through wet and analytical chemistry, moving on to developmental works done on producing its derivatives through blending, esterification, amidation and polymerization, and completing with applications of 9,10-DHSA and its derivatives, e.g. DHSA-stearates and DHSA-estolides, in commercial products such as soaps, deodorant sticks and shampoos. This article incorporates some of the patent filed technological knowhow on 9,10-DHSA and its derivatives, and will also point out some of the shortcomings in previously published documents and provide some recommendations for future research works in mitigating these shortcomings.

  17. Additive-free decarboxylative coupling of cinnamic acid derivatives in water: synthesis of allyl amines.

    PubMed

    Park, Kyungho; Lee, Sunwoo

    2015-03-01

    The first example of an additive-free decarboxylative coupling of cinnamic acid derivatives with formaldehyde and amines to afford the corresponding allyl amines is reported. This reaction is highly environmentally friendly because it was conducted in H2O and without any additives, releasing only CO2 and H2O as byproducts. This reaction showed a broad substrate scope including cyclic and acyclic amines and high functional group tolerance. Moreover, phenyl dienoic acid participated in this type of decarboxylative coupling reaction.

  18. Antimicrobial screening and quantitative determination of benzoic acid derivative of Gomphrena celosioides by TLC-densitometry.

    PubMed

    de Moura, Rute Mendonça Xavier; Pereira, Paulo Sérgio; Januário, Ana Helena; França, Suzelei de Castro; Dias, Diones Aparecida

    2004-11-01

    The antimicrobial activity of ethanolic extract and pure compounds of Gomphrena celosioides have been screened by Kirby-Bauer method. Quantitative determination of 4-hydroxy-3-methoxy-benzoic acid in stems, leaves, flowers and roots was established by TLC-densitometry. Results showed significant activity against Staphylococcus aureus and Salmonella typhi. There were no significant differences in the determined benzoic acid derivative. PMID:15516759

  19. Paecilonic acids A and B, bicyclic fatty acids from the jellyfish-derived fungus Paecilomyces variotii J08NF-1.

    PubMed

    Wang, Haibo; Hong, Jongki; Yin, Jun; Liu, Juan; Liu, Yonghong; Choi, Jae Sue; Jung, Jee H

    2016-05-01

    Two new bicyclic fatty acids, paecilonic acids A and B (1 and 2), were isolated from the culture broth of the marine fungus Paecilomyces variotii derived from the jellyfish Nemopilema nomurai. Compounds 1 and 2 share the same molecular formula and possess a 6,8-dioxabicyclo[3.2.1]octane core skeleton. The planar structures of compounds 1 and 2 were established by spectroscopic analysis, which included NMR and ESI-MS/MS. Relative and absolute configurations were determined by analyzing coupling constants, NOESY correlations, and optical rotations. PMID:27009897

  20. Paecilonic acids A and B, bicyclic fatty acids from the jellyfish-derived fungus Paecilomyces variotii J08NF-1.

    PubMed

    Wang, Haibo; Hong, Jongki; Yin, Jun; Liu, Juan; Liu, Yonghong; Choi, Jae Sue; Jung, Jee H

    2016-05-01

    Two new bicyclic fatty acids, paecilonic acids A and B (1 and 2), were isolated from the culture broth of the marine fungus Paecilomyces variotii derived from the jellyfish Nemopilema nomurai. Compounds 1 and 2 share the same molecular formula and possess a 6,8-dioxabicyclo[3.2.1]octane core skeleton. The planar structures of compounds 1 and 2 were established by spectroscopic analysis, which included NMR and ESI-MS/MS. Relative and absolute configurations were determined by analyzing coupling constants, NOESY correlations, and optical rotations.

  1. Water extract of propolis and its main constituents, caffeoylquinic acid derivatives, exert neuroprotective effects via antioxidant actions.

    PubMed

    Nakajima, Yoshimi; Shimazawa, Masamitsu; Mishima, Satoshi; Hara, Hideaki

    2007-01-01

    We investigated whether water extract of Brazilian green propolis (WEP) and its main constituents [caffeoylquinic acid derivatives (3,4-di-O-caffeoylquinic acid, 3,5-di-O-caffeoylquinic acid, chlorogenic acid) and cinnamic acid derivatives (p-coumaric acid, artepillin C, drupanin, baccharin)] exert neuroprotective effects against the retinal damage induced by oxidative stress. Additionally, their neuroprotective effects were compared with their antioxidant effects. WEP, 3,4-di-O-caffeoylquinic acid, 3,5-di-O-caffeoylquinic acid, chlorogenic acid, and p-coumaric acid (but not artepillin C, baccharin, or drupanin) concentration-dependently inhibited oxidative stress-induced neurotoxicity [achieved using L-buthionine-(S,R)-sulfoximine (BSO) to deplete glutathione in combination with glutamate to inhibit cystine uptake] in cultured retinal ganglion cells (RGC-5, a rat ganglion cell line transformed using E1A virus). At their effective concentrations against oxidative stress-induced retinal damage, WEP, 3,4-di-caffeoylquinic acid, 3,5-di-caffeoylquinic acid, and chlorogenic acid (but not cinnamic acid derivatives) inhibited lipid peroxidation (LPO) in mouse forebrain homogenates. Thus, the neuroprotective effects of WEP and caffeoylquinic acid derivatives paralleled those against LPO. These findings indicate that WEP and caffeoylquinic acid derivatives have neuroprotective effects against retinal damage in vitro, and that these effects may be partly mediated via antioxidant effects.

  2. A Direct, Biomass-Based Synthesis of Benzoic Acid: Formic Acid-Mediated Deoxygenation of the Glucose-Derived Materials Quinic Acid and Shikimic Acid

    SciTech Connect

    Arceo, Elena; Ellman, Jonathan; Bergman, Robert

    2010-05-03

    An alternative biomass-based route to benzoic acid from the renewable starting materials quinic acid and shikimic acid is described. Benzoic acid is obtained selectively using a highly efficient, one-step formic acid-mediated deoxygenation method.

  3. Syntheses of biodiesel precursors: sulfonic acid catalysts for condensation of biomass-derived platform molecules.

    PubMed

    Balakrishnan, Madhesan; Sacia, Eric R; Bell, Alexis T

    2014-04-01

    Synthesis of transportation fuel from lignocellulosic biomass is an attractive solution to the green alternative-energy problem. The production of biodiesel, in particular, involves the process of upgrading biomass-derived small molecules to diesel precursors containing a specific carbon range (C11 -C23). Herein, a carbon-upgrading process utilizing an acid-catalyzed condensation of furanic platform molecules from biomass is described. Various types of sulfonic acid catalysts have been evaluated for this process, including biphasic and solid supported catalysts. A silica-bound alkyl sulfonic acid catalyst has been developed for promoting carbon-carbon bond formation of biomass-derived carbonyl compounds with 2-methylfuran. This hydrophobic solid acid catalyst exhibits activity and selectivity that are comparable to those of a soluble acid catalyst. The catalyst can be readily recovered and recycled, possesses appreciable hydrolytic stability in the presence of water, and retains its acidity over multiple reaction cycles. Application of this catalyst to biomass-derived platform molecules led to the synthesis of a variety of furanic compounds, which are potential biodiesel precursors.

  4. Structural and spectroscopic investigation on a new potentially bioactive di-hydrazone containing thiophene heterocyclic rings

    NASA Astrophysics Data System (ADS)

    Nogueira, Vanessa de S.; Ramalho Freitas, Maria Clara; Cruz, Wellington S.; Ribeiro, Tatiana S.; Resende, Jackson A. L. C.; Rey, Nicolás A.

    2016-02-01

    Hydrazones and several substituted hydrazones are associated with a broad spectrum of biological activities, as well as compounds containing the thiophene ring. In this context, a novel di-hydrazone derived from 2-thiophenecarboxylic acid hydrazide was synthesized and completely characterized by elemental analysis, XRD, FT-IR, Raman and UV-Vis spectroscopies, thermogravimetry, 1H NMR, 1H-1H COSY and 1H-1H ROESY. A preliminary in silico pharmacological evaluation was also performed in order to assess the performance of the new compound regarding some molecular properties relevant for a drug's pharmacokinetics in the human body.

  5. Safety assessment of animal- and plant-derived amino acids as used in cosmetics.

    PubMed

    Burnett, Christina; Heldreth, Bart; Bergfeld, Wilma F; Belsito, Donald V; Hill, Ronald A; Klaassen, Curtis D; Liebler, Daniel C; Marks, James G; Shank, Ronald C; Slaga, Thomas J; Snyder, Paul W; Andersen, F Alan

    2014-01-01

    The Cosmetic Ingredient Review Expert Panel (Panel) reviewed the safety of animal- and plant-derived amino acid mixtures, which function as skin and hair conditioning agents. The safety of α-amino acids as direct food additives has been well established, based on extensive research through acute and chronic dietary exposures and the Panel previously has reviewed the safety of individual α-amino acids in cosmetics. The Panel focused its review on dermal irritation and sensitization data relevant to the use of these ingredients in topical cosmetics. The Panel concluded that these 21 ingredients are safe in the present practices of use and concentration as used in cosmetics.

  6. Nahuoic Acids B-E, Polyhydroxy Polyketides from the Marine-Derived Streptomyces sp. SCSGAA 0027.

    PubMed

    Nong, Xu-Hua; Zhang, Xiao-Yong; Xu, Xin-Ya; Wang, Jie; Qi, Shu-Hua

    2016-01-22

    Four new polyol polyketides containing a decalin ring, nahuoic acids B-E (1-4), together with a known analogue, nahuoic acid A (5), possessing an unprecedented carbon skeleton, were isolated from a culture broth of the marine-derived Streptomyces sp. SCSGAA 0027. Their structures were determined by detailed analysis of spectroscopic data and chemical transformations including acetonide formation and Mosher's ester method. Compounds 1-5 showed weak antibiofilm activity against Shewanella onedensis MR-1 biofilm. This is the first series of analogues of the novel selective SETD8 inhibitor nahuoic acid A. PMID:26684286

  7. Nahuoic Acids B-E, Polyhydroxy Polyketides from the Marine-Derived Streptomyces sp. SCSGAA 0027.

    PubMed

    Nong, Xu-Hua; Zhang, Xiao-Yong; Xu, Xin-Ya; Wang, Jie; Qi, Shu-Hua

    2016-01-22

    Four new polyol polyketides containing a decalin ring, nahuoic acids B-E (1-4), together with a known analogue, nahuoic acid A (5), possessing an unprecedented carbon skeleton, were isolated from a culture broth of the marine-derived Streptomyces sp. SCSGAA 0027. Their structures were determined by detailed analysis of spectroscopic data and chemical transformations including acetonide formation and Mosher's ester method. Compounds 1-5 showed weak antibiofilm activity against Shewanella onedensis MR-1 biofilm. This is the first series of analogues of the novel selective SETD8 inhibitor nahuoic acid A.

  8. Synthesis and biological evaluation of pseudolaric acid B derivatives as potential immunosuppressive agents.

    PubMed

    Chen, Shou-Qiang; Wang, Jie; Zhao, Chuan; Sun, Qiang-Wen; Wang, Yi-Teng; Ai, Ting; Li, Tan; Gao, Ying; Wang, Huo; Chen, Hong

    2015-01-01

    Pseudolaric acid B (PB) derivatives with immunosuppressive activity were found by our group. In order to find potential immunosuppressive agents with high efficacy and low toxicity, a series of novel PB derivatives were synthesized and evaluated on their immunosuppressive activities. Most of the synthesized compounds were tested in vitro on murine T and B proliferation. In particular, compound 11 exhibited excellent inhibitory activity toward murine T cells (up to 19-fold enhancement compared to that of mycophenolatemofetil) and little cytotoxicity toward normal murine spleen cells. These experimental data demonstrated that some of these PB derivatives have great potential for future immunosuppressive studies.

  9. Interactions of cyclic and non-cyclic naphthalene diimide derivatives with different nucleic acids.

    PubMed

    Czerwinska, Izabella; Sato, Shinobu; Juskowiak, Bernard; Takenaka, Shigeori

    2014-05-01

    Recently, strategy based on stabilization of G-quadruplex telomeric DNA by small organic molecule has been realized by naphthalene diimide derivatives (NDIs). At the same time NDIs bind to DNA duplex as threading intercalators. Here we present cyclic derivative of naphthalene diimide (ligand 1) as DNA-binding ligand with ability to recognition of different structures of telomeric G-quadruplexes and ability to bis-intercalate to double-stranded helixes. The results have been compared to non-cyclic derivative (ligand 2) and revealed that preferential binding of ligands to nucleic acids strongly depends on their topology and structural features of ligands. PMID:24726302

  10. Steric hindrance of 2,6-disubstituted benzoic acid derivatives on the uptake via monocarboxylic acid transporters from the apical membranes of Caco-2 cells.

    PubMed

    Tsukagoshi, Kensuke; Kimura, Osamu; Endo, Tetsuya

    2014-05-01

    Benzoic acid is a typical substrate for monocarboxylic acid transporters (MCTs), and easily taken up from the apical membranes of Caco-2 cells by MCTs. However, some benzoic acid derivatives were sparingly taken up by Caco-2 cells. To elucidate the mechanism of lower uptake of the derivatives, we investigated the effect of substitution of benzene ring on the uptake by MCTs using Caco-2 cells. Among the benzoic acid derivatives tested, the uptake of 2,6-disubstituted benzoic acids was markedly lower than that of other benzoic acids. Co-incubation of the 2,6-disubstituted derivatives with benzoic acid did not decrease the uptake of benzoic acid, while co-incubation with other derivatives significantly decreased the uptake of benzoic acid. Kinetic analyses elucidated that the uptake of 2,6-dichlorobenzoic acid and 2,3,6-trichlorobenzoic acid did not involve the carrier-mediated process. The 2,6-disubstitution of benzoic acid may prevent the access of carboxylic acid group to MCTs expressed on the apical membranes of Caco-2 cells. PMID:24861932

  11. In vitro inhibition of salicylic acid derivatives on human cytosolic carbonic anhydrase isozymes I and II.

    PubMed

    Bayram, Esra; Senturk, Murat; Kufrevioglu, O Irfan; Supuran, Claudiu T

    2008-10-15

    The inhibition of two human cytosolic carbonic anhydrase (hCA, EC 4.2.1.1) isozymes, hCA I and II, with a series of salicylic acid derivatives was investigated by using the esterase method with 4-nitrophenyl acetate as substrate. IC(50) values for sulfasalazine, diflunisal, 5-chlorosalicylic acid, dinitrosalicylic acid, 4-aminosalicylic acid, 4-sulfosalicylic acid, 5-sulfosalicylic acid, salicylic acid, acetylsalicylic acid (aspirin) and 3-metylsalicylic acid were of 3.04 microM, 3.38 microM, 4.07 microM, 7.64 microM, 0.13 mM, 0.29 mM, 0.42 mM, 0.56 mM, 2.71 mM and 3.07 mM for hCA I and of 4.49 microM, 2.70 microM, 0.72 microM, 2.80 microM, 0.75 mM, 0.72 mM, 0.29 mM, 0.68 mM, 1.16 mM and 4.70 mM for hCA II, respectively. Lineweaver-Burk plots were also used for the determination of the inhibition mechanism of these substituted phenols, most of which were noncompetitive inhibitors with this substrate. Some salicylic acid derivatives investigated here showed effective hCA I and II inhibitory activity, and might be used as leads for generating enzyme inhibitors eventually targeting other isoforms which have not been assayed yet for their interactions with such agents.

  12. Free and bound cinnamic acid derivatives in corsica sweet blond oranges.

    PubMed

    Carrera, Eric; El Kebir, Mohamed Vall Ould; Jacquemond, Camille; Luro, François; Lozano, Yves; Gaydou, Emile M

    2010-03-01

    Total determination of cinnamic acids (CA), including hydroxycinnamic acid derivatives is generally not accurate since, during hydrolysis, a possible degradation of dihydroxy CA such as caffeic acid could occur. Evaluations of CA (ferulic, p-coumaric, sinapic, cinnamic and caffeic acids) before and after hydrolysis have been undertaken using standards and either with or without addition of ascorbic acid and EDTA. The method was then applied to the determination of free and bound CA in five blond cultivars (Navelina, Washington navel, Pera, Salustiana and Valencia late) of sweet oranges [Citrus sinensis (L.) Osb.]. Four parts of the fruits (peel juice, flavedo, albedo and juice) have been investigated. Results show that CA are mainly bound (86% up to 92%) in the four fruit parts. The mean of total CA contents was found to be higher in peel juice (1.5 g kg(-1)) in comparison with flavedo (0.7 g kg(-1)), albedo (0.1 g kg(-1)) and juice (0.6 g kg(-1)). Free and bound ferulic acid represented 55-70% of CA in juices, followed by p-coumaric acid (20%), sinapic acid (10%) and caffeic acid (9%). Total contents of each CA in the four fruit parts are discussed and show the potential interest in orange peel wastes. PMID:20420324

  13. Growth behavior of anodic oxide formed by aluminum anodizing in glutaric and its derivative acid electrolytes

    NASA Astrophysics Data System (ADS)

    Nakajima, Daiki; Kikuchi, Tatsuya; Natsui, Shungo; Suzuki, Ryosuke O.

    2014-12-01

    The growth behavior of anodic oxide films formed via anodizing in glutaric and its derivative acid solutions was investigated based on the acid dissociation constants of electrolytes. High-purity aluminum foils were anodized in glutaric, ketoglutaric, and acetonedicarboxylic acid solutions under various electrochemical conditions. A thin barrier anodic oxide film grew uniformly on the aluminum substrate by glutaric acid anodizing, and further anodizing caused the film to breakdown due to a high electric field. In contrast, an anodic porous alumina film with a submicrometer-scale cell diameter was successfully formed by ketoglutaric acid anodizing at 293 K. However, the increase and decrease in the temperature of the ketoglutaric acid resulted in non-uniform oxide growth and localized pitting corrosion of the aluminum substrate. An anodic porous alumina film could also be fabricated by acetonedicarboxylic acid anodizing due to the relatively low dissociation constants associated with the acid. Acid dissociation constants are an important factor for the fabrication of anodic porous alumina films.

  14. Simultaneous determination of 2-naphthoxyacetic acid and indole-3-acetic acid by first derivation synchronous fluorescence spectroscopy

    NASA Astrophysics Data System (ADS)

    Liu, Xiangxiang; Wan, Yiqun

    2013-07-01

    A simple, rapid, sensitive and selective method for simultaneously determining 2-naphthoxyacetic acid (BNOA) and Indole-3-Acetic Acid (IAA) in mixtures has been developed using derivation synchronous fluorescence spectroscopy based on their synchronous fluorescence. The synchronous fluorescence spectra were obtained with Δλ = 100 nm in a pH 8.5 NaH2PO4-NaOH buffer solution, and the detected wavelengths of quantitative analysis were set at 239 nm for BNOA and 293 nm for IAA respectively. The over lapped fluorescence spectra were well separated by the synchronous derivative method. Under optimized conditions, the limits of detection (LOD) were 0.003 μg/mL for BNOA and 0.012 μg/mL for IAA. This method is simple and expeditious, and it has been successfully applied to the determination of 2-naphthoxyacetic acid and indole-3-acetic acid in fruit juice samples with satisfactory results. The samples were only filtrated through a 0.45 μm membrane filter, which was free from the tedious separation procedures. The obtaining recoveries were in the range of 83.88-87.43% for BNOA and 80.76-86.68% for IAA, and the relative standard deviations were all less than 5.0%. Statistical comparison of the results with high performance liquid chromatography Mass Spectrometry (HPLC-MS) method revealed good agreement and proved that there were no significant difference in the accuracy and precision between these two methods.

  15. Monitoring of the fermentation media of citric acid by the trimethylsilyl derivatives of the organic acids formed.

    PubMed

    Ghassempour, Alireza; Nojavan, Saeed; Talebpour, Zahra; Amiri, Ali Asghar; Najafi, Nahid Mashkouri

    2004-10-20

    In this approach, a derivatization method is described for monitoring of organic acids in fermentation media without any separation step. The aqueous phase of fermentation media was evaporated and heated in a silylation reagent to form trimethylsilyl (TMS) derivatives. The silylated compounds are analyzed by 29Si nuclear magnetic resonance (29Si NMR) and gas chromatography-mass spectrometry (GC-MS). 29Si NMR can qualitatively monitor the components produced in the Krebs cycle. Quantification of these compounds is investigated by using selected ion monitoring mode of mass spectrometry. In this mode, mass to charge (m/z) values of their [M - 15]+ ions, which are 465, 275, 247, 221, 335, 251, and 313 of TMS derivatives of citric, alpha-ketoglutaric, succinic, fumaric, l-malic, oxaloacetic, and palmitic (as an internal standard), acids, respectively, are used. The limit of detection and the linear working range for derivatized citric acid were found to be 0.1 mg L(-1) and 10-3 x 10(4) mg L(-1). The relative standard deviation of the method for five replicates was 2.1%. The average recovery efficiency for citric acid added to culture media was approximately 97.2%. Quantitative results of GC-MS are compared with those obtained by an ultraviolet-visible method.

  16. Substrate-specific effects of pirinixic acid derivatives on ABCB1-mediated drug transport

    PubMed Central

    Michaelis, Martin; Rothweiler, Florian; Wurglics, Mario; Aniceto, Natália; Dittrich, Michaela; Zettl, Heiko; Wiese, Michael; Wass, Mark; Ghafourian, Taravat; Schubert-Zsilavecz, Manfred; Cinatl, Jindrich

    2016-01-01

    Pirinixic acid derivatives, a new class of drug candidates for a range of diseases, interfere with targets including PPARα, PPARγ, 5-lipoxygenase (5-LO), and microsomal prostaglandin and E2 synthase-1 (mPGES1). Since 5-LO, mPGES1, PPARα, and PPARγ represent potential anti-cancer drug targets, we here investigated the effects of 39 pirinixic acid derivatives on prostate cancer (PC-3) and neuroblastoma (UKF-NB-3) cell viability and, subsequently, the effects of selected compounds on drug-resistant neuroblastoma cells. Few compounds affected cancer cell viability in low micromolar concentrations but there was no correlation between the anti-cancer effects and the effects on 5-LO, mPGES1, PPARα, or PPARγ. Most strikingly, pirinixic acid derivatives interfered with drug transport by the ATP-binding cassette (ABC) transporter ABCB1 in a drug-specific fashion. LP117, the compound that exerted the strongest effect on ABCB1, interfered in the investigated concentrations of up to 2μM with the ABCB1-mediated transport of vincristine, vinorelbine, actinomycin D, paclitaxel, and calcein-AM but not of doxorubicin, rhodamine 123, or JC-1. In silico docking studies identified differences in the interaction profiles of the investigated ABCB1 substrates with the known ABCB1 binding sites that may explain the substrate-specific effects of LP117. Thus, pirinixic acid derivatives may offer potential as drug-specific modulators of ABCB1-mediated drug transport. PMID:26887049

  17. An Overview of Stereoselective Synthesis of α-Aminophosphonic Acids and Derivatives

    PubMed Central

    Ordóñez, Mario; Rojas-Cabrera, Haydée; Cativiela, Carlos

    2009-01-01

    An overview of all methodologies published during the last few years focused to the stereoselective (diastereoselective or enantioselective) synthesis of α-aminophosphonic acids and derivatives is reported. The procedures have been classified according a retrosynthetic strategy and taking into account the formation of each one of the bonds connected to the chiral centre. PMID:20871799

  18. Syntheses of fluorooxindole and 2-fluoro-2-arylacetic acid derivatives from diethyl 2-fluoromalonate ester

    PubMed Central

    Harsanyi, Antal; Yufit, Dmitri S; Howard, Judith AK

    2014-01-01

    Summary Diethyl 2-fluoromalonate ester is utilised as a building block for the synthesis of 2-fluoro-2-arylacetic acid and fluorooxindole derivatives by a strategy involving nucleophilic aromatic substitution reactions with ortho-fluoronitrobenzene substrates followed by decarboxylation, esterification and reductive cyclisation processes. PMID:24991270

  19. Nonmetal catalyzed insertion reactions of diazocarbonyls to acid derivatives in fluorinated alcohols.

    PubMed

    Dumitrescu, Lidia; Azzouzi-Zriba, Kaouther; Bonnet-Delpon, Danièle; Crousse, Benoit

    2011-02-18

    The insertion reaction of diazocarbonyls to acids could be performed smoothly in fluorinated alcohols in the absence of metal catalyst. This new procedure allowed the chemoselective preparation of various functionalized compounds such as acyloxyesters, depsipeptides, and sulfonate, phosphonate, or boronate derivatives.

  20. Diet derived phenolic acids regulate osteoblast and adipocyte lineage commitment and differentiation in young mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A blueberry (BB) supplemented diet previously has been shown to significantly stimulate bone formation in rapidly growing male and female rodents. Phenolic acids (PAs) are metabolites derived from polyphenols found in fruits and vegetables as a result of the actions of gut bacteria, and they were fo...

  1. Heterogeneous catalysts for the transformation of fatty acid triglycerides and their derivatives to fuel hydrocarbons

    NASA Astrophysics Data System (ADS)

    Yakovlev, Vadim A.; Khromova, Sofia A.; Bukhtiyarov, Valerii I.

    2011-10-01

    The results of studies devoted to the catalysts for transformation of fatty acid triglycerides and their derivatives to fuel hydrocarbons are presented and described systematically. Various approaches to the use of heterogeneous catalysts for the production of biofuel from these raw materials are considered. The bibliography includes 134 references.

  2. Correlation between chemical structure and rodent repellency of benzoic acid derivatives

    USGS Publications Warehouse

    Fearn, J.E.; DeWitt, J.B.

    1965-01-01

    Sixty-five benzoic acid derivatives were either prepared or obtained from commercial concerns, tested for rat repellency, and their indices of repellency computed. The data from these tests were considered analytically for any correlation between chemical structure and rat repellency. The results suggest a qualitative relationship which is useful in deciding probability of repellency in other compounds.

  3. Antioxidant glucosylated caffeoylquinic acid derivatives in the invasive tropical soda apple, Solanum viarum

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The eggplant (Solanum melongena) and other species within the “spiny solanums” (Solanum subgenus Leptostemonum) contain diverse and abundant antioxidant caffeoylquinic acid (CQA) derivatives. The fruit of an aggressive invasive species in the spiny solanums, Solanum viarum, contain numerous CQA deri...

  4. Tracking of Drug Release and Material Fate for Naturally Derived Omega-3 Fatty Acid Biomaterials.

    PubMed

    Faucher, Keith M; Artzi, Natalie; Beck, Moshe; Beckerman, Rita; Moodie, Geoff; Albergo, Theresa; Conroy, Suzanne; Dale, Alicia; Corbeil, Scott; Martakos, Paul; Edelman, Elazer R

    2016-03-01

    In vitro and in vivo studies were conducted on omega-3 fatty acid-derived biomaterials to determine their utility as an implantable material for adhesion prevention following soft tissue hernia repair and as a means to allow for the local delivery of antimicrobial or antibiofilm agents. Naturally derived biomaterials offer several advantages over synthetic materials in the field of medical device development. These advantages include enhanced biocompatibility, elimination of risks posed by the presence of toxic catalysts and chemical crosslinking agents, and derivation from renewable resources. Omega-3 fatty acids are readily available from fish and plant sources and can be used to create implantable biomaterials either as a stand-alone device or as a device coating that can be utilized in local drug delivery applications. In-depth characterization of material erosion degradation over time using non-destructive imaging and chemical characterization techniques provided mechanistic insight into material structure: function relationship. This in turn guided rational tailoring of the material based on varying fatty acid composition to control material residence time and hence drug release. These studies demonstrate the utility of omega-3 fatty acid derived biomaterials as an absorbable material for soft tissue hernia repair and drug delivery applications.

  5. Nickel(II) and copper(II) complexes with humic acid anions and their derivatives

    SciTech Connect

    Ryabova, I.N.

    2008-01-15

    Complexation of Ni(II) and Cu(II) in aqueous solutions with anions of humic acids, extracted from naturally oxidized coal, and with their hydroxymethyl derivatives is studied spectrophotometrically and potentiometrically. The complexation stoichiometry and the stability constants of the complexes are determined.

  6. Production of Fatty Acid-derived valuable chemicals in synthetic microbes.

    PubMed

    Yu, Ai-Qun; Pratomo Juwono, Nina Kurniasih; Leong, Susanna Su Jan; Chang, Matthew Wook

    2014-01-01

    Fatty acid derivatives, such as hydroxy fatty acids, fatty alcohols, fatty acid methyl/ethyl esters, and fatty alka(e)nes, have a wide range of industrial applications including plastics, lubricants, and fuels. Currently, these chemicals are obtained mainly through chemical synthesis, which is complex and costly, and their availability from natural biological sources is extremely limited. Metabolic engineering of microorganisms has provided a platform for effective production of these valuable biochemicals. Notably, synthetic biology-based metabolic engineering strategies have been extensively applied to refactor microorganisms for improved biochemical production. Here, we reviewed: (i) the current status of metabolic engineering of microbes that produce fatty acid-derived valuable chemicals, and (ii) the recent progress of synthetic biology approaches that assist metabolic engineering, such as mRNA secondary structure engineering, sensor-regulator system, regulatable expression system, ultrasensitive input/output control system, and computer science-based design of complex gene circuits. Furthermore, key challenges and strategies were discussed. Finally, we concluded that synthetic biology provides useful metabolic engineering strategies for economically viable production of fatty acid-derived valuable chemicals in engineered microbes.

  7. Production of Fatty Acid-Derived Valuable Chemicals in Synthetic Microbes

    PubMed Central

    Yu, Ai-Qun; Pratomo Juwono, Nina Kurniasih; Leong, Susanna Su Jan; Chang, Matthew Wook

    2014-01-01

    Fatty acid derivatives, such as hydroxy fatty acids, fatty alcohols, fatty acid methyl/ethyl esters, and fatty alka(e)nes, have a wide range of industrial applications including plastics, lubricants, and fuels. Currently, these chemicals are obtained mainly through chemical synthesis, which is complex and costly, and their availability from natural biological sources is extremely limited. Metabolic engineering of microorganisms has provided a platform for effective production of these valuable biochemicals. Notably, synthetic biology-based metabolic engineering strategies have been extensively applied to refactor microorganisms for improved biochemical production. Here, we reviewed: (i) the current status of metabolic engineering of microbes that produce fatty acid-derived valuable chemicals, and (ii) the recent progress of synthetic biology approaches that assist metabolic engineering, such as mRNA secondary structure engineering, sensor-regulator system, regulatable expression system, ultrasensitive input/output control system, and computer science-based design of complex gene circuits. Furthermore, key challenges and strategies were discussed. Finally, we concluded that synthetic biology provides useful metabolic engineering strategies for economically viable production of fatty acid-derived valuable chemicals in engineered microbes. PMID:25566540

  8. Studies on chemical modification and biology of a natural product, gambogic acid (II): Synthesis and bioevaluation of gambogellic acid and its derivatives from gambogic acid as antitumor agents.

    PubMed

    Wang, Jinxin; Ma, Junhai; You, Qidong; Zhao, Li; Wang, Fan; Li, Chong; Guo, Qinglong

    2010-09-01

    Gambogic acid (GA) has been reported to be a potent apoptosis inducer. The fact that it is amenable to chemical modification makes GA an attractive molecule for the development of anticancer agents. We firstly reported the synthesis of gambogellic acid, which was generated under acid catalysis from readily available GA by a base-catalyzed diene intramolecular annelation. Sequentially, thirteen new compounds were synthesized and their inhibitory activity on HT-29, Bel-7402, BGC-823, and A549 cell lines were evaluated in vitro by MTT assay, and (38, 40)-epoxy-33-chlorogambogellic acid (4) was identified as a BGC-823 cell apoptosis inducer through MTT cell assay, observations of morphological changes, and Annexin-V/PI double-staining assay. Compound 4 showed significant effects in inducing apoptosis and might serve as a potential lead compound for discovery of new anticancer drugs. Further structure-activity relationships (SARs) of gambogic acid derivatives were discussed.

  9. Medicinal importance of gallic acid and its ester derivatives: a patent review.

    PubMed

    Choubey, Sneha; Varughese, Lesley Rachel; Kumar, Vinod; Beniwal, Vikas

    2015-01-01

    Gallic acid and its derivatives have a large number of applications in various fields of science. In nature, these compounds are widely distributed in plants and fruits, and thus they are being used as food stuffs, preservatives, etc. directly or indirectly by human community. They have also been implicated as anticarcinogenic, antimicrobial, antimutagenic, antiangiogenic and anti-inflammatory agents besides their use in treating critical diseases like depression, cancer, microbial infections, lipid-related diseases, etc. Herein, an attempt has been made to summarize the important uses of gallic acid derivatives which have extensively been disclosed particularly in various patents. This review would certainly create a great interest of the scientific community toward the developments and uses of gallic acid based compounds in the future.

  10. Spectroscopic studies on gallic acid and its azo derivatives and their iron(III) complexes.

    PubMed

    Masoud, Mamdouh S; Ali, Alaa E; Haggag, Sawsan S; Nasr, Nessma M

    2014-01-01

    Azo gallic derivatives and their iron(III) complexes were synthesized and characterized. The stereochemistry and the mode of bonding of the complexes were achieved based on elemental analysis, UV-Vis and IR. The thermal behaviors of the complexes were studied. The effect of pH on the electronic absorption spectra of gallic acid and its azo derivatives are discussed. Different spectroscopic methods (molar ratio, straight line method, continuous variation, slope ratio and successive method) are applied for determination of stoichiometry and pK values for the complex formation of gallic acid with iron(III) in aqueous media. Iron(III) complexes of gallic acid is formed with different ratio: 1:1, 1:2, 1:3 and 1:4 (M:L).

  11. Search for novel histone deacetylase inhibitors. Part II: design and synthesis of novel isoferulic acid derivatives.

    PubMed

    Lu, Wen; Wang, Fang; Zhang, Tao; Dong, Jinyun; Gao, Hongping; Su, Ping; Shi, Yaling; Zhang, Jie

    2014-05-01

    Previously, we described the discovery of potent ferulic acid-based histone deacetylase inhibitors (HDACIs) with halogeno-acetanilide as novel surface recognition moiety (SRM). In order to improve the affinity and activity of these HDACIs, twenty seven isoferulic acid derivatives were described herein. The majority of title compounds displayed potent HDAC inhibitory activity. In particular, IF5 and IF6 exhibited significant enzymatic inhibitory activities, with IC50 values of 0.73 ± 0.08 and 0.57 ± 0.16 μM, respectively. Furthermore, these compounds showed moderate antiproliferative activity against human cancer cells. Especially, IF6 displayed promising profile as an antitumor candidate with IC50 value of 3.91 ± 0.97 μM against HeLa cells. The results indicated that these isoferulic acid derivatives could serve as promising lead compounds for further optimization. PMID:24702857

  12. Medicinal importance of gallic acid and its ester derivatives: a patent review.

    PubMed

    Choubey, Sneha; Varughese, Lesley Rachel; Kumar, Vinod; Beniwal, Vikas

    2015-01-01

    Gallic acid and its derivatives have a large number of applications in various fields of science. In nature, these compounds are widely distributed in plants and fruits, and thus they are being used as food stuffs, preservatives, etc. directly or indirectly by human community. They have also been implicated as anticarcinogenic, antimicrobial, antimutagenic, antiangiogenic and anti-inflammatory agents besides their use in treating critical diseases like depression, cancer, microbial infections, lipid-related diseases, etc. Herein, an attempt has been made to summarize the important uses of gallic acid derivatives which have extensively been disclosed particularly in various patents. This review would certainly create a great interest of the scientific community toward the developments and uses of gallic acid based compounds in the future. PMID:26174568

  13. Synthesis and comparison of antioxidant properties of indole-based melatonin analogue indole amino Acid derivatives.

    PubMed

    Suzen, Sibel; Cihaner, Seyhan Sezen; Coban, Tulay

    2012-01-01

    Increased levels of reactive oxygen species attributed to oxidative stress have been found to be responsible for the development of some vital diseases such as cardiovascular, neurodegenerative and autoimmune diseases. Recently, it was observed that melatonin is a highly important antioxidant, and melatonin analogues are under investigation to find out improved antioxidant activity. In this study, 14 melatonin -based analogue indole amino acid and N-protected amino acid derivatives were synthesized and elucidated spectrometrically. To investigate the antioxidant activity of the synthesized compounds and to compare with melatonin, butylhydroxytoluene and vitamin E, lipid peroxidation inhibition and 2,2-diphenyl-1-picrylhydrazyl radical-scavenging activities were tested. The results indicated that the synthesized new indole amino acid derivatives have similar activities to melatonin in 2,2-diphenyl-1-picrylhydrazyl radical-scavenging activity assay but more potent activities in lipid peroxidation inhibition assay.

  14. Synthesis, structure and cytotoxic activity of acetylenic derivatives of betulonic and betulinic acids

    NASA Astrophysics Data System (ADS)

    Bębenek, Ewa; Chrobak, Elwira; Wietrzyk, Joanna; Kadela, Monika; Chrobak, Artur; Kusz, Joachim; Książek, Maria; Jastrzębska, Maria; Boryczka, Stanisław

    2016-02-01

    A series of acetylenic derivatives of betulonic and betulinic acids has been synthesized and characterized by 1H and 13C NMR, IR and MS spectroscopy. The structure of propargyl betulonate 4 and propargyl betulinate-DMF solvate 8A was solved by X-ray diffraction. Thermal properties were examined using a DSC technique. The resulting alkynyl derivatives, as well as betulin 1 and betulinic acid 3, were evaluated in vitro for their cytotoxic activity against human T47D breast cancer, CCRF/CEM leukemia, SW707 colorectal, murine P388 leukemia and BALB3T3 normal fibroblasts cell lines. Several of the obtained compounds have a favorable cytotoxic profile than betulin 1. Propargyl betulinate 8 was the most active derivative, being up to 3-fold more potent than betulin 1 against the human leukemia (CCRF/CEM) cell line, with an IC50 value of 3.9 μg/mL.

  15. In situ forming hydrogels of hyaluronic acid and inulin derivatives for cartilage regeneration.

    PubMed

    Palumbo, Fabio S; Fiorica, Calogero; Di Stefano, Mauro; Pitarresi, Giovanna; Gulino, Alessandro; Agnello, Stefano; Giammona, Gaetano

    2015-05-20

    An in situ forming hydrogel obtained by crosslinking of amino functionalized hyaluronic acid derivatives with divinylsulfone functionalized inulin (INU-DV) has been here designed and characterized. In particular two hyaluronic acid derivatives bearing respectively a pendant ethylenediamino (EDA) portion (HA-EDA) and both EDA and octadecyl pendant groups (HA-EDA-C18) were crosslinked through an azo-Michael reaction with INU-DV. Gelation time and consumption of DV portions have been evaluated on hydrogel obtained using HA-EDA and HA-EDA-C18 derivatives with a concentration of 3% w/v and a ratio 80/20 w/w respect to the crosslinker INU-DV. The presence of pendant C18 chains improves mechanical performances of hydrogels and decreases the susceptibility to hyaluronidase hydrolysis. Bovine chondrocytes, encapsulated during crosslinking, sufficiently survive and efficiently proliferate until 28 days of analysis.

  16. Synthesis, structure and cytotoxic activity of acetylenic derivatives of betulonic and betulinic acids

    NASA Astrophysics Data System (ADS)

    Bębenek, Ewa; Chrobak, Elwira; Wietrzyk, Joanna; Kadela, Monika; Chrobak, Artur; Kusz, Joachim; Książek, Maria; Jastrzębska, Maria; Boryczka, Stanisław

    2016-02-01

    A series of acetylenic derivatives of betulonic and betulinic acids has been synthesized and characterized by 1H and 13C NMR, IR and MS spectroscopy. The structure of propargyl betulonate 4 and propargyl betulinate-DMF solvate 8A was solved by X-ray diffraction. Thermal properties were examined using a DSC technique. The resulting alkynyl derivatives, as well as betulin 1 and betulinic acid 3, were evaluated in vitro for their cytotoxic activity against human T47D breast cancer, CCRF/CEM leukemia, SW707 colorectal, murine P388 leukemia and BALB3T3 normal fibroblasts cell lines. Several of the obtained compounds have a favorable cytotoxic profile than betulin 1. Propargyl betulinate 8 was the most active derivative, being up to 3-fold more potent than betulin 1 against the human leukemia (CCRF/CEM) cell line, with an IC50 value of 3.9 μg/mL.

  17. Angiotensin II modification by decomposition products of linoleic acid-derived lipid hydroperoxide.

    PubMed

    Takahashi, Ryo; Goto, Takaaki; Oe, Tomoyuki; Lee, Seon Hwa

    2015-09-01

    Polyunsaturated fatty acids are highly susceptible to oxidation induced by reactive oxygen species and enzymes, leading to the formation of lipid hydroperoxides. The linoleic acid (LA)-derived hydroperoxide, 13-hydroperoxyoctadecadienoic acid (HPODE) undergoes homolytic decomposition to reactive aldehydes, 4-oxo-2(E)-nonenal (ONE), 4-hydroxy-2(E)-nonenal, trans-4,5-epoxy-2(E)-decenal (EDE), and 4-hydroperoxy-2(E)-nonenal (HPNE), which can covalently modify peptides and proteins. ONE and HNE have been shown to react with angiotensin (Ang) II (DRVYIHPF) and modify the N-terminus, Arg(2), and His(6). ONE-derived pyruvamide-Ang II (Ang P) alters the biological activities of Ang II considerably. The present study revealed that EDE and HPNE preferentially modified the N-terminus and His(6) of Ang II. In addition to the N-substituted pyrrole of [N-C4H2]-Ang II and Michael addition products of [His(6)(EDE)]-Ang II, hydrated forms were detected as major products, suggesting considerable involvement of the vicinal dihydrodiol (formed by epoxide hydration) in EDE-derived protein modification in vivo. Substantial amounts of [N-(EDE-H2O)]-Ang II isomers were also formed and their synthetic pathway might involve the tautomerization of a carbinolamine intermediate, followed by intramolecular cyclization and dehydration. The main HPNE-derived products were [His(6)(HPNE)]-Ang II and [N-(HPNE-H2O)]-Ang II. However, ONE, HNE, and malondialdehyde-derived modifications were dominant, because HPNE is a precursor of these aldehydes. A mixture of 13-HPODE and [(13)C18]-13-HPODE (1:1) was then used to determine the major modifications derived from LA peroxidation. The characteristic doublet (1:1) observed in the mass spectrum and the mass difference of the [M+H](+) doublet aided the identification of Ang P (N-terminal α-ketoamide), [N-ONE]-Ang II (4-ketoamide), [Arg(2)(ONE-H2O)]-Ang II, [His(6)(HNE)]-Ang II (Michael addition product), [N-C4H2]-Ang II (EDE-derived N-substituted pyrrole

  18. Angiotensin II modification by decomposition products of linoleic acid-derived lipid hydroperoxide.

    PubMed

    Takahashi, Ryo; Goto, Takaaki; Oe, Tomoyuki; Lee, Seon Hwa

    2015-09-01

    Polyunsaturated fatty acids are highly susceptible to oxidation induced by reactive oxygen species and enzymes, leading to the formation of lipid hydroperoxides. The linoleic acid (LA)-derived hydroperoxide, 13-hydroperoxyoctadecadienoic acid (HPODE) undergoes homolytic decomposition to reactive aldehydes, 4-oxo-2(E)-nonenal (ONE), 4-hydroxy-2(E)-nonenal, trans-4,5-epoxy-2(E)-decenal (EDE), and 4-hydroperoxy-2(E)-nonenal (HPNE), which can covalently modify peptides and proteins. ONE and HNE have been shown to react with angiotensin (Ang) II (DRVYIHPF) and modify the N-terminus, Arg(2), and His(6). ONE-derived pyruvamide-Ang II (Ang P) alters the biological activities of Ang II considerably. The present study revealed that EDE and HPNE preferentially modified the N-terminus and His(6) of Ang II. In addition to the N-substituted pyrrole of [N-C4H2]-Ang II and Michael addition products of [His(6)(EDE)]-Ang II, hydrated forms were detected as major products, suggesting considerable involvement of the vicinal dihydrodiol (formed by epoxide hydration) in EDE-derived protein modification in vivo. Substantial amounts of [N-(EDE-H2O)]-Ang II isomers were also formed and their synthetic pathway might involve the tautomerization of a carbinolamine intermediate, followed by intramolecular cyclization and dehydration. The main HPNE-derived products were [His(6)(HPNE)]-Ang II and [N-(HPNE-H2O)]-Ang II. However, ONE, HNE, and malondialdehyde-derived modifications were dominant, because HPNE is a precursor of these aldehydes. A mixture of 13-HPODE and [(13)C18]-13-HPODE (1:1) was then used to determine the major modifications derived from LA peroxidation. The characteristic doublet (1:1) observed in the mass spectrum and the mass difference of the [M+H](+) doublet aided the identification of Ang P (N-terminal α-ketoamide), [N-ONE]-Ang II (4-ketoamide), [Arg(2)(ONE-H2O)]-Ang II, [His(6)(HNE)]-Ang II (Michael addition product), [N-C4H2]-Ang II (EDE-derived N-substituted pyrrole

  19. Enhanced lignin monomer production caused by cinnamic Acid and its hydroxylated derivatives inhibits soybean root growth.

    PubMed

    Lima, Rogério Barbosa; Salvador, Victor Hugo; dos Santos, Wanderley Dantas; Bubna, Gisele Adriana; Finger-Teixeira, Aline; Soares, Anderson Ricardo; Marchiosi, Rogério; Ferrarese, Maria de Lourdes Lucio; Ferrarese-Filho, Osvaldo

    2013-01-01

    Cinnamic acid and its hydroxylated derivatives (p-coumaric, caffeic, ferulic and sinapic acids) are known allelochemicals that affect the seed germination and root growth of many plant species. Recent studies have indicated that the reduction of root growth by these allelochemicals is associated with premature cell wall lignification. We hypothesized that an influx of these compounds into the phenylpropanoid pathway increases the lignin monomer content and reduces the root growth. To confirm this hypothesis, we evaluated the effects of cinnamic, p-coumaric, caffeic, ferulic and sinapic acids on soybean root growth, lignin and the composition of p-hydroxyphenyl (H), guaiacyl (G) and syringyl (S) monomers. To this end, three-day-old seedlings were cultivated in nutrient solution with or without allelochemical (or selective enzymatic inhibitors of the phenylpropanoid pathway) in a growth chamber for 24 h. In general, the results showed that 1) cinnamic, p-coumaric, caffeic and ferulic acids reduced root growth and increased lignin content; 2) cinnamic and p-coumaric acids increased p-hydroxyphenyl (H) monomer content, whereas p-coumaric, caffeic and ferulic acids increased guaiacyl (G) content, and sinapic acid increased sinapyl (S) content; 3) when applied in conjunction with piperonylic acid (PIP, an inhibitor of the cinnamate 4-hydroxylase, C4H), cinnamic acid reduced H, G and S contents; and 4) when applied in conjunction with 3,4-(methylenedioxy)cinnamic acid (MDCA, an inhibitor of the 4-coumarate:CoA ligase, 4CL), p-coumaric acid reduced H, G and S contents, whereas caffeic, ferulic and sinapic acids reduced G and S contents. These results confirm our hypothesis that exogenously applied allelochemicals are channeled into the phenylpropanoid pathway causing excessive production of lignin and its main monomers. By consequence, an enhanced stiffening of the cell wall restricts soybean root growth.

  20. RNA:DNA Ratio and Other Nucleic Acid Derived Indices in Marine Ecology

    PubMed Central

    Chícharo, Maria Alexandra; Chícharo, Luis

    2008-01-01

    Some of most used indicators in marine ecology are nucleic acid-derived indices. They can be divided by target levels in three groups: 1) at the organism level as ecophysiologic indicators, indicators such as RNA:DNA ratios, DNA:dry weight and RNA:protein, 2) at the population level, indicators such as growth rate, starvation incidence or fisheries impact indicators, and 3) at the community level, indicators such as trophic interactions, exergy indices and prey identification. The nucleic acids derived indices, especially RNA:DNA ratio, have been applied with success as indicators of nutritional condition, well been and growth in marine organisms. They are also useful as indicators of natural or anthropogenic impacts in marine population and communities, such as upwelling or dredge fisheries, respectively. They can help in understanding important issues of marine ecology such as trophic interactions in marine environment, fish and invertebrate recruitment failure and biodiversity changes, without laborious work of counting, measuring and identification of small marine organisms. Besides the objective of integrate nucleic acid derived indices across levels of organization, the paper will also include a general characterization of most used nucleic acid derived indices in marine ecology and also advantages and limitations of them. We can conclude that using indicators, such RNA:DNA ratios and other nucleic acids derived indices concomitantly with organism and ecosystems measures of responses to climate change (distribution, abundance, activity, metabolic rate, survival) will allow for the development of more rigorous and realistic predictions of the effects of anthropogenic climate change on marine systems. PMID:19325815

  1. Photophysical, photochemical, and thermodynamic properties of shikimic acid derivatives: calycin and rhizocarpic acid (lichens).

    PubMed

    Hidalgo, M E; Fernández, E; Ponce, M; Rubio, C; Quilhot, W

    2002-04-01

    Photophysical and photochemical parameters of the lichen metabolites calycin and rhizocarpic acid were determined. Experiments were carried out in micellar solutions of 3% Brij 35, at pH 2 and 12, and in acetonitrile. Both metabolites absorb in the UV-A and UV-B regions, and emit fluorescence in the visible region of the solar spectrum. Shifts were not observed in the absorption spectra, at pH 2 and 12. The low phi(c), between 10(-5) and 10(-2), shows that both compounds are photostable in the experimental conditions. For rhizocarpic acid, two values of pK(a) were obtained: 5.1 corresponding to the hydroxyl group, and 9.0 corresponding to the protonated nitrogen. Calycin presents only one value of pK(a): 4.9, that is attributed to the hydroxyl group. L-(+)-Gluconic-gamma-lactonic acid was used as a reference model; the compound showed greater photoinstability, demonstrating that the photodegradation observed occurs mainly in the oxolane carbonylic ring.

  2. Potential biological applications of bio-based anacardic acids and their derivatives.

    PubMed

    Hamad, Fatma B; Mubofu, Egid B

    2015-01-01

    Cashew nut shells (CNS), which are agro wastes from cashew nut processing factories, have proven to be among the most versatile bio-based renewable materials in the search for functional materials and chemicals from renewable resources. CNS are produced in the cashew nut processing process as waste, but they contain cashew nut shell liquid (CNSL) up to about 30-35 wt. % of the nut shell weight depending on the method of extraction. CNSL is a mixture of anacardic acid, cardanol, cardol, and methyl cardol, and the structures of these phenols offer opportunities for the development of diverse products. For anacardic acid, the combination of phenolic, carboxylic, and a 15-carbon alkyl side chain functional group makes it attractive in biological applications or as a synthon for the synthesis of a multitude of bioactive compounds. Anacardic acid, which is about 65% of a CNSL mixture, can be extracted from the agro waste. This shows that CNS waste can be used to extract useful chemicals and thus provide alternative green sources of chemicals, apart from relying only on the otherwise declining petroleum based sources. This paper reviews the potential of anacardic acids and their semi-synthetic derivatives for antibacterial, antitumor, and antioxidant activities. The review focuses on natural anacardic acids from CNS and other plants and their semi-synthetic derivatives as possible lead compounds in medicine. In addition, the use of anacardic acid as a starting material for the synthesis of various biologically active compounds and complexes is reported. PMID:25894225

  3. Potential biological applications of bio-based anacardic acids and their derivatives.

    PubMed

    Hamad, Fatma B; Mubofu, Egid B

    2015-01-01

    Cashew nut shells (CNS), which are agro wastes from cashew nut processing factories, have proven to be among the most versatile bio-based renewable materials in the search for functional materials and chemicals from renewable resources. CNS are produced in the cashew nut processing process as waste, but they contain cashew nut shell liquid (CNSL) up to about 30-35 wt. % of the nut shell weight depending on the method of extraction. CNSL is a mixture of anacardic acid, cardanol, cardol, and methyl cardol, and the structures of these phenols offer opportunities for the development of diverse products. For anacardic acid, the combination of phenolic, carboxylic, and a 15-carbon alkyl side chain functional group makes it attractive in biological applications or as a synthon for the synthesis of a multitude of bioactive compounds. Anacardic acid, which is about 65% of a CNSL mixture, can be extracted from the agro waste. This shows that CNS waste can be used to extract useful chemicals and thus provide alternative green sources of chemicals, apart from relying only on the otherwise declining petroleum based sources. This paper reviews the potential of anacardic acids and their semi-synthetic derivatives for antibacterial, antitumor, and antioxidant activities. The review focuses on natural anacardic acids from CNS and other plants and their semi-synthetic derivatives as possible lead compounds in medicine. In addition, the use of anacardic acid as a starting material for the synthesis of various biologically active compounds and complexes is reported.

  4. Fermentation of biomass-derived glucuronic acid by pet expressing recombinants of E. coli B

    SciTech Connect

    Lawford, H.G.; Rousseau, J.D.

    1997-12-31

    The economics of large-scale production of fuel ethanol from biomass and wastes requires the efficient utilization of all the sugars derived from the hydrolysis of the heteropolymeric hemicellulose component of lignocellulosic feedstocks. Glucuronic and 4-0-methyl-glucuronic acids are major side chains in xylans of the grasses and hardwoods that have been targeted as potential feedstocks for the production of cellulosic ethanol. The amount of these acids is similar to that of arabinose, which is now being viewed as another potential substrate in the production of biomass-derived ethanol. This study compared the end-product distribution associated with the fermentation of D-glucose (Glc) and D-glucuronic acid (GlcUA) (as sole carbon and energy sources) by Escherichia coli B (ATCC 11303) and two different ethanologenic recombinants--a strain in which pet expression was via a multicopy plasmid (pLOI297) and a chromosomally integrated construct, strain KO11. pH-stat batch fermentations were conducted using a modified LB medium with 2% (w/v) Glc or GlcUA with the set-point for pH control at either 6.3 or 7.0. The nontransformed host culture produced only lactic acid from glucose, but fermentation of GlcUA yielded a mixture of ethanol, acetic, and lactic acids, with acetic acid being the predominant end-product. 73 refs., 6 figs., 2 tabs.

  5. Potential Biological Applications of Bio-Based Anacardic Acids and Their Derivatives

    PubMed Central

    Hamad, Fatma B.; Mubofu, Egid B.

    2015-01-01

    Cashew nut shells (CNS), which are agro wastes from cashew nut processing factories, have proven to be among the most versatile bio-based renewable materials in the search for functional materials and chemicals from renewable resources. CNS are produced in the cashew nut processing process as waste, but they contain cashew nut shell liquid (CNSL) up to about 30–35 wt. % of the nut shell weight depending on the method of extraction. CNSL is a mixture of anacardic acid, cardanol, cardol, and methyl cardol, and the structures of these phenols offer opportunities for the development of diverse products. For anacardic acid, the combination of phenolic, carboxylic, and a 15-carbon alkyl side chain functional group makes it attractive in biological applications or as a synthon for the synthesis of a multitude of bioactive compounds. Anacardic acid, which is about 65% of a CNSL mixture, can be extracted from the agro waste. This shows that CNS waste can be used to extract useful chemicals and thus provide alternative green sources of chemicals, apart from relying only on the otherwise declining petroleum based sources. This paper reviews the potential of anacardic acids and their semi-synthetic derivatives for antibacterial, antitumor, and antioxidant activities. The review focuses on natural anacardic acids from CNS and other plants and their semi-synthetic derivatives as possible lead compounds in medicine. In addition, the use of anacardic acid as a starting material for the synthesis of various biologically active compounds and complexes is reported. PMID:25894225

  6. Gastroprotective mechanisms of action of semisynthetic carnosic acid derivatives in human cells.

    PubMed

    Theoduloz, Cristina; Pertino, Mariano Walter; Schmeda-Hirschmann, Guillermo

    2014-01-06

    Carnosic acid (CA) and its semisynthetic derivatives display relevant gastroprotective effects on HCl/ethanol induced gastric lesions in mice. However, little is known on the mechanisms of action of the new compounds. The aim of the present work was to assess the gastroprotective action mechanisms of CA and its derivatives using human cell culture models. A human gastric adenocarcinoma cell line (AGS) and lung fibroblasts (MRC-5) were used to reveal the possible mechanisms involved. The ability of the compounds to protect cells against sodium taurocholate (NaT)-induced damage, and to increase the cellular reduced glutathione (GSH) and prostaglandin E2 (PGE2) content was determined using AGS cells. Stimulation of cell proliferation was studied employing MRC-5 fibroblasts. Carnosic acid and its derivatives 10-18 raised GSH levels in AGS cells. While CA did not increase the PGE2 content in AGS cells, all derivatives significantly stimulated PGE2 synthesis, the best effect being found for the 12-O-indolebutyrylmethylcarnosate 13. A significant increase in MRC-5 fibroblast proliferation was observed for the derivatives 7 and 16-18. The antioxidant effect of the compounds was assessed by the inhibition of lipid peroxidation in human erythrocyte membranes, scavenging of superoxide anion and DPPH discoloration assay. The new CA derivatives showed gastroprotective effects by different mechanisms, including protection against cell damage induced by NaT, increase in GSH content, stimulation of PGE2 synthesis and cell proliferation.

  7. Gastroprotective mechanisms of action of semisynthetic carnosic acid derivatives in human cells.

    PubMed

    Theoduloz, Cristina; Pertino, Mariano Walter; Schmeda-Hirschmann, Guillermo

    2013-01-01

    Carnosic acid (CA) and its semisynthetic derivatives display relevant gastroprotective effects on HCl/ethanol induced gastric lesions in mice. However, little is known on the mechanisms of action of the new compounds. The aim of the present work was to assess the gastroprotective action mechanisms of CA and its derivatives using human cell culture models. A human gastric adenocarcinoma cell line (AGS) and lung fibroblasts (MRC-5) were used to reveal the possible mechanisms involved. The ability of the compounds to protect cells against sodium taurocholate (NaT)-induced damage, and to increase the cellular reduced glutathione (GSH) and prostaglandin E2 (PGE2) content was determined using AGS cells. Stimulation of cell proliferation was studied employing MRC-5 fibroblasts. Carnosic acid and its derivatives 10-18 raised GSH levels in AGS cells. While CA did not increase the PGE2 content in AGS cells, all derivatives significantly stimulated PGE2 synthesis, the best effect being found for the 12-O-indolebutyrylmethylcarnosate 13. A significant increase in MRC-5 fibroblast proliferation was observed for the derivatives 7 and 16-18. The antioxidant effect of the compounds was assessed by the inhibition of lipid peroxidation in human erythrocyte membranes, scavenging of superoxide anion and DPPH discoloration assay. The new CA derivatives showed gastroprotective effects by different mechanisms, including protection against cell damage induced by NaT, increase in GSH content, stimulation of PGE2 synthesis and cell proliferation. PMID:24399049

  8. Aromatic and volatile acid intermediates observed during anaerobic metabolism of lignin-derived oligomers

    SciTech Connect

    Colberg, P.J.; Young, L.Y.

    1985-02-01

    Anaerobic enrichment cultures acclimated for 2 years to use a /sup 14/C-labeled, lignin-derived substrate with a molecular weight of 600 as a sole source of carbon were characterized by capillary and packed column gas chromatography. After acclimation, several of the active methanogenic organisms were inhibited with 2-bromoethanesulfonic acid, which suppressed methane formation and enhanced accumulation of a series of metabolic intermediates. Volatile fatty acids levels in 2-bromoethansulfonic acid-amended cultures were 10 times greater than those in the uninhibited, methane-forming organisms with acetate as the predominant component. Furthermore, in the 2-bromoethanesulfonic acid-amended organisms, almost half of the original substrate carbon was metabolized to 10 monaromatic compounds, with the most appreciable quantities accumulated as cinnamic, benzoic, caffeic, vanillic, and ferulic acids. 2-Bromoethanesulfonic acid seemed to effectively block CH/sub 4/ formation in the anaerobic food chain, resulting in the observed buildup of volatile fatty acids and monoaromatic intermediates. Neither fatty acids nor aromatic compounds were detected in the oligolignol substrate before its metabolism, suggesting that these anaerobic organisms have the ability to mediate the cleavage of the ..beta..-aryl-ether bond, the most common intermonomeric linkage in lignin, with the subsequent release of the observed constituent aromatic monomers.

  9. Aromatic and Volatile Acid Intermediates Observed during Anaerobic Metabolism of Lignin-Derived Oligomers

    PubMed Central

    Colberg, P. J.; Young, L. Y.

    1985-01-01

    Anaerobic enrichment cultures acclimated for 2 years to use a 14C-labeled, lignin-derived substrate with a molecular weight of 600 as a sole source of carbon were characterized by capillary and packed column gas chromatography. After acclimation, several of the active methanogenic consortia were inhibited with 2-bromoethanesulfonic acid, which suppressed methane formation and enhanced accumulation of a series of metabolic intermediates. Volatile fatty acids levels in 2-bromoethanesulfonic acid-amended cultures were 10 times greater than those in the uninhibited, methane-forming consortia with acetate as the predominant component. Furthermore, in the 2-bromoethanesulfonic acid-amended consortia, almost half of the original substrate carbon was metabolized to 10 monoaromatic compounds, with the most appreciable quantities accumulated as cinnamic, benzoic, caffeic, vanillic, and ferulic acids. 2-Bromoethanesulfonic acid seemed to effectively block CH4 formation in the anaerobic food chain, resulting in the observed buildup of volatile fatty acids and monoaromatic intermediates. Neither fatty acids nor aromatic compounds were detected in the oligolignol substrate before its metabolism, suggesting that these anaerobic consortia have the ability to mediate the cleavage of the β-aryl-ether bond, the most common intermonomeric linkage in lignin, with the subsequent release of the observed constituent aromatic monomers. PMID:16346722

  10. Enzymatic synthesis of enantiopure alpha- and beta-amino acids by phenylalanine aminomutase-catalysed amination of cinnamic acid derivatives.

    PubMed

    Wu, Bian; Szymanski, Wiktor; Wietzes, Piet; de Wildeman, Stefaan; Poelarends, Gerrit J; Feringa, Ben L; Janssen, Dick B

    2009-01-26

    The phenylalanine aminomutase (PAM) from Taxus chinensis catalyses the conversion of alpha-phenylalanine to beta-phenylalanine, an important step in the biosynthesis of the N-benzoyl phenylisoserinoyl side-chain of the anticancer drug taxol. Mechanistic studies on PAM have suggested that (E)-cinnamic acid is an intermediate in the mutase reaction and that it can be released from the enzyme's active site. Here we describe a novel synthetic strategy that is based on the finding that ring-substituted (E)-cinnamic acids can serve as a substrate in PAM-catalysed ammonia addition reactions for the biocatalytic production of several important beta-amino acids. The enzyme has a broad substrate range and a high enantioselectivity with cinnamic acid derivatives; this allows the synthesis of several non-natural aromatic alpha- and beta-amino acids in excellent enantiomeric excess (ee >99 %). The internal 5-methylene-3,5-dihydroimidazol-4-one (MIO) cofactor is essential for the PAM-catalysed amination reactions. The regioselectivity of amination reactions was influenced by the nature of the ring substituent.

  11. Scaleable production and separation of fermentation-derived acetic acid. Final CRADA report.

    SciTech Connect

    Snyder, S. W.; Energy Systems

    2010-02-08

    Half of U.S. acetic acid production is used in manufacturing vinyl acetate monomer (VAM) and is economical only in very large production plants. Nearly 80% of the VAM is produced by methanol carbonylation, which requires high temperatures and exotic construction materials and is energy intensive. Fermentation-derived acetic acid production allows for small-scale production at low temperatures, significantly reducing the energy requirement of the process. The goal of the project is to develop a scaleable production and separation process for fermentation-derived acetic acid. Synthesis gas (syngas) will be fermented to acetic acid, and the fermentation broth will be continuously neutralized with ammonia. The acetic acid product will be recovered from the ammonium acid broth using vapor-based membrane separation technology. The process is summarized in Figure 1. The two technical challenges to success are selecting and developing (1) microbial strains that efficiently ferment syngas to acetic acid in high salt environments and (2) membranes that efficiently separate ammonia from the acetic acid/water mixture and are stable at high enough temperature to facilitate high thermal cracking of the ammonium acetate salt. Fermentation - Microbial strains were procured from a variety of public culture collections (Table 1). Strains were incubated and grown in the presence of the ammonium acetate product and the fastest growing cultures were selected and incubated at higher product concentrations. An example of the performance of a selected culture is shown in Figure 2. Separations - Several membranes were considered. Testing was performed on a new product line produced by Sulzer Chemtech (Germany). These are tubular ceramic membranes with weak acid functionality (see Figure 3). The following results were observed: (1) The membranes were relatively fragile in a laboratory setting; (2) Thermally stable {at} 130 C in hot organic acids; (3) Acetic acid rejection > 99%; and (4

  12. EIMS Fragmentation Pathways and MRM Quantification of 7α/β-Hydroxy-Dehydroabietic Acid TMS Derivatives

    NASA Astrophysics Data System (ADS)

    Rontani, Jean-François; Aubert, Claude; Belt, Simon T.

    2015-09-01

    EI mass fragmentation pathways of TMS derivatives οf 7α/β-hydroxy-dehydroabietic acids resulting from NaBH4-reduction of oxidation products of dehydroabietic acid (a component of conifers) were investigated and deduced by a combination of (1) low energy CID-GC-MS/MS, (2) deuterium labeling, (3) different derivatization methods, and (4) GC-QTOF accurate mass measurements. Having identified the main fragmentation pathways, the TMS-derivatized 7α/β-hydroxy-dehydroabietic acids could be quantified in multiple reaction monitoring (MRM) mode in sea ice and sediment samples collected from the Arctic. These newly characterized transformation products of dehydroabietic acid constitute potential tracers of biotic and abiotic degradation of terrestrial higher plants in the environment.

  13. EIMS Fragmentation Pathways and MRM Quantification of 7α/β-Hydroxy-Dehydroabietic Acid TMS Derivatives.

    PubMed

    Rontani, Jean-François; Aubert, Claude; Belt, Simon T

    2015-09-01

    EI mass fragmentation pathways of TMS derivatives οf 7α/β-hydroxy-dehydroabietic acids resulting from NaBH(4)-reduction of oxidation products of dehydroabietic acid (a component of conifers) were investigated and deduced by a combination of (1) low energy CID-GC-MS/MS, (2) deuterium labeling, (3) different derivatization methods, and (4) GC-QTOF accurate mass measurements. Having identified the main fragmentation pathways, the TMS-derivatized 7α/β-hydroxy-dehydroabietic acids could be quantified in multiple reaction monitoring (MRM) mode in sea ice and sediment samples collected from the Arctic. These newly characterized transformation products of dehydroabietic acid constitute potential tracers of biotic and abiotic degradation of terrestrial higher plants in the environment.

  14. Recent trends in the analysis of amino acids in fruits and derived foodstuffs.

    PubMed

    Mandrioli, Roberto; Mercolini, Laura; Raggi, Maria Augusta

    2013-10-01

    The amino acid content of fruit and fruit-derived foods is studied intensely because of the contribution to nutritional value, aroma, taste and health-promoting effects and their possible use as markers of origin and authenticity. In this review, based on 101 references, the most recent trends in the analysis of amino acids are presented: the most important techniques, the different sample treatment procedures (including derivatisation) and the most frequent applications are described and compared. Pertinent publications were retrieved from Scopus and Web of Knowledge database searches lastly performed in February 2012 with the keywords "amino acid", "analysis", "liquid chromatography", "gas chromatography", "electrophoresis", "fruit", and "vegetables"; the time limit was set from the year 2000 onwards. Although amino acids have been analysed in foods for decades, new technical possibilities and advancements have allowed ever-increasing accuracy and targeting of the methods in order to overcome the challenges posed by the complex plant matrices and their high intrinsic variability.

  15. Five organic salts assembled from carboxylic acids and bis-imidazole derivatives through collective noncovalent interactions

    NASA Astrophysics Data System (ADS)

    Jin, Shouwen; Guo, Jianzhong; Liu, Li; Wang, Daqi

    2011-10-01

    Five multicomponent crystals of bis(imidazole) derivatives have been prepared with 5-nitrosalicylic acid, 5-sulfosalicylic acid, and phthalic acid. The five crystalline forms reported are organic salts of which the crystal structures have all been determined by X-ray diffraction. The results presented herein indicate that the strength and directionality of the N sbnd H⋯O, O sbnd H⋯O, and N sbnd H⋯N hydrogen bonds (ionic or neutral) between carboxylic acids and ditopic imidazoles are sufficient to bring about the formation of binary organic salts. All supramolecular architectures of the organic salts 1- 5 involve extensive O sbnd H⋯O, and N sbnd H⋯O hydrogen bonds as well as other noncovalent interactions. The role of weak and strong noncovalent interactions in the crystal packing is ascertained. These noncovalent interactions combined, all the complexes displayed 3D framework structure.

  16. The influence of the crystal structure on aggregation-induced luminescence of derivatives of aminobenzoic acid

    NASA Astrophysics Data System (ADS)

    Nosova, D. A.; Zarochentseva, E. P.; Vysotskaya, S. O.; Klemesheva, N. A.; Korotkov, V. I.

    2014-12-01

    The luminescence of three derivatives of 2-(phenylamino)-benzoic acid (N-phenylanthranilic, mefenamic, and niflumic acids) in benzene solution, in the polycrystalline state, and in the hexamethylbenzene matrix is studied. In the crystalline state, these compounds exhibit intense aggregation-induced luminescence. An increase in luminescence is also observed in the impurity crystal. The hexamethylbenzene crystal lattice restricts the mobility of molecules, thus ensuring the rigidity of the molecular structure of acids, which decreases the efficiency of nonradiative electron energy degradation. The main reason for the increase in the luminescence intensity in the case of fixation in a crystalline matrix is the formation of intramolecular hydrogen bonds and dimers of acid molecules.

  17. Two glucosylated abscisic acid derivates from avocado seeds (Persea americana Mill. Lauraceae cv. Hass).

    PubMed

    del Refugio Ramos, María; Jerz, Gerold; Villanueva, Socorro; López-Dellamary, Fernando; Waibel, Reiner; Winterhalter, Peter

    2004-04-01

    Phytochemical investigation of avocado seed material (Persea americana Mill., Lauraceae) resulted in the isolation of two glucosylated abscisic acid derivates. One of these was not known as a natural product and can be regarded as a potential 'missing link' in abscisic acid metabolism in plants. After fractionation by high-speed countercurrent chromatography, and multiple steps of column chromatography, structures were elucidated by 1D-, 2D-NMR, electrospray-MS to be the novel beta-d-glucoside of (1'S,6'R)-8'-hydroxyabscisic acid, and (1'R,3'R,5'R,8'S)-epi-dihydrophaseic acid beta-d-glucoside. Absolute configuration was determined by circulardichroism, optical rotation, and by NOE experiments.

  18. MOF-Derived Tungstated Zirconia as Strong Solid Acids toward High Catalytic Performance for Acetalization.

    PubMed

    Wang, Peng; Feng, Jian; Zhao, Yupei; Wang, Shaobin; Liu, Jian

    2016-09-14

    A strong solid acid, tungstated zirconia (WZ), has been prepared first using tungstate immobilized UiO-66 as precursors through a "double-solvent" impregnation method under mild calcination temperature. With moderate W contents, the as-synthesized WZ catalysts possess a high density of acid sites, and the proper heat treatment also has facilely led to a bunch of oligomeric tungsten clusters on stabilized tetragonal ZrO2. The resultant solid acids show an improved catalytic performance toward the benzaldehyde's acetalization in comparison with traditional zirconium hydroxide-prepared WZ. Notably, due to large surface area and additionally introduced strong acid sites, the MOF-derived WZ catalysts afforded conversion up to 86.0%. The facile method endows the WZ catalysts with superior catalytic activities and excellent recyclability, thus opening a new avenue for preparation of metal oxide-based solid superacids and superbases. PMID:27557351

  19. Targeting leukemic side population cells by isatin derivatives of nicotinic acid amide.

    PubMed

    Naglah, A M; Shinwari, Z; Bhat, M A; Al-Tahhan, M; Al-Omar, M A; Al-Dhfyan, A

    2016-01-01

    Side population (SP) cells mediate chemoresistance in leukemia. However, chemical inhibition approach to target SP cells has been poorly studied. Herein, we report the discovery of isatin derivatives of nicotinic acid amide as potent side population cell inhibitors. The selected derivatives showed superior potency over the reference drug verapamil. Furthermore, the treatment increased chemosensitivity and inhibited the cell proliferation on three different leukemic cell lines, K562, THP-1 and U937, suggesting that both SP and the bulk of leukemic cells are affected. Moreover, treatment with the most potent compound Nic9 reduced the expression of ABCG2, demonstrating that side population inhibition effect of the target derivatives is at least via ABCG2 inhibition. Importantly, the target derivatives induced erythrocyte/dendritic differentiation to leukemic cells mainly through Musashi/Numb pathway modulation. PMID:27358121

  20. Antiparasitic evaluation of betulinic acid derivatives reveals effective and selective anti-Trypanosoma cruzi inhibitors.

    PubMed

    Meira, Cássio Santana; Barbosa-Filho, José Maria; Lanfredi-Rangel, Adriana; Guimarães, Elisalva Teixeira; Moreira, Diogo Rodrigo Magalhães; Soares, Milena Botelho Pereira

    2016-07-01

    Betulinic acid is a pentacyclic triterpenoid with several biological properties already described, including antiparasitic activity. Here, the anti-Trypanosoma cruzi activity of betulinic acid and its semi-synthetic amide derivatives (BA1-BA8) was investigated. The anti-Trypanosoma cruzi activity and selectivity were enhanced in semi-synthetic derivatives, specially on derivatives BA5, BA6 and BA8. To understand the mechanism of action underlying betulinic acid anti-T. cruzi activity, we investigated ultrastructural changes by electron microscopy. Ultrastructural studies showed that trypomastigotes incubated with BA5 had membrane blebling, flagella retraction, atypical cytoplasmic vacuoles and Golgi cisternae dilatation. Flow cytometry analysis showed that parasite death is mainly caused by necrosis. Treatment with derivatives BA5, BA6 or BA8 reduced the invasion process, as well as intracellular parasite development in host cells, with a potency and selectivity similar to that observed in benznidazole-treated cells. More importantly, the combination of BA5 and benznidazole revealed synergistic effects on trypomastigote and amastigote forms of T. cruzi. In conclusion, we demonstrated that BA5 compound is an effective and selective anti-T. cruzi agent.

  1. Antiparasitic evaluation of betulinic acid derivatives reveals effective and selective anti-Trypanosoma cruzi inhibitors.

    PubMed

    Meira, Cássio Santana; Barbosa-Filho, José Maria; Lanfredi-Rangel, Adriana; Guimarães, Elisalva Teixeira; Moreira, Diogo Rodrigo Magalhães; Soares, Milena Botelho Pereira

    2016-07-01

    Betulinic acid is a pentacyclic triterpenoid with several biological properties already described, including antiparasitic activity. Here, the anti-Trypanosoma cruzi activity of betulinic acid and its semi-synthetic amide derivatives (BA1-BA8) was investigated. The anti-Trypanosoma cruzi activity and selectivity were enhanced in semi-synthetic derivatives, specially on derivatives BA5, BA6 and BA8. To understand the mechanism of action underlying betulinic acid anti-T. cruzi activity, we investigated ultrastructural changes by electron microscopy. Ultrastructural studies showed that trypomastigotes incubated with BA5 had membrane blebling, flagella retraction, atypical cytoplasmic vacuoles and Golgi cisternae dilatation. Flow cytometry analysis showed that parasite death is mainly caused by necrosis. Treatment with derivatives BA5, BA6 or BA8 reduced the invasion process, as well as intracellular parasite development in host cells, with a potency and selectivity similar to that observed in benznidazole-treated cells. More importantly, the combination of BA5 and benznidazole revealed synergistic effects on trypomastigote and amastigote forms of T. cruzi. In conclusion, we demonstrated that BA5 compound is an effective and selective anti-T. cruzi agent. PMID:27080160

  2. Carboxylic Acid Fullerene (C60) Derivatives Attenuated Neuroinflammatory Responses by Modulating Mitochondrial Dynamics

    NASA Astrophysics Data System (ADS)

    Ye, Shefang; Zhou, Tong; Cheng, Keman; Chen, Mingliang; Wang, Yange; Jiang, Yuanqin; Yang, Peiyan

    2015-05-01

    Fullerene (C60) derivatives, a unique class of compounds with potent antioxidant properties, have been reported to exert a wide variety of biological activities including neuroprotective properties. Mitochondrial dynamics are an important constituent of cellular quality control and function, and an imbalance of the dynamics eventually leads to mitochondria disruption and cell dysfunctions. This study aimed to assess the effects of carboxylic acid C60 derivatives (C60-COOH) on mitochondrial dynamics and elucidate its associated mechanisms in lipopolysaccharide (LPS)-stimulated BV-2 microglial cell model. Using a cell-based functional screening system labeled with DsRed2-mito in BV-2 cells, we showed that LPS stimulation led to excessive mitochondrial fission, increased mitochondrial localization of dynamin-related protein 1 (Drp1), both of which were markedly suppressed by C60-COOH pretreatment. LPS-induced mitochondria reactive oxygen species (ROS) generation and collapse of mitochondrial membrane potential (Δ Ψm) were also significantly inhibited by C60-COOH. Moreover, we also found that C60-COOH pretreatment resulted in the attenuation of LPS-mediated activation of nuclear factor (NF)-κB and mitogen-activated protein kinase (MAPK) signaling, as well as the production of pro-inflammatory mediators. Taken together, these findings demonstrated that carboxylic acid C60 derivatives may exert neuroprotective effects through regulating mitochondrial dynamics and functions in microglial cells, thus providing novel insights into the mechanisms of the neuroprotective properties of carboxylic acid C60 derivatives.

  3. Composition, assimilation and degradation of Phaeocystis globosa-derived fatty acids in the North Sea

    NASA Astrophysics Data System (ADS)

    Hamm, Christian E.; Rousseau, Veronique

    2003-12-01

    The fate of a Phaeocystis globosa bloom in the southern North Sea off Belgium, the Netherlands and Germany in May 1995 was investigated during a cruise with RV 'Belgica'. We used fatty acids as biomarkers to follow the fate of Phaeocystis-derived biomass of a Phaeocystis-dominated spring bloom. The bloom, in which up to >99% of the biomass was contributed by Phaeocystis, showed a fatty acid composition with a characteristically high abundance of polyunsaturated C 18-fatty acids, which increased in concentration with number of double bonds up to 18:5 (n-3), and high concentrations of 20:5 (n-3) and 22:6 (n-3). In contrast to most previous studies, fatty acid analysis of the mesozooplankton community (mainly calanoid copepods) and meroplankton ( Carcinus maenas megalope) indicated that P. globosa was a major component (ca. 70% and 50%, respectively) in the diet of these organisms. Massive accumulations of amorphous grey aggregates, in which Phaeocystis colonies were major components, were dominated by saturated fatty acids and contained only few of the polyunsaturated C 18-fatty acids. A hydrophobic surface slick that covered the water surface during the bloom showed very similar patterns. Foam patches contained few Phaeocystis-typical fatty acids, but increased amounts of diatom-typical compounds such as 16:1 (n-7) and 20:5 (n-3), and 38% fatty alcohols, indicating that wax esters dominated the lipid fraction in the foam with ca. 76% (w/w). The fatty acid compositions of surface sediment showed that no sedimentation of fresh Phaeocystis occurred during the study. The results indicate that Phaeocystis-derived organic matter degraded while floating or in suspension, and had not reached the sediment in substantial amounts.

  4. Mononuclear phagocyte accumulates a stearic acid derivative during differentiation into macrophages. Effects of stearic acid on macrophage differentiation and Mycobacterium tuberculosis control.

    PubMed

    Mosquera-Restrepo, Sergio Fabián; Caro, Ana Cecilia; Peláez-Jaramillo, Carlos Alberto; Rojas, Mauricio

    2016-05-01

    The fatty acid composition of monocytes changes substantially during differentiation into macrophages, increasing the proportion of saturated fatty acids. These changes prompted us to investigate whether fatty acid accumulation in the extracellular milieu could affect the differentiation of bystander mononuclear phagocytes. An esterified fatty acid derivative, stearate, was the only fatty acid that significantly increased in macrophage supernatants, and there were higher levels when cells differentiated in the presence of Mycobacterium tuberculosis H37Rv or purified protein derivative (PPD). Exogenous stearic acid enhanced the expression of HLA-DR and CD64; there was also accumulation of IL-12, TNF-α, IL-6, MIP-1 α and β and a reduction in MCP-1 and the bacterial load. These results suggested that during differentiation, a derivative of stearic acid, which promotes the process as well as the effector mechanisms of phagocytes against the mycobacterium, accumulates in the cell supernatants.

  5. 15-oxoeicosatetraenoic acid is a 15-hydroxyprostaglandin dehydrogenase-derived electrophilic mediator of inflammatory signaling pathways

    PubMed Central

    Snyder, Nathaniel W.; Golin-Bisello, Franca; Gao, Yang; Blair, Ian A.; Freeman, Bruce A.; Wendell, Stacy Gelhaus

    2014-01-01

    Bioactive lipids govern cellular homeostasis and pathogenic inflammatory processes. Current dogma holds that bioactive lipids, such as prostaglandins and lipoxins, are inactivated by 15-hydroxyprostaglandin dehydrogenase (15PGDH). In contrast, the present results reveal that catabolic “inactivation” of hydroxylated polyunsaturated fatty acids (PUFAs) yields electrophilic α,β-unsaturated ketone derivatives. These endogenously produced species are chemically reactive signaling mediators that induce tissue protective events. Electrophilic fatty acids diversify the proteome through post-translational alkylation of nucleophilic cysteines in key transcriptional regulatory proteins and enzymes that govern cellular metabolic and inflammatory homeostasis. 15PGDH regulates these processes as it is responsible for the formation of numerous electrophilic fatty acids including the arachidonic acid metabolite, 15-oxoeicosatetraenoic acid (15-oxoETE). Herein, the role of 15-oxoETE in regulating signaling responses is reported. In cell cultures, 15-oxoETE activates Nrf2-regulated antioxidant responses (AR) and inhibits NF-κB-mediated pro-inflammatory responses via IKKβ inhibition. Inhibition of glutathione S-transferases using ethacrynic acid incrementally increased the signaling capacity of 15-oxoETE by decreasing 15-oxoETE-GSH adduct formation. This work demonstrates that 15PGDH plays a role in the regulation of cell and tissue homeostasis via the production of electrophilic fatty acid signaling mediators. PMID:25450232

  6. Transformation of cellulose and its derived carbohydrates into formic and lactic acids catalyzed by vanadyl cations.

    PubMed

    Tang, Zhenchen; Deng, Weiping; Wang, Yanliang; Zhu, Enze; Wan, Xiaoyue; Zhang, Qinghong; Wang, Ye

    2014-06-01

    The transformation of cellulose or cellulose-derived carbohydrates into platform chemicals is the key to establish biomass-based sustainable chemical processes. The systems able to catalyze the conversion of cellulose into key chemicals in water without the consumption of hydrogen are limited. We report that simple vanadyl (VO(2+)) cations catalyze the conversions of cellulose and its monomer, glucose, into lactic acid and formic acid in water. We have discovered an interesting shift of the major product from formic acid to lactic acid on switching the reaction atmosphere from oxygen to nitrogen. Our studies suggest that VO(2+) catalyzes the isomerization of glucose to fructose, the retro-aldol fragmentation of fructose to two trioses, and the isomerization of trioses, which leads to the formation of lactic acid under anaerobic conditions. The oxidative cleavage of C-C bonds in the intermediates caused by the redox conversion of VO2(+)/VO(2+) under aerobic conditions results in formic acid and CO2. We demonstrate that the addition of an alcohol suppresses the formation of CO2 and enhances the formic acid yield significantly to 70-75 %.

  7. Interaction of cinnamic acid derivatives with β-cyclodextrin in water: experimental and molecular modeling studies.

    PubMed

    Liu, Benguo; Zeng, Jie; Chen, Chen; Liu, Yonglan; Ma, Hanjun; Mo, Haizhen; Liang, Guizhao

    2016-03-01

    Cyclodextrins (CDs) can be used to improve the solubility and stability of cinnamic acid derivatives (CAs). However, there was no detailed report about understanding the effects of the substituent groups in the benzene ring on the inclusion behavior between CAs and CDs in aqueous solution. Here, the interaction of β-CD with CAs, including caffeic acid, ferulic acid, and p-coumaric acid, in water was investigated by phase-solubility method, UV, fluorescence, and (1)H NMR spectroscopy, together with ONIOM (our Own N-layer Integrated Orbital molecular Mechanics)-based QM/MM (Quantum Mechanics/Molecular Mechanics) calculations. Experimental results demonstrated that CAs could form 1:1 stoichiometric inclusion complex with β-CD by non-covalent bonds, and that the maximum apparent stability constants were found in caffeic acid (176M(-1)) followed by p-coumaric acid (160M(-1)) and ferulic acid (133M(-1)). Moreover, our calculations reasonably illustrated the binding orientations of β-CD with CAs determined by experimental observations.

  8. Transformation of cellulose and its derived carbohydrates into formic and lactic acids catalyzed by vanadyl cations.

    PubMed

    Tang, Zhenchen; Deng, Weiping; Wang, Yanliang; Zhu, Enze; Wan, Xiaoyue; Zhang, Qinghong; Wang, Ye

    2014-06-01

    The transformation of cellulose or cellulose-derived carbohydrates into platform chemicals is the key to establish biomass-based sustainable chemical processes. The systems able to catalyze the conversion of cellulose into key chemicals in water without the consumption of hydrogen are limited. We report that simple vanadyl (VO(2+)) cations catalyze the conversions of cellulose and its monomer, glucose, into lactic acid and formic acid in water. We have discovered an interesting shift of the major product from formic acid to lactic acid on switching the reaction atmosphere from oxygen to nitrogen. Our studies suggest that VO(2+) catalyzes the isomerization of glucose to fructose, the retro-aldol fragmentation of fructose to two trioses, and the isomerization of trioses, which leads to the formation of lactic acid under anaerobic conditions. The oxidative cleavage of C-C bonds in the intermediates caused by the redox conversion of VO2(+)/VO(2+) under aerobic conditions results in formic acid and CO2. We demonstrate that the addition of an alcohol suppresses the formation of CO2 and enhances the formic acid yield significantly to 70-75 %. PMID:24798653

  9. Highly efficient production of D-lactic acid from chicory-derived inulin by Lactobacillus bulgaricus.

    PubMed

    Xu, Qianqian; Zang, Ying; Zhou, Jie; Liu, Peng; Li, Xin; Yong, Qiang; Ouyang, Jia

    2016-11-01

    Inulin is a readily available feedstock for cost-effective production of biochemicals. To date, several studies have explored the production of bioethanol, high-fructose syrup and fructooligosaccharide, but there are no studies regarding the production of D-lactic acid using inulin as a carbon source. In the present study, chicory-derived inulin was used for D-lactic acid biosynthesis by Lactobacillus bulgaricus CGMCC 1.6970. Compared with separate hydrolysis and fermentation processes, simultaneous saccharification and fermentation (SSF) has demonstrated the best performance of D-lactic acid production. Because it prevents fructose inhibition and promotes the complete hydrolysis of inulin, the highest D-lactic acid concentration (123.6 ± 0.9 g/L) with a yield of 97.9 % was obtained from 120 g/L inulin by SSF. Moreover, SSF by L. bulgaricus CGMCC 1.6970 offered another distinct advantage with respect to the higher optical purity of D-lactic acid (>99.9 %) and reduced number of residual sugars. The excellent performance of D-lactic acid production from inulin by SSF represents a high-yield method for D-lactic acid production from non-food grains.

  10. Highly efficient production of D-lactic acid from chicory-derived inulin by Lactobacillus bulgaricus.

    PubMed

    Xu, Qianqian; Zang, Ying; Zhou, Jie; Liu, Peng; Li, Xin; Yong, Qiang; Ouyang, Jia

    2016-11-01

    Inulin is a readily available feedstock for cost-effective production of biochemicals. To date, several studies have explored the production of bioethanol, high-fructose syrup and fructooligosaccharide, but there are no studies regarding the production of D-lactic acid using inulin as a carbon source. In the present study, chicory-derived inulin was used for D-lactic acid biosynthesis by Lactobacillus bulgaricus CGMCC 1.6970. Compared with separate hydrolysis and fermentation processes, simultaneous saccharification and fermentation (SSF) has demonstrated the best performance of D-lactic acid production. Because it prevents fructose inhibition and promotes the complete hydrolysis of inulin, the highest D-lactic acid concentration (123.6 ± 0.9 g/L) with a yield of 97.9 % was obtained from 120 g/L inulin by SSF. Moreover, SSF by L. bulgaricus CGMCC 1.6970 offered another distinct advantage with respect to the higher optical purity of D-lactic acid (>99.9 %) and reduced number of residual sugars. The excellent performance of D-lactic acid production from inulin by SSF represents a high-yield method for D-lactic acid production from non-food grains. PMID:27440161

  11. Comparison of inhibition effects of some benzoic acid derivatives on sheep heart carbonic anhydrase

    NASA Astrophysics Data System (ADS)

    Kiliç, Deryanur; Yildiz, Melike; Şentürk, Murat; Erdoǧan, Orhan; Küfrevioǧlu, Ömer Irfan

    2016-04-01

    Carbonic anhydrase (CA) is a family of metalloenzymes that requires Zn as a cofactor and catalyze the quick conversion of CO2 to HCO3- and H+. Inhibitors of the carbonic anhydrases (CAs) have medical usage of significant diseases such as glaucoma, epilepsy, gastroduodenal ulcers, acid-base disequilibria and neurological disorders. In the present study, inhibition of CA with some benzoic derivatives (1-6) were investigated. Sheep heart CA (shCA) enzyme was isolated by means of designed affinity chromatography gel (cellulose-benzyl-sulfanylamide) 42.45-fold in a yield of 44 % with 564.65 EU/mg. Purified shCA enzyme was used in vitro studies. In the studies, IC50 values were calculated for 3-aminobenzoic acid (1), 4-aminobenzoic acid (2), 2-hydroxybenzoic acid (3), 2-benzoylbenzoic acid (4), 2,3-dimethoxybenzoic acid (5), and 3,4,5-trimethoxybenzoic acid (6), showing the inhibition effects on the purified enzyme. Such molecules can be used as pioneer for discovery of novel effective CA inhibitors for medicinal chemistry applications.

  12. Improving surface functional properties of tofu whey-derived peptides by chemical modification with fatty acids.

    PubMed

    Matemu, Athanasia Oswald; Katayama, Shigeru; Kayahara, Hisataka; Murasawa, Hisashi; Nakamura, Soichiro

    2012-04-01

    Effect of acylation with saturated fatty acids on surface functional properties of tofu whey-derived peptides was investigated. Tofu whey (TW) and soy proteins (7S, 11S, and acid-precipitated soy protein [APP]) were hydrolyzed by Protease M 'Amano' G, and resulting peptide mixtures were acylated with esterified fatty acids of different chain length (6C to 18C) to form a covalent linkage between the carboxyl group of fatty acid and the free amino groups of peptide. Acylation significantly (P < 0.05) increased emulsifying properties of 7S, 11S, and APP peptides independent of fatty acid chain length. Acylation decreased water binding capacity although oil binding capacity of acylated tofu whey ultra filtered fraction (UFTW < 3 kDa), 7S- and 11S-peptides were improved compared to native peptides. 7S peptides acylated with long chain fatty acids had shown significant higher surface hydrophobicity as in contrast with acylated UFTW < 3 kDa and APP peptides. Fluorescence spectra studies revealed structural conformation of acylated soy peptides as compared to native peptides. This study shows that chemical modification with fatty acids can further affect functional properties of soy proteins.

  13. D-Lactic acid biosynthesis from biomass-derived sugars via Lactobacillus delbrueckii fermentation.

    PubMed

    Zhang, Yixing; Vadlani, Praveen V

    2013-12-01

    Poly-lactic acid (PLA) derived from renewable resources is considered to be a good substitute for petroleum-based plastics. The number of poly L-lactic acid applications is increased by the introduction of a stereocomplex PLA, which consists of both poly-L and D-lactic acid and has a higher melting temperature. To date, several studies have explored the production of L-lactic acid, but information on biosynthesis of D-lactic acid is limited. Pulp and corn stover are abundant, renewable lignocellulosic materials that can be hydrolyzed to sugars and used in biosynthesis of D-lactic acid. In our study, saccharification of pulp and corn stover was done by cellulase CTec2 and sugars generated from hydrolysis were converted to D-lactic acid by a homofermentative strain, L. delbrueckii, through a sequential hydrolysis and fermentation process (SHF) and a simultaneous saccharification and fermentation process (SSF). 36.3 g L(-1) of D-lactic acid with 99.8 % optical purity was obtained in the batch fermentation of pulp and attained highest yield and productivity of 0.83 g g(-1) and 1.01 g L(-1) h(-1), respectively. Luedeking-Piret model described the mixed growth-associated production of D-lactic acid with a maximum specific growth rate 0.2 h(-1) and product formation rate 0.026 h(-1), obtained for this strain. The efficient synthesis of D-lactic acid having high optical purity and melting point will lead to unique stereocomplex PLA with innovative applications in polymer industry.

  14. Subcellular Compartmentation of the Diterpene Carnosic Acid and Its Derivatives in the Leaves of Rosemary1

    PubMed Central

    Munné-Bosch, Sergi; Alegre, Leonor

    2001-01-01

    The potent antioxidant properties of rosemary (Rosmarinus officinalis) extracts have been attributed to its major diterpene, carnosic acid. Carnosic acid has received considerable attention in food science and biomedicine, but little is known about its function in the plant in vivo. We recently found that highly oxidized diterpenes increase in rosemary plants exposed to drought and high light stress as a result of the antioxidant activity of carnosic acid (S. Munné-Bosch, K. Schwarz, L. Alegre [1999] Plant Physiol 121: 1047–1052). To elucidate the significance of the antioxidant function of carnosic acid in vivo we measured the relative amounts of carnosic acid and its metabolites in different compartments of rosemary leaves. Subcellular localization studies show that carnosic acid protects chloroplasts from oxidative stress in vivo by following a highly regulated compartmentation of oxidation products. Carnosic acid scavenges free radicals within the chloroplasts, giving rise to diterpene alcohols, mainly isorosmanol. This oxidation product is O-methylated within the chloroplasts, and the resulting form, 11,12-di-O-methylisorosmanol, is transferred to the plasma membrane. This appears to represent a mechanism of a way out for free radicals from chloroplasts. Carnosic acid also undergoes direct O-methylation within the chloroplasts, and its derived product, 12-O-methylcarnosic acid, accumulates in the plasma membrane. O-methylated diterpenes do not display antioxidant activity, but they may influence the stability of the plasma membrane. This study shows the relevance of the compartmentation of carnosic acid metabolism to the protection of rosemary plants from oxidative stress in vivo. PMID:11161064

  15. Chemistry and pharmacological action of caffeoylquinic acid derivatives and pharmaceutical utilization of chwinamul (Korean Mountainous vegetable).

    PubMed

    Park, Hee-Juhn

    2010-11-01

    Chwinamul is a mountainous vegetable that refers to several species belonging to the family Compositae. Chwinamul has been used as a side dish or a medicinal herb to treat hypercholesterolemia, diabetes, common cold, atherosclerosis, and cardiovascular disease. Caffeoylquinic acids (CQs) are present in high levels in chwinamul, though caffeoyltartaric acids (CTs) are often occurred in the vegetables of Compositae. Here I review the chemical and pharmaceutical aspects of CQs and CTs. In particular, ¹³C-NMR data and CQ stereochemistry are discussed. CQ derivatives have antioxidative, peroxynitrite-scavenging, hepatoprotective, antiviral, antiobese, and antidiabetic activities.

  16. Potential antibacterial activity of coumarin and coumarin-3-acetic acid derivatives.

    PubMed

    Chattha, Fauzia Anjum; Munawar, Munawar Ali; Nisa, Mehrun; Ashraf, Mohammad; Kousar, Samina; Arshad, Shafia

    2015-05-01

    Coumarin and coumarin-3-acetic acid derivatives were synthesized by reacting phenols with malic acid, ethyl acetoacetate and ethyl acetylsuccinate in appropriate reaction conditions. All synthesized compounds were subjected to test for their antimicrobial activities against variety of gram positive (Bacillus subtilis, Staphylococcus aureus) and gram negative bacterial stains (Shigella sonnei, Escherichia coli) by agar dilution method. Several of them exhibited appreciable good antibacterial activity against the different strains of gram positive and gram negative bacteria. These findings suggest a great potential of these compounds for screening and use as antibacterial agents for further studies with a battery of bacteria.

  17. Stability of vitamin C derivatives in topical formulations containing lipoic acid, vitamins A and E.

    PubMed

    Segall, A I; Moyano, M A

    2008-12-01

    The stability of ascorbyl palmitate, sodium ascorbyl phosphate and magnesium ascorbyl phosphate in topical formulations was investigated by direct reverse phase high performance liquid chromatography after sample dilution with a suitable buffer - organic solvent mixture. Ascorbyl palmitate, sodium ascorbyl phosphate and magnesium ascorbyl phosphate are derivatives of ascorbic acid which differ in hydrolipophilic properties. They are widely used in cosmetic and pharmaceutical preparations. According to the results, ascorbyl esters showed significant differences: sodium ascorbyl phosphate and magnesium ascorbyl phosphate are more stable derivatives of vitamin C than ascorbyl palmitate and may be easily used in cosmetic products.

  18. Separation of D-lysergic acid diethylamide derivatives using micellar electrokinetic capillary chromatography.

    PubMed

    Djordjevic, M N; Fitzpatrick, F; Houdiere, F

    2000-03-01

    By adjusting column temperature and applied electric field, a fast separation in micellar electrokinetic capillary chromatography was developed for the separation of D-lysergic acid diethylamide derivatives. A baseline separation of nine derivatives was accomplished with a run time of less than 12 min by utilizing elevated column temperature (60 degrees C) and an applied electric field of 387 V/cm. The number of plates generated per unit time for the separations completed at elevated temperatures was significantly higher when compared to separations at the same applied electric field but at lower temperatures (20 degrees C).

  19. Design, synthesis and biological activity of phenoxyacetic acid derivatives as novel free fatty acid receptor 1 agonists.

    PubMed

    Li, Zheng; Wang, Xuekun; Xu, Xue; Yang, Jianyong; Xia, Wenting; Zhou, Xianhao; Huang, Wenlong; Qian, Hai

    2015-11-15

    The free fatty acid receptor 1 (FFA1) is a novel antidiabetic target for the treatment of type 2 diabetes based on particular mechanism in amplifying glucose-stimulated insulin secretion. We have previously identified a series of phenoxyacetic acid derivatives. Herein, we describe the further chemical modification of this series directed by ligand efficiency and ligand lipophilicity efficiency. All of these efforts lead to the discovery of the promising candidate 16, an excellent FFA1 agonist with robust agonistic activity (43.6 nM), desired LE and LLE values. Moreover, compound 16 revealed a great potential for improving the hyperglycemia levels in both normal and type 2 diabetic mice without the risk of hypoglycemia even at the high dose of 40 mg/kg. PMID:26482570

  20. Biosynthesis, biological effects, and receptors of hydroxyeicosatetraenoic acids (HETEs) and oxoeicosatetraenoic acids (oxo-ETEs) derived from arachidonic acid.

    PubMed

    Powell, William S; Rokach, Joshua

    2015-04-01

    Arachidonic acid can be oxygenated by a variety of different enzymes, including lipoxygenases, cyclooxygenases, and cytochrome P450s, and can be converted to a complex mixture of oxygenated products as a result of lipid peroxidation. The initial products in these reactions are hydroperoxyeicosatetraenoic acids (HpETEs) and hydroxyeicosatetraenoic acids (HETEs). Oxoeicosatetraenoic acids (oxo-ETEs) can be formed by the actions of various dehydrogenases on HETEs or by dehydration of HpETEs. Although a large number of different HETEs and oxo-ETEs have been identified, this review will focus principally on 5-oxo-ETE, 5S-HETE, 12S-HETE, and 15S-HETE. Other related arachidonic acid metabolites will also be discussed in less detail. 5-Oxo-ETE is synthesized by oxidation of the 5-lipoxygenase product 5S-HETE by the selective enzyme, 5-hydroxyeicosanoid dehydrogenase. It actions are mediated by the selective OXE receptor, which is highly expressed on eosinophils, suggesting that it may be important in eosinophilic diseases such as asthma. 5-Oxo-ETE also appears to stimulate tumor cell proliferation and may also be involved in cancer. Highly selective and potent OXE receptor antagonists have recently become available and could help to clarify its pathophysiological role. The 12-lipoxygenase product 12S-HETE acts by the GPR31 receptor and promotes tumor cell proliferation and metastasis and could therefore be a promising target in cancer therapy. It may also be involved as a proinflammatory mediator in diabetes. In contrast, 15S-HETE may have a protective effect in cancer. In addition to GPCRs, higher concentration of HETEs and oxo-ETEs can activate peroxisome proliferator-activated receptors (PPARs) and could potentially regulate a variety of processes by this mechanism. This article is part of a Special Issue entitled "Oxygenated metabolism of PUFA: analysis and biological relevance".

  1. Structure-dependent effects of pyridine derivatives on mechanisms of intestinal fatty acid uptake: regulation of nicotinic acid receptor and fatty acid transporter expression.

    PubMed

    Riedel, Annett; Lang, Roman; Rohm, Barbara; Rubach, Malte; Hofmann, Thomas; Somoza, Veronika

    2014-07-01

    Pyridines are widely distributed in foods. Nicotinic acid (NA), a carboxylated pyridine derivative, inhibits lipolysis in adipocytes by activation of the orphan NA receptor (HM74A) and is applied to treat hyperlipidemia. However, knowledge on the impact of pyridine derivatives on intestinal lipid metabolism is scarce. This study was performed to identify the structural determinants of pyridines for their effects on fatty acid uptake in enterocyte-like Caco-2 cells and to elucidate the mechanisms of action. The impact of 17 pyridine derivatives on fatty acid uptake was tested. Multiple regression analysis revealed the presence of a methyl group to be the structural determinant at 0.1 mM, whereas at 1 mM, the presence of a carboxylic group and the N-methylation presented further structural characteristics to affect the fatty acid uptake. NA, showing a stimulating effect on FA uptake, and N-methyl-4-phenylpyridinium (MPP), inhibiting FA uptake, were selected for mechanistic studies. Gene expression of the fatty acid transporters CD36, FATP2 and FATP4, and the lipid metabolism regulating transcription factors peroxisome proliferator-activated receptor (PPAR) α and PPARγ was up-regulated upon NA treatment. Caco-2 cells were demonstrated to express the low-affinity NA receptor HM74 of which the gene expression was up-regulated upon NA treatment. We hypothesize that the NA-induced fatty acid uptake might result from NA receptor activation and related intracellular signaling cascades. In contrast, MPP increased transepithelial electrical resistance. We therefore conclude that NA and MPP, both sharing the pyridine motif core, exhibit their contrary effects on intestinal FA uptake by activation of different mechanisms.

  2. Structure-dependent effects of pyridine derivatives on mechanisms of intestinal fatty acid uptake: regulation of nicotinic acid receptor and fatty acid transporter expression.

    PubMed

    Riedel, Annett; Lang, Roman; Rohm, Barbara; Rubach, Malte; Hofmann, Thomas; Somoza, Veronika

    2014-07-01

    Pyridines are widely distributed in foods. Nicotinic acid (NA), a carboxylated pyridine derivative, inhibits lipolysis in adipocytes by activation of the orphan NA receptor (HM74A) and is applied to treat hyperlipidemia. However, knowledge on the impact of pyridine derivatives on intestinal lipid metabolism is scarce. This study was performed to identify the structural determinants of pyridines for their effects on fatty acid uptake in enterocyte-like Caco-2 cells and to elucidate the mechanisms of action. The impact of 17 pyridine derivatives on fatty acid uptake was tested. Multiple regression analysis revealed the presence of a methyl group to be the structural determinant at 0.1 mM, whereas at 1 mM, the presence of a carboxylic group and the N-methylation presented further structural characteristics to affect the fatty acid uptake. NA, showing a stimulating effect on FA uptake, and N-methyl-4-phenylpyridinium (MPP), inhibiting FA uptake, were selected for mechanistic studies. Gene expression of the fatty acid transporters CD36, FATP2 and FATP4, and the lipid metabolism regulating transcription factors peroxisome proliferator-activated receptor (PPAR) α and PPARγ was up-regulated upon NA treatment. Caco-2 cells were demonstrated to express the low-affinity NA receptor HM74 of which the gene expression was up-regulated upon NA treatment. We hypothesize that the NA-induced fatty acid uptake might result from NA receptor activation and related intracellular signaling cascades. In contrast, MPP increased transepithelial electrical resistance. We therefore conclude that NA and MPP, both sharing the pyridine motif core, exhibit their contrary effects on intestinal FA uptake by activation of different mechanisms. PMID:24767308

  3. Transition-Metal-Free ipso-Functionalization of Arylboronic Acids and Derivatives

    PubMed Central

    Zhu, Chen; Falck, John R.

    2014-01-01

    Arylboronic acids and their derivatives have been widely exploited as important synthetic precursors in organic synthesis, materials science, and pharmaceutical development. In addition to numerous applications in transition-metal-mediated cross-coupling reactions, transition-metal-free transformations involving arylboronic acids and derivatives have recently received a surge of attention for converting the C-B bond to C-C, C-N, C-O, and many other C-X bonds. Consequently, a wide range of useful compounds, e.g., phenols, anilines, nitroarenes, and haloarenes, have been readily synthesized. Amongst these efforts, many versatile reagents have been developed and a lot of practical approaches demonstrated. The research in this promising field is summarized in the current review and organized on the basis of the type of bonds being formed. PMID:25414624

  4. Synthesis, characterisation and antioxidant features of procyanidin B4 and malvidin-3-glucoside stearic acid derivatives.

    PubMed

    Cruz, Luis; Fernandes, Virgínia C; Araújo, Paula; Mateus, Nuno; de Freitas, Victor

    2015-05-01

    The acylation of procyanidin B4 with a saturated fatty acid chloride containing 18 carbon atoms was studied in order to obtain procyanidin B4 3-O-di-stearic acid conjugate. This compound was structurally characterised by mass spectrometry and 1D and 2D NMR techniques. Derivatization of malvidin-3-glucoside using stearoyl chloride in acetonitrile was also performed yielding mono-, di- and tri-stearic ester derivatives. The novel derivatives obtained revealed significant antioxidant activity, although lower than the respective precursors. However, the chemical modification of anthocyanins and procyanidins (water soluble pigments) to more lipophilic compounds has the advantage of increased bioavailability in biological matrices, and to potentiate their application in food matrices and cosmetic products.

  5. Synthesis and Pro-Apoptotic Activity of Novel Glycyrrhetinic Acid Derivatives

    PubMed Central

    Logashenko, Evgeniya B; Salomatina, Oksana V; Markov, A V; Korchagina, Dina V; Salakhutdinov, Nariman F; Tolstikov, Genrikh A; Vlassov, Valentin V; Zenkova, Marina A

    2011-01-01

    Triterpenoids are used for medicinal purposes in many countries. Some, such as oleanolic and glycyrrhetinic acids, are known to be anti-inflammatory and anticarcinogenic. However, the biological activities of these naturally occurring molecules against their particular targets are weak, so the synthesis of new synthetic analogues with enhanced potency is needed. By combining modifications to both the A and C rings of 18βH-glycyrrhetinic acid, the novel synthetic derivative methyl 2-cyano-3,12-dioxo-18βH-olean-9(11),1(2)-dien-30-oate was obtained. This derivative displays high antiproliferative activity in cancer cells, including a cell line with a multidrug-resistance phenotype. It causes cell death by inducing the intrinsic caspase-dependent apoptotic pathway. PMID:21328513

  6. Supramolecular chiral host-guest nanoarchitecture induced by the selective assembly of barbituric acid derivative enantiomers.

    PubMed

    Sun, Xiaonan; Silly, Fabien; Maurel, Francois; Dong, Changzhi

    2016-10-21

    Barbituric acid derivatives are prochiral molecules, i.e. they are chiral upon adsorption on surfaces. Scanning tunneling microscopy reveals that barbituric acid derivatives self-assemble into a chiral guest-host supramolecular architecture at the solid-liquid interface on graphite. The host nanoarchitecture has a sophisticated wavy shape pattern and paired guest molecules are nested insides the cavities of the host structure. Each unit cell of the host structure is composed of both enantiomers with a ratio of 1:1. Furthermore, the wavy patterns of the nanoarchitecture are formed from alternative appearance of left- and right-handed chiral building blocks, which makes the network heterochiral. The functional guest-host nanoarchitecture is the result of two-dimensional chiral amplification from single enantiomers to organizational heterochiral supramolecular self-assembly. PMID:27623155

  7. Supramolecular chiral host-guest nanoarchitecture induced by the selective assembly of barbituric acid derivative enantiomers

    NASA Astrophysics Data System (ADS)

    Sun, Xiaonan; Silly, Fabien; Maurel, Francois; Dong, Changzhi

    2016-10-01

    Barbituric acid derivatives are prochiral molecules, i.e. they are chiral upon adsorption on surfaces. Scanning tunneling microscopy reveals that barbituric acid derivatives self-assemble into a chiral guest-host supramolecular architecture at the solid-liquid interface on graphite. The host nanoarchitecture has a sophisticated wavy shape pattern and paired guest molecules are nested insides the cavities of the host structure. Each unit cell of the host structure is composed of both enantiomers with a ratio of 1:1. Furthermore, the wavy patterns of the nanoarchitecture are formed from alternative appearance of left- and right-handed chiral building blocks, which makes the network heterochiral. The functional guest-host nanoarchitecture is the result of two-dimensional chiral amplification from single enantiomers to organizational heterochiral supramolecular self-assembly.

  8. Stereoselective Synthesis of α-Amino-C-phosphinic Acids and Derivatives.

    PubMed

    Viveros-Ceballos, José Luis; Ordóñez, Mario; Sayago, Francisco J; Cativiela, Carlos

    2016-01-01

    α-Amino-C-phosphinic acids and derivatives are an important group of compounds of synthetic and medicinal interest and particular attention has been dedicated to their stereoselective synthesis in recent years. Among these, phosphinic pseudopeptides have acquired pharmacological importance in influencing physiologic and pathologic processes, primarily acting as inhibitors for proteolytic enzymes where molecular stereochemistry has proven to be critical. This review summarizes the latest developments in the asymmetric synthesis of acyclic and phosphacyclic α-amino-C-phosphinic acids and derivatives, following in the first case an order according to the strategy used, whereas for cyclic compounds the nitrogen embedding in the heterocyclic core is considered. In addition selected examples of pharmacological implications of title compounds are also disclosed. PMID:27589703

  9. Hydroxycinnamic acid derivatives: a potential class of natural compounds for the management of lipid metabolism and obesity.

    PubMed

    Alam, Md Ashraful; Subhan, Nusrat; Hossain, Hemayet; Hossain, Murad; Reza, Hasan Mahmud; Rahman, Md Mahbubur; Ullah, M Obayed

    2016-01-01

    Hydroxycinnamic acid derivatives are important class of polyphenolic compounds originated from the Mavolanate-Shikimate biosynthesis pathways in plants. Several simple phenolic compounds such as cinnamic acid, p-coumaric acid, ferulic acid, caffeic acid, chlorgenic acid, and rosmarinic acid belong to this class. These phenolic compounds possess potent antioxidant and anti-inflammatory properties. These compounds were also showed potential therapeutic benefit in experimental diabetes and hyperlipidemia. Recent evidences also suggest that they may serve as valuable molecule for the treatment of obesity related health complications. In adipose tissues, hydroxycinnamic acid derivatives inhibit macrophage infiltration and nuclear factor κB (NF-κB) activation in obese animals. Hydroxycinnamic acid derivatives also reduce the expression of the potent proinflammatory adipokines tumor necrosis factor-α (TNFα), monocyte chemoattractant protein-1 (MCP-1), and plasminogen activator inhibitor type-1 (PAI-1), and they increase the secretion of an anti-inflammatory agent adiponectin from adipocytes. Furthermore, hydroxycinnamic acid derivatives also prevent adipocyte differentiation and lower lipid profile in experimental animals. Through these diverse mechanisms hydroxycinnamic acid derivatives reduce obesity and curtail associated adverse health complications.

  10. HPLC quantification of all five ginkgolic acid derivatives in Ginkgo biloba extracts using 13 : 0 ginkgolic acid as a single marker compound.

    PubMed

    Wang, Ruwei; Kobayashi, Yuta; Lin, Yu; Rauwald, Hans Wilhelm; Yao, Jianbiao; Fang, Ling; Qiao, Hongxiang; Kuchta, Kenny

    2015-01-01

    An HPLC quantification method for ginkgolic acid derivatives in Ginkgo biloba leaf extracts was developed. Using 13 : 0 ginkgolic acid as a marker compound, the relative correlation factors of the four other ginkgolic acid derivatives - namely, 15 : 0 ginkgolic acid, 15 : 1 ginkgolic acid, 17 : 1 ginkgolic acid, and 17 : 2 ginkgolic acid - to 13 : 0 ginkgolic acid were determined by HPLC and subsequently used for calculating their contents in ten hydro-ethanolic refined extract samples. In other words, the content of 13 : 0 ginkgolic acid in the extracts was determined using the isolated compound as an external standard. Subsequently the now known concentration of this compound functioned as an internal standard for the quantification of the other four ginkgolic acid derivatives via the described correlation factors. This HPLC method was validated by two independent control measurements, one with an external standard for every individual compound and one based on the present method with the single marker compound alone. The results did not differ significantly in any of the 10 tested extract samples. The protocol presented here thus not only uses the same reference substance for G. biloba extracts as the current Chinese Pharmacopoeia method but also incorporates the advantages of the current European Pharmacopoeia approach. It is simple, reproducible, and can be used to determine the total contents of ginkgolic acid derivatives in G. biloba leaf extracts. PMID:25519835

  11. Synthesis of sulfonic acid derivatives by oxidative deprotection of thiols using tert-butyl hypochlorite.

    PubMed

    Joyard, Yoann; Papamicaël, Cyril; Bohn, Pierre; Bischoff, Laurent

    2013-05-01

    Starting from alkyl halides or Michael acceptors, thioacetates were prepared in situ and further treated with t-BuOCl, affording the corresponding sulfonyl chlorides which were trapped with nucleophiles such as water, alcohol, or amines. The three steps can be achieved in a one-pot procedure. Oxidative deprotection also proved to be efficient with S-trityl and S-tert-butyl groups, making it a convenient route toward cysteic acid derivatives.

  12. Synthesis and evaluation of aminophosphinic acid derivatives as inhibitors of renal dipeptidase.

    PubMed

    Gurulingappa, Hallur; Buckhalts, Phillip; Kinzler, Kenneth W; Vogelstein, Bert; Khan, Saeed R

    2004-07-01

    Renal dipeptidase (RDP) is an enzyme overexpressed in benign and malignant colorectal tumors. In an effort to identify potent inhibitors of this enzyme, a series of aminophosphinic acid derivatives were synthesized. Compounds 3a and 3c in which the phenyl ring was para substituted with F and Br and olefin with Z geometry, showed better inhibitory activity against RDP enzyme (IC50 = 5-6 nM).

  13. Application of derivative UV spectrophotometry for the determination of enoxacin and nalidixic acid in tablets.

    PubMed

    Hopkała, H; Kowalczuk, D

    2000-06-01

    First-, second-, third- and forth-order derivative spectrophotometric methods, using "peak-zero" (P-O) and "peak-peak" (P-P) techniques of measurement have been developed for the determination of enoxacin and nalidixic acid in tablets. The calibration curves were linear in the concentration range of 2.0-12.0 micrograms ml-1 for the analysed quinolones. The procedure was simple, rapid and the results were reliable.

  14. Lipophilic caffeic and ferulic acid derivatives presenting cytotoxicity against human breast cancer cells.

    PubMed

    Serafim, Teresa L; Carvalho, Filipa S; Marques, Maria P M; Calheiros, Rita; Silva, Tiago; Garrido, Jorge; Milhazes, Nuno; Borges, Fernanda; Roleira, Fernanda; Silva, Elisiaario T; Holy, Jon; Oliveira, Paulo J

    2011-05-16

    In the present work, lipophilic caffeic and ferulic acid derivatives were synthesized, and their cytotoxicity on cultured breast cancer cells was compared. A total of six compounds were initially evaluated: caffeic acid (CA), hexyl caffeate (HC), caffeoylhexylamide (HCA), ferulic acid (FA), hexyl ferulate (HF), and feruloylhexylamide (HFA). Cell proliferation, cell cycle progression, and apoptotic signaling were investigated in three human breast cancer cell lines, including estrogen-sensitive (MCF-7) and insensitive (MDA-MB-231 and HS578T). Furthermore, direct mitochondrial effects of parent and modified compounds were investigated by using isolated liver mitochondria. The results indicated that although the parent compounds presented no cytotoxicity, the new compounds inhibited cell proliferation and induced cell cycle alterations and cell death, with a predominant effect on MCF-7 cells. Interestingly, cell cycle data indicates that effects on nontumor BJ fibroblasts were predominantly cytostatic and not cytotoxic. The parent compounds and derivatives also promoted direct alterations on hepatic mitochondrial bioenergetics, although the most unexpected and never before reported one was that FA induces the mitochondrial permeability transition. The results show that the new caffeic and ferulic acid lipophilic derivatives show increased cytotoxicity toward human breast cancer cell lines, although the magnitude and type of effects appear to be dependent on the cell type. Mitochondrial data had no direct correspondence with effects on intact cells suggesting that this organelle may not be a critical component of the cellular effects observed. The data provide a rational approach to the design of effective cytotoxic lipophilic hydroxycinnamic derivatives that in the future could be profitably applied for chemopreventive and/or chemotherapeutic purposes.

  15. Heterogeneous and homogeneous catalysis for the hydrogenation of carboxylic acid derivatives: history, advances and future directions.

    PubMed

    Pritchard, James; Filonenko, Georgy A; van Putten, Robbert; Hensen, Emiel J M; Pidko, Evgeny A

    2015-06-01

    The catalytic reduction of carboxylic acid derivatives has witnessed a rapid development in recent years. These reactions, involving molecular hydrogen as the reducing agent, can be promoted by heterogeneous and homogeneous catalysts. The milestone achievements and recent results by both approaches are discussed in this Review. In particular, we focus on the mechanistic aspects of the catalytic hydrogenation and highlight the bifunctional nature of the mechanism that is preferred for supported metal catalysts as well as homogeneous transition metal complexes.

  16. Electrochemical Biosensors Based on Ferroceneboronic Acid and Its Derivatives: A Review

    PubMed Central

    Wang, Baozhen; Takahashi, Shigehiro; Du, Xiaoyan; Anzai, Jun-ichi

    2014-01-01

    We review recent progress in the development of electrochemical biosensors based on ferroceneboronic acid (FcBA) and ferrocene (Fc)-modified boronic acids. These compounds can be used to construct electrochemical biosensors because they consist of a binding site (i.e., a boronic acid moiety) and an electrochemically active part (i.e., an Fc residue). By taking advantage of the unique properties of FcBA and its derivatives, electrochemical sensors sensitive to sugars, glycated hemoglobin (HbA1c), fluoride (F−) ions, and so forth have been widely studied. FcBA-based sugar sensors rely on the selective binding of FcBA to 1,2- or 1,3-diol residues of sugars through the formation of cyclic boronate ester bonds. The redox properties of FcBA-sugar adduct differ from those of free FcBA, which forms the basis of the electrochemical determination of sugars. Thus, non-enzymatic glucose sensors are now being actively studied using FcBA and Fc-modified boronic acids as redox markers. Using a similar principle, HbA1c can be detected by FcBA-based electrochemical systems because it contains hydrocarbon chains on the polypeptide chain. HbA1c sensors are useful for monitoring blood glucose levels over the preceding 8–12 weeks. In addition, FcBA and Fc-modified boronic acids have been used for the detection of F− ions due to the selective binding of boronic acid to F− ions. F−-ion sensors may be useful alternatives to conventional ion-selective electrodes sensitive to F− ion. Furthermore, FcBA derivatives have been studied to construct lectin; steroids; nucleotides; salicylic acid; and bacteria sensors. One of the limitations of FcBA-based sensors comes from the fact that FcBA derivatives are added in sample solutions as reagents. FcBA derivatives should be immobilized on the surface of electrodes for developing reagentless sensors. PMID:25587421

  17. Electrochemical biosensors based on ferroceneboronic Acid and its derivatives: a review.

    PubMed

    Wang, Baozhen; Takahashi, Shigehiro; Du, Xiaoyan; Anzai, Jun-Ichi

    2014-09-01

    We review recent progress in the development of electrochemical biosensors based on ferroceneboronic acid (FcBA) and ferrocene (Fc)-modified boronic acids. These compounds can be used to construct electrochemical biosensors because they consist of a binding site (i.e., a boronic acid moiety) and an electrochemically active part (i.e., an Fc residue). By taking advantage of the unique properties of FcBA and its derivatives, electrochemical sensors sensitive to sugars, glycated hemoglobin (HbA1c), fluoride (F(-)) ions, and so forth have been widely studied. FcBA-based sugar sensors rely on the selective binding of FcBA to 1,2- or 1,3-diol residues of sugars through the formation of cyclic boronate ester bonds. The redox properties of FcBA-sugar adduct differ from those of free FcBA, which forms the basis of the electrochemical determination of sugars. Thus, non-enzymatic glucose sensors are now being actively studied using FcBA and Fc-modified boronic acids as redox markers. Using a similar principle, HbA1c can be detected by FcBA-based electrochemical systems because it contains hydrocarbon chains on the polypeptide chain. HbA1c sensors are useful for monitoring blood glucose levels over the preceding 8-12 weeks. In addition, FcBA and Fc-modified boronic acids have been used for the detection of F(-) ions due to the selective binding of boronic acid to F(-) ions. F(-)-ion sensors may be useful alternatives to conventional ion-selective electrodes sensitive to F(-) ion. Furthermore, FcBA derivatives have been studied to construct lectin; steroids; nucleotides; salicylic acid; and bacteria sensors. One of the limitations of FcBA-based sensors comes from the fact that FcBA derivatives are added in sample solutions as reagents. FcBA derivatives should be immobilized on the surface of electrodes for developing reagentless sensors. PMID:25587421

  18. Combined anticalcification treatment of bovine pericardium with decellularization and hyaluronic acid derivative.

    PubMed

    Zhu, Deyi; Jin, Liqiang; Wang, Xuemei; Xu, Li; Liu, Tianqi

    2014-01-01

    The objective of this work was to evaluate the effect of decellularization and hyaluronic acid derivative on the improvement of anticalcification of glutaraldehyde fixed bovine pericardium (GFBP) using a rat subcutaneous implantation model A cell extraction process was employed to remove the cells and cellular components from bovine pericardium (BP), leaving a framework of largely insoluble collagen. Then acellular BP was cross-linked by glutaraldehyde solution and treated with hyaluronic acid derivative (HA-ADH) which was obtained by coupling adipic dihydrazide (ADH) on-COOH of hyaluronic acid (HA). The results of in vivo calcification tests showed that the calcium content was decreased dramatically by decellularization alone (from 28.07 ± 18.87 to 2.44 ± 0.55 μg Ca/mg dry tissue after 8 weeks' implantation), and even less concentration was shown by the combination of HA derivative treatment and decellularization (GFaBP-HA group) (0.25 ± 0.08 μg Ca/mg dry tissue after 8 weeks' implantation). In addition, GFaBP-HA group not only presented a lower degree of calcification, but also showed lower ratios of Ca/P molar, which corresponded to amorphous calcium phosphates. The obtained results indicated that GFaBP-HA was a potential candidate for the manufacture of anticalcification bioprostheses. PMID:24211959

  19. Effect of pH on fecal recovery of energy derived from volatile fatty acids.

    PubMed

    Kien, C L; Liechty, E A

    1987-01-01

    We assessed the effect of pH on volatilization of short-chain fatty acids during lyophilization. Acetic, propionic, valeric, and butyric acids were added to a fecal homogenate in amounts sufficient to raise the energy density by 18-27%. Fecal homogenate samples were either acidified (pH 2.8-3.2), alkalinized (pH 7.9-8.7), or left unchanged (4.0-4.8) prior to lyophilization and subsequent bomb calorimetry. Alkalinizing the fecal samples prevented the 20% loss of energy derived from each of these volatile fatty acids observed in samples either acidified or without pH adjustment. These data suggest that in energy balance studies involving subjects with active colonic fermentation, fecal samples should be alkalinized prior to lyophilization and bomb calorimetry. PMID:3681570

  20. Spectroscopic determination of acid dissociation constants of N-substituted-6-acylbenzothiazolone derivatives.

    PubMed

    Sıdır, Yadigar Gülseven; Sıdır, Isa; Berber, Halil

    2011-05-26

    The acid dissociation constants of twelve novel drug precursor N-substituted-6-acylbenzothiazolone derivatives were determined by using the UV-vis spectroscopic technique. The protonation and deprotonation behaviors of the investigated molecules were researched from the super basic to super acid regions (i.e., 8 mol·L(-1) KOH to 98% H(2)SO(4)) including the pH region. It is observed that all of the molecules are protonated in the super acidic region. The calculated relative stability values of possible tautomer structures indicate that the keto form of investigated molecules is favored over the enol form. It was predicted that protonation occurs at the amide (oxo) group found in the keto form.

  1. Synthesis and Cytotoxic Activity on Human Cancer Cells of Novel Isoquinolinequinone-Amino Acid Derivatives.

    PubMed

    Valderrama, Jaime A; Delgado, Virginia; Sepúlveda, Sandra; Benites, Julio; Theoduloz, Cristina; Buc Calderon, Pedro; Muccioli, Giulio G

    2016-09-08

    A variety of aminoisoquinoline-5,8-quinones bearing α-amino acids moieties were synthesized from 3-methyl-4-methoxycarbonylisoquinoline-5,8-quinone and diverse l- and d-α-amino acid methyl esters. The members of the series were evaluated for their cytotoxic activity against normal and cancer cell lines by using the (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) assay. From the current investigation, structure-activity relationships demonstrate that the location and structure of the amino acid fragment plays a significant role in the cytotoxic effects. Moderate to high cytotoxic activity was observed and four members, derived from l-alanine, l-leucine, l-phenylalanine, and d-phenylalanine, were selected as promising compounds by their IC50 ranging from 0.5 to 6.25 μM and also by their good selectivity indexes (≥2.24).

  2. Quantitative structure-activity relationships of antimicrobial fatty acids and derivatives against Staphylococcus aureus *

    PubMed Central

    Zhang, Hui; Zhang, Lu; Peng, Li-juan; Dong, Xiao-wu; Wu, Di; Wu, Vivian Chi-Hua; Feng, Feng-qin

    2012-01-01

    Fatty acids and derivatives (FADs) are resources for natural antimicrobials. In order to screen for additional potent antimicrobial agents, the antimicrobial activities of FADs against Staphylococcus aureus were examined using a microplate assay. Monoglycerides of fatty acids were the most potent class of fatty acids, among which monotridecanoin possessed the most potent antimicrobial activity. The conventional quantitative structure-activity relationship (QSAR) and comparative molecular field analysis (CoMFA) were performed to establish two statistically reliable models (conventional QSAR: R 2=0.942, Q 2 LOO=0.910; CoMFA: R 2=0.979, Q 2=0.588, respectively). Improved forecasting can be achieved by the combination of these two models that provide a good insight into the structure-activity relationships of the FADs and that may be useful to design new FADs as antimicrobial agents. PMID:22302421

  3. Hybrid Compounds Strategy in the Synthesis of Oleanolic Acid Skeleton-NSAID Derivatives.

    PubMed

    Pawełczyk, Anna; Olender, Dorota; Sowa-Kasprzak, Katarzyna; Zaprutko, Lucjusz

    2016-04-12

    The current study focuses on the synthesis of several hybrid individuals combining a natural oleanolic acid skeleton and synthetic nonsteroidal anti-inflammatory drug moieties (NSAIDs). It studied structural modifications of the oleanolic acid structure by use of the direct reactivity of hydroxyl or hydroxyimino groups at position C-3 of the triterpenoid skeleton with the carboxylic function of anti-inflammatory drugs leading to new perspective compounds with high potential pharmacological activities. Novel ester- and iminoester-type derivatives of oleanolic unit with the different NSAIDs, such as ibuprofen, aspirin, naproxen, and ketoprofen, were obtained and characterized. Moreover, preliminary research of compounds obtaining structure stability under acidic conditions was examined and the PASS method of prediction of activity spectra for substances was used to estimate the potential biological activity of these compounds.

  4. Novel quinolinonyl diketo acid derivatives as HIV-1 integrase inhibitors: design, synthesis, and biological activities.

    PubMed

    Di Santo, Roberto; Costi, Roberta; Roux, Alessandra; Miele, Gaetano; Crucitti, Giuliana Cuzzucoli; Iacovo, Alberto; Rosi, Federica; Lavecchia, Antonio; Marinelli, Luciana; Di Giovanni, Carmen; Novellino, Ettore; Palmisano, Lucia; Andreotti, Mauro; Amici, Roberta; Galluzzo, Clementina Maria; Nencioni, Lucia; Palamara, Anna Teresa; Pommier, Yves; Marchand, Christophe

    2008-08-14

    Novel quinolinonyl diketo acids were designed to obtain integrase (IN) inhibitors selectively active against the strand transfer (ST) step of the HIV integration process. Those new compounds are characterized by a single aryl diketo acid (DKA) chain in comparison to 4, a bifunctional diketo acid reported by our group as an anti-IN agent highly potent against both the 3'-processing and ST steps. Compound 6d was the most potent derivative in IN enzyme assays, while 6i showed the highest potency against HIV-1 in acutely infected cells. The selective inhibition of ST suggested the newly designed monofunctional DKAs bind the IN-DNA acceptor site without affecting the DNA donor site.

  5. Effect of pH on fecal recovery of energy derived from volatile fatty acids.

    PubMed

    Kien, C L; Liechty, E A

    1987-01-01

    We assessed the effect of pH on volatilization of short-chain fatty acids during lyophilization. Acetic, propionic, valeric, and butyric acids were added to a fecal homogenate in amounts sufficient to raise the energy density by 18-27%. Fecal homogenate samples were either acidified (pH 2.8-3.2), alkalinized (pH 7.9-8.7), or left unchanged (4.0-4.8) prior to lyophilization and subsequent bomb calorimetry. Alkalinizing the fecal samples prevented the 20% loss of energy derived from each of these volatile fatty acids observed in samples either acidified or without pH adjustment. These data suggest that in energy balance studies involving subjects with active colonic fermentation, fecal samples should be alkalinized prior to lyophilization and bomb calorimetry.

  6. Synthesis and Cytotoxic Activity on Human Cancer Cells of Novel Isoquinolinequinone-Amino Acid Derivatives.

    PubMed

    Valderrama, Jaime A; Delgado, Virginia; Sepúlveda, Sandra; Benites, Julio; Theoduloz, Cristina; Buc Calderon, Pedro; Muccioli, Giulio G

    2016-01-01

    A variety of aminoisoquinoline-5,8-quinones bearing α-amino acids moieties were synthesized from 3-methyl-4-methoxycarbonylisoquinoline-5,8-quinone and diverse l- and d-α-amino acid methyl esters. The members of the series were evaluated for their cytotoxic activity against normal and cancer cell lines by using the (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) assay. From the current investigation, structure-activity relationships demonstrate that the location and structure of the amino acid fragment plays a significant role in the cytotoxic effects. Moderate to high cytotoxic activity was observed and four members, derived from l-alanine, l-leucine, l-phenylalanine, and d-phenylalanine, were selected as promising compounds by their IC50 ranging from 0.5 to 6.25 μM and also by their good selectivity indexes (≥2.24). PMID:27617997

  7. E-cinnamic acid derivatives and phenolics from Chilean strawberry fruits, Fragaria chiloensis ssp. chiloensis.

    PubMed

    Cheel, José; Theoduloz, Cristina; Rodríguez, Jaime; Saud, Guillermo; Caligari, Peter D S; Schmeda-Hirschmann, Guillermo

    2005-11-01

    Three E-cinnamic acid glycosides, tryptophan, and cyanidin-3-O-beta-D-glucopyranoside were isolated from ripe fruits of the Chilean strawberry Fragaria chiloensis ssp. chiloensis. 1-O-E-Cinnamoyl-beta-D-xylopyranoside, 1-O-E-cinnamoyl-beta-D-rhamnopyranoside, and 1-O-E-cinnamoyl-alpha-xylofuranosyl-(1-->6)-beta-D-glucopyranose are reported for the first time. The cinnamic acid glycosides and aromatic compound patterns in F. chiloensis fruits were determined by high-performance liquid chromatography (HPLC). HPLC analyses of extracts showed that cyanidin-3-O-beta-D-glucopyranoside and free ellagic acid are present in achenes while the E-cinnamoyl derivatives and tryptophan were identified only in the thalamus. The free radical scavenging effect of the fruit extract can be associated with the anthocyanin content.

  8. Development of novel ferulic acid derivatives as potent histone deacetylase inhibitors.

    PubMed

    Wang, Fang; Lu, Wen; Zhang, Tao; Dong, Jinyun; Gao, Hongping; Li, Pengfei; Wang, Sicen; Zhang, Jie

    2013-11-15

    Histone deacetylase inhibitors (HDACIs) offer a promising strategy for cancer therapy. The discovery of potent ferulic acid-based HDACIs with hydroxamic acid or 2-aminobenzamide group as zinc binding group was reported. The halogeno-acetanilide was introduced as novel surface recognition moiety (SRM). The majority of title compounds displayed potent HDAC inhibitory activity. In particular, FA6 and FA16 exhibited significant enzymatic inhibitory activities, with IC50 values of 3.94 and 2.82 μM, respectively. Furthermore, these compounds showed moderate antiproliferative activity against a panel of human cancer cells. FA17 displayed promising profile as an antitumor candidate. The results indicated that these ferulic acid derivatives could serve as promising lead compounds for further optimization. PMID:24095016

  9. Phenalenone derivatives and the unusual tricyclic sesterterpene acid from the marine fungus Lophiostoma bipolare BCC25910.

    PubMed

    Intaraudom, Chakapong; Nitthithanasilp, Sutichai; Rachtawee, Pranee; Boonruangprapa, Tanapong; Prabpai, Samran; Kongsaeree, Palangpon; Pittayakhajonwut, Pattama

    2015-12-01

    Ten compounds including nine phenalenone derivatives (five bipolarides and four bipolarols) and a sesterterpene acid (bipolarenic acid), were isolated from a marine isolated of the fungus Lophiostoma bipolare (BCC25910), along with the known compounds, (-)-scleroderolide, (-)-sclerodin, and oxasetin. Chemical structures were elucidated based on NMR spectroscopic data and HRESIMS analysis. In addition, the absolute configurations of the phenalenones were resolved using specific rotations and chemical means, while the relative configuration of bipolarenic acid was confirmed by X-ray crystallographic analysis. The compounds were evaluated for biological activity against the Plasmodium falciparum K-1 strain, Candida albicans, and Bacillus cereus, and for cytotoxicity against both cancerous and non-cancerous cells. PMID:26582262

  10. E-cinnamic acid derivatives and phenolics from Chilean strawberry fruits, Fragaria chiloensis ssp. chiloensis.

    PubMed

    Cheel, José; Theoduloz, Cristina; Rodríguez, Jaime; Saud, Guillermo; Caligari, Peter D S; Schmeda-Hirschmann, Guillermo

    2005-11-01

    Three E-cinnamic acid glycosides, tryptophan, and cyanidin-3-O-beta-D-glucopyranoside were isolated from ripe fruits of the Chilean strawberry Fragaria chiloensis ssp. chiloensis. 1-O-E-Cinnamoyl-beta-D-xylopyranoside, 1-O-E-cinnamoyl-beta-D-rhamnopyranoside, and 1-O-E-cinnamoyl-alpha-xylofuranosyl-(1-->6)-beta-D-glucopyranose are reported for the first time. The cinnamic acid glycosides and aromatic compound patterns in F. chiloensis fruits were determined by high-performance liquid chromatography (HPLC). HPLC analyses of extracts showed that cyanidin-3-O-beta-D-glucopyranoside and free ellagic acid are present in achenes while the E-cinnamoyl derivatives and tryptophan were identified only in the thalamus. The free radical scavenging effect of the fruit extract can be associated with the anthocyanin content. PMID:16248546

  11. Novel cinnamic acid derivatives as antioxidant and anticancer agents: design, synthesis and modeling studies.

    PubMed

    Pontiki, Eleni; Hadjipavlou-Litina, Dimitra; Litinas, Konstantinos; Geromichalos, George

    2014-07-07

    Cinnamic acids have been identified as interesting compounds with antioxidant, anti-inflammatory and cytotoxic properties. In the present study, simple cinnamic acids were synthesized by Knoevenagel condensation reactions and evaluated for the above biological activities. Compound 4ii proved to be the most potent LOX inhibitor. Phenyl- substituted acids showed better inhibitory activity against soybean LOX, and it must be noted that compounds 4i and 3i with higher lipophilicity values resulted less active than compounds 2i and 1i. The compounds have shown very good activity in different antioxidant assays. The antitumor properties of these derivatives have been assessed by their 1/IC50 inhibitory values in the proliferation of HT-29, A-549, OAW-42, MDA-MB-231, HeLa and MRC-5 normal cell lines. The compounds presented low antitumor activity considering the IC50 values attained for the cell lines, with the exception of compound 4ii. Molecular docking studies were carried out on cinnamic acid derivative 4ii and were found to be in accordance with our experimental biological results.

  12. High-performance liquid chromatographic determination of linoleic acid peroxide-derived radicals using electrochemical detection.

    PubMed

    Iwahashi, H

    2000-12-29

    High-performance liquid chromatography-electrochemical detection (HPLC-ED) was applied to detect 13-hydroperoxide octadecadienoic acid (13-HPODE)-derived radicals such as the pentyl radical and octanoic acid radical. The 13-HPODE-derived radicals were successfully detected using HPLC-ED by the combined use of the spin-trapping technique with alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (4-POBN). The 4-POBN-pentyl radical adduct was detected at the retention time of 18.2 +/- 0.3 min on the elution profile of HPLC-ED with an ODS column (15 cm x 4.6 mm I.D.) using a flow-rate of 1.0 ml/min with 50 mM ammonium acetate in 29% (v/v) aqueous acetonitrile. The 4-POBN-octanoic acid radical adduct was also detected at the retention time of 13.7 +/- 0.7 min using a flow-rate of 1.0 ml/min with 50 mM ammonium acetate in 14% (v/v) aqueous acetonitrile. The concentrations of the 4-POBN radical adducts were determined using HPLC-ED without an internal standard. HPLC-ED is 100 times as sensitive as HPLC-electron spin resonance (ESR) under the ESR and ED conditions employed here. Even 1.8 pmol of the 4-POBN-pentyl (or octanoic acid) radical adduct was detectable using PMID:11204234

  13. Optical and thermal properties of azo derivatives of salicylic acid thin films

    NASA Astrophysics Data System (ADS)

    Ghoneim, M. M.; El-Ghamaz, N. A.; El-Sonbati, A. Z.; Diab, M. A.; El-Bindary, A. A.; Serag, L. S.

    2015-02-01

    N-acryloyl-4-aminosalicylic acid (4-AMSA), monomer (HL) and 5-(4‧-alkyl phenylazo)-N-acryloyl-4-aminosalicylic acid (HLn) are synthesized and characterized with various physico-chemical techniques. Thin films of 5-(4‧-alkyl phenylazo)-N-acryloyl-4-aminosalicylic acid (HLn) are prepared by spin coating technique. The X-ray diffraction (XRD) patterns of 4-aminosalicylic acid (4-ASA) and its derivatives are investigated in powder and thin film forms. Thermal properties of the compounds are investigated by thermogravemetric analysis (TGA). The optical energy gap and the type of optical transition are investigated in the wavelength range (200-2500 nm) for 4-ASA, HL and HLn. The values of fundamental energy gap (Eg) are in the range 3.60-3.69 eV for all compounds and the type of optical transition is found to be indirect allowed. The onset energy gap Eg∗ appeared only for azodye compounds is found to be in the range 0.95-1.55 eV depending on the substituent function groups. The refractive index, n, shows a normal dispersion in the wavelength range 650-2500 nm, while shows anomalous dispersion in the wavelength rang 200-650 nm. The dispersion parameters ε∞, εL, Ed, Eo and N /m∗ are calculated. The photoluminescence phenomena (PL) appear for thin films of 4-ASA and its derivatives show three main emission transitions.

  14. Synthesis and biological evaluation of quinic acid derivatives as anti-inflammatory agents.

    PubMed

    Zeng, Kui; Thompson, Karin Emmons; Yates, Charles R; Miller, Duane D

    2009-09-15

    Quinic acid (QA) esters found in hot water extracts of Uncaria tomentosa (a.k.a. cat's claw) exert anti-inflammatory activity through mechanisms involving inhibition of the pro-inflammatory transcription factor nuclear factor kappa B (NF-kappaB). Herein, we describe the synthesis and biological testing of novel QA derivatives. Inhibition of NF-kappaB was assessed using A549 (Type II alveolar epithelial-like) cells that stably express a secreted alkaline phosphatase (SEAP) reporter driven by an NF-kappaB response element. A549-NF-kappaB cells were stimulated with TNF-alpha (10 ng/mL) in the presence or absence of QA derivative for 18 hours followed by measurement of SEAP activity. Amide substitution at the carboxylic acid position yielded potent inhibitors of NF-kappaB. A variety of modifications to the amide substitution were tolerated with the N-propyl amide derivative being the most potent. Further examination of the SAR demonstrated that acetylation of the hydroxyl groups reduced NF-kappaB inhibitory activity. QA amide derivatives lacked anti-oxidant activity and were found to be neither anti-proliferative nor cytotoxic at concentrations up to 100 microM. In conclusion, we have discovered a novel series of non-toxic QA amides that potently inhibit NF-kappaB, despite their lack of anti-oxidant activity. Mechanistic studies and pre-clinical efficacy studies in various inflammatory animal models are on-going.

  15. Synthesis, evaluation and molecular docking studies of amino acid derived N-glycoconjugates as antibacterial agents.

    PubMed

    Baig, Noorullah; Singh, Rajnish Prakash; Chander, Subhash; Jha, Prabhat Nath; Murugesan, Sankaranarayanan; Sah, Ajay K

    2015-12-01

    Six amino acid derived N-glycoconjugates of d-glucose were synthesized, characterized and tested for antibacterial activity against G(+)ve (Bacillus cereus) as well as G(-)ve (Escherichia coli and Klebsiella pneumoniae) bacterial strains. All the tested compounds exhibited moderate to good antibacterial activity against these bacterial strains. The results were compared with the antibacterial activity of standard drug Chloramphenicol, where results of A5 (Tryptophan derived glycoconjugates) against E. coli and A4 (Isoleucine derived glycoconjugates) against K. pneumoniae bacterial strains are comparable with the standard drug molecule. In silico docking studies were also performed in order to understand the mode of action and binding interactions of these molecules. The docking studies revealed that, occupation of compound A5 at the ATP binding site of subunit GyrB (DNA gyrase, PDB ID: 3TTZ) via hydrophobic and hydrogen bonding interactions may be the reason for its significant in vitro antibacterial activity.

  16. Quantitative structure activity relationships of some pyridine derivatives as corrosion inhibitors of steel in acidic medium.

    PubMed

    El Ashry, El Sayed H; El Nemr, Ahmed; Ragab, Safaa

    2012-03-01

    Quantum chemical calculations using the density functional theory (B3LYP/6-31G DFT) and semi-empirical AM1 methods were performed on ten pyridine derivatives used as corrosion inhibitors for mild steel in acidic medium to determine the relationship between molecular structure and their inhibition efficiencies. Quantum chemical parameters such as total negative charge (TNC) on the molecule, energy of highest occupied molecular orbital (E (HOMO)), energy of lowest unoccupied molecular orbital (E (LUMO)) and dipole moment (μ) as well as linear solvation energy terms, molecular volume (Vi) and dipolar-polarization (π) were correlated to corrosion inhibition efficiency of ten pyridine derivatives. A possible correlation between corrosion inhibition efficiencies and structural properties was searched to reduce the number of compounds to be selected for testing from a library of compounds. It was found that theoretical data support the experimental results. The results were used to predict the corrosion inhibition of 24 related pyridine derivatives.

  17. Protective effect of bile acid derivatives in phalloidin-induced rat liver toxicity

    SciTech Connect

    Herraez, Elisa; Macias, Rocio I.R.; Vazquez-Tato, Jose; Hierro, Carlos; Monte, Maria J.; Marin, Jose J.G.

    2009-08-15

    Phalloidin causes severe liver damage characterized by marked cholestasis, which is due in part to irreversible polymerization of actin filaments. Liver uptake of this toxin through the transporter OATP1B1 is inhibited by the bile acid derivative BALU-1, which does not inhibit the sodium-dependent bile acid transporter NTCP. The aim of the present study was to investigate whether BALU-1 prevents liver uptake of phalloidin without impairing endogenous bile acid handling and hence may have protective effects against the hepatotoxicity induced by this toxin. In anaesthetized rats, i.v. administration of BALU-1 increased bile flow more than taurocholic acid (TCA). Phalloidin administration decreased basal (- 60%) and TCA-stimulated bile flow (- 55%) without impairing bile acid output. Phalloidin-induced cholestasis was accompanied by liver necrosis, nephrotoxicity and haematuria. In BALU-1-treated animals, phalloidin-induced cholestasis was partially prevented. Moreover haematuria was not observed, which was consistent with histological evidences of BALU-1-prevented injury of liver and kidney tissue. HPLC-MS/MS analysis revealed that BALU-1 was secreted in bile mainly in non-conjugated form, although a small proportion (< 5%) of tauro-BALU-1 was detected. BALU-1 did not inhibit the biliary secretion of endogenous bile acids. When highly choleretic bile acids, - ursodeoxycholic (UDCA) and dehydrocholic acid (DHCA) - were administered, they were found less efficient than BALU-1 in preventing phalloidin-induced cholestasis. Biliary phalloidin elimination was low but it was increased by BALU-1 > TCA > DHCA > UDCA. In conclusion, BALU-1 is able to protect against phalloidin-induced hepatotoxicity, probably due to an inhibition of the liver uptake and an enhanced biliary secretion of this toxin.

  18. Metal cation dependence of interactions with amino acids: bond dissociation energies of Rb(+) and Cs(+) to the acidic amino acids and their amide derivatives.

    PubMed

    Armentrout, P B; Yang, Bo; Rodgers, M T

    2014-04-24

    Metal cation-amino acid interactions are key components controlling the secondary structure and biological function of proteins, enzymes, and macromolecular complexes comprising these species. Determination of pairwise interactions of alkali metal cations with amino acids provides a thermodynamic vocabulary that begins to quantify these fundamental processes. In the present work, we expand a systematic study of such interactions by examining rubidium and cesium cations binding with the acidic amino acids (AA), aspartic acid (Asp) and glutamic acid (Glu), and their amide derivatives, asparagine (Asn) and glutamine (Gln). These eight complexes are formed using electrospray ionization and their bond dissociation energies (BDEs) are determined experimentally using threshold collision-induced dissociation with xenon in a guided ion beam tandem mass spectrometer. Analyses of the energy-dependent cross sections include consideration of unimolecular decay rates, internal energy of the reactant ions, and multiple ion-neutral collisions. Quantum chemical calculations are conducted at the B3LYP, MP2(full), and M06 levels of theory using def2-TZVPPD basis sets, with results showing reasonable agreement with experiment. At 0 and 298 K, most levels of theory predict that the ground-state conformers for M(+)(Asp) and M(+)(Asn) involve tridentate binding of the metal cation to the backbone carbonyl, amino, and side-chain carbonyl groups, although tridentate binding to the carboxylic acid group and side-chain carbonyl is competitive for M(+)(Asn). For the two longer side-chain amino acids, Glu and Gln, multiple structures are competitive. A comparison of these results to those for the smaller alkali cations, Na(+) and K(+), provides insight into the trends in binding energies associated with the molecular polarizability and dipole moment of the side chain. For all four metal cations, the BDEs are inversely correlated with the size of the metal cation and follow the order Asp < Glu

  19. Urolithins, ellagic acid-derived metabolites produced by human colonic microflora, exhibit estrogenic and antiestrogenic activities.

    PubMed

    Larrosa, Mar; González-Sarrías, Antonio; García-Conesa, María Teresa; Tomás-Barberán, Francisco A; Espín, Juan Carlos

    2006-03-01

    Urolithins A and B (hydroxy-6H-dibenzo[b,d]pyran-6-one derivatives) are colonic microflora metabolites recently proposed as biomarkers of human exposure to dietary ellagic acid derivatives. Molecular models suggest that urolithins could display estrogenic and/or antiestrogenic activity. To this purpose, both urolithins and other known phytoestrogens (genistein, daidzein, resveratrol, and enterolactone) were assayed to evaluate the capacity to induce cell proliferation on the estrogen-sensitive human breast cancer MCF-7 cells as well as the ability to bind to alpha- and beta-estrogen receptors. Both urolithins A and B showed estrogenic activity in a dose-dependent manner even at high concentrations (40 microM), without antiproliferative or toxic effects, whereas the other phytoestrogens inhibited cell proliferation at high concentrations. Overall, urolithins showed weaker estrogenic activity than the other phytoestrogens. However, both urolithins displayed slightly higher antiestrogenic activity (antagonized the growth promotion effect of 17-beta-estradiol in a dose-dependent manner) than the other phytoestrogens. The IC(50) values for the ERalpha and ERbeta binding assays were 0.4 and 0.75 microM for urolithin A; 20 and 11 microM for urolithin B; 3 and 0.02 for genistein; and 2.3 and 1 for daidzein, respectively; no binding was detected for resveratrol and enterolactone. Urolithins A and B entered into MCF-7 cells and were metabolized to yield mainly urolithin-sulfate derivatives. These results, together with previous studies regarding absorption and metabolism of dietary ellagitannins and ellagic acid in humans, suggest that the gut microflora metabolites urolithins are potential endocrine-disrupting molecules, which could resemble other described "enterophytoestrogens" (microflora-derived metabolites with estrogenic/antiestrogenic activity). Further research is warranted to evaluate the possible role of ellagitannins and ellagic acid as dietary "pro-phytoestrogens".

  20. Use of humic acids derived from peat and lignite as phenanthrene sorbents

    NASA Astrophysics Data System (ADS)

    Sofikitis, Elias; Giannouli, Andriana; Kalaitzidis, Stavros; Christanis, Kimon; Karapanagioti, Hrissi K.; Papanicolaou, Cassiani

    2015-04-01

    A broad range of materials is being applied for environmental remediation of water, among them sorbents such as humic acids. Being natural substances, the extraction and purification of humic acids might be cheaper than the production of synthetic sorbents. Having higher absorbing capacity than most of the sorbents used to date, humic acids have a competitive advantage against commonly used sorbents such as active charcoals and biochar. Humic acids are "complex colloidal super-mixtures" that are characterized by their functional groups. Therefore, composition and molecular formula can vary depending on the properties of the parent material. The aim of this project was (a) to study the sorption capacity of humic acids derived from peat and lignite samples picked up from deposits spread throughout Greece and (b) to compare the results with these of the parent materials. This comparison provides an insight to which matrix samples are suitable for further chemical treatment for the isolation of humic acids to be used as sorbents. The selected model pollutant was phenanthrene, which is a PAH that consists of three fused benzene rings. Humic acids were extracted according to the methodology proposed by the IHSS, slightly modified, in order to fit better to the properties of organic sediments. Sorption experiments were conducted by mixing 0.004 g of the sorbent (peat or lignite or humic acid) with aqueous solutions of phenanthrene at different concentrations of 30, 50, 100, 300, and 500 μg/L. The results show that phenanthrene sorption is higher for the humic acid than for the original lignite and peat samples. The original samples display higher sorption at the lower phenanthere solutions (30 μg/L; Kd ranges from 15,000 to 47,000 L/kg) than at the higher one (500 μg/L; Kd ranges from 4,100 to 13,000 L/Kg) suggesting non-linear sorption. The humic acids display mainly linear isotherms with Kd ranges from 6,600 to 120,000 L/kg. Concerning the suitability of the studied

  1. Hyperthermic effects of D-lysergic acid diethylamide (LSD) and its derivatives in rabbits and rats.

    PubMed

    Hashimoto, H; Hayashi, M; Nakahara, Y; Niwaguchi, T; Ishii, H

    1977-08-01

    Several D-lysergic acid diethylamide (LSD) derivatives including metabolites of LSD in animals liver and Streptomyces such as D-lysergic acid ethyl, 2-hydroxyethylamide (LEO), D-lysergic acid ethylamide (LAE), D-norlysergic acid diethylamide (norLSD) and synthetic N6-allyl-D-norlysergic acid diethylamide (allyl-nor LSD) were studied with rabbits and rats. In rabbits, the order of the hyperthermic activities was allyl-norLSD greater than LSD greater than LEO, LAE, nor-LSD, and this order was parallel to that of 5-hydroxytryptamine-like activities of these compounds which was previously studied. However, the order was LAE greater than LSD greater than norLSD IN RATS. The hyperthermic effect of LSD in rabbits was attenuated by methysergide, but not by atropine when these drugs were intraventricularly administered. These results suggest the possibility that the metabolites of LSD contribute to the hyperthermic effect of LSD in rats but not in rabbits, and support the idea that 5-HT receptors are involved in the hyperthermia induced by LSD in rabbits.

  2. Production of chlorogenic acid and its derivatives in hairy root cultures of Stevia rebaudiana.

    PubMed

    Fu, Xiao; Yin, Zhong-Ping; Chen, Ji-Guang; Shangguan, Xin-Chen; Wang, Xiaoqiang; Zhang, Qing-Feng; Peng, Da-Yong

    2015-01-14

    Chlorogenic acid and its derivatives (CADs) are valuable bioactive plant secondary metabolites with many health benefits. In the present study, Stevia rebaudiana hairy root cultures were established, and the culture conditions for the production of CADs were optimized. The hairy roots were induced by coculture of S. rebaudiana leaves and Agrobacterium rhizogenes (C58C1) after infection, which were further verified by PCR detection of rolB and rolC genes. HPLC-MS and HPLC analysis showed that chlorogenic acid (3-caffeoylquinic acid, 3-CQA), 3,5-dicaffeoylquinic acid (3,5-CQA), and 4,5-dicaffeoylquinic acid (4,5-CQA) were the major CADs in the hairy roots. Eight single roots with rapid growth rate were selected. Among them, T3 had the highest yield of CADs. B5 medium supplemented with 40 g/L sucrose was more suitable for the production of CADs than others. Under optimal culture conditions, the total content of these three compounds reached 105.58 mg/g and total yield was 234.40 mg/100 mL.

  3. Changes in caffeic acid derivatives in sweet potato (Ipomoea batatas L.) during cooking and processing.

    PubMed

    Takenaka, Makiko; Nanayama, Kazuko; Isobe, Seiichiro; Murata, Masatsune

    2006-01-01

    There was an obvious decrease in caffeic acid derivatives during the boiling of cube-shaped blocks of sweet potatoes. They also decreased in a mixture of freeze-dried sweet-potato powder and water maintained at room temperature. Ascorbic acid prevented the decrease, supporting the occurrence of an enzyme reaction with polyphenol oxidase (PPO). 5-O-Caffeoylquinic acid (5-CQA, "3-O-caffeoylquinic acid" as a trivial name) and 3,5-di-O-caffeoylquinic acid (3,5-CQA), major phenolic compounds of sweet potato, did not change when they were separately heated in boiling water. When the mixture of powdered sweet potato and water was heated at 100 degrees C, there was only a negligible decrease in the total amount of phenolic compounds, and portions of 5-CQA and 3,5-CQA were found to be isomerized to 3-CQA, 4-CQA, 3,4-CQA, and 4,5-CQA. The content and composition of the phenolic compounds in sweet potatoes differed between fresh and long-stored ones, as did their response to heating.

  4. Chirality of meteoritic free and IOM-derived monocarboxylic acids and implications for prebiotic organic synthesis

    NASA Astrophysics Data System (ADS)

    Aponte, José C.; Tarozo, Rafael; Alexandre, Marcelo R.; Alexander, Conel M. O.'D.; Charnley, Steven B.; Hallmann, Christian; Summons, Roger E.; Huang, Yongsong

    2014-04-01

    The origin of homochirality and its role in the development of life on Earth are among the most intriguing questions in science. It has been suggested that carbonaceous chondrites seeded primitive Earth with the initial organic compounds necessary for the origin of life. One of the strongest pieces of evidence supporting this theory is that certain amino acids in carbonaceous chondrites display a significant L-enantiomeric excess (ee), similar to those use by terrestrial life. Analyses of ee in meteoritic molecules other than amino acids would shed more light on the origins of homochirality. In this study we investigated the stereochemistry of two groups of compounds: (1) free monocarboxylic acids (MCAs) from CM2 meteorites LON 94101 and Murchison; and (2) the aliphatic side chains present in the insoluble organic matter (IOM) and extracted in the form of monocarboxylic acids (MCAs) from EET 87770 (CR2) and Orgueil (CI1). Contrary to the well-known ee observed for amino acids in meteorites, we found that meteoritic branched free and IOM-derived MCAs with 5-8 carbon atoms are essentially racemic. The racemic nature of these compounds is used to discuss the possible influence of ultraviolet circularly polarized light (UVCPL) and aqueous alterations on the parent body on chirality observed in in carbonaceous chondrites.

  5. Natural derivatives of diphenolic acid as substitutes for bisphenol-A

    NASA Astrophysics Data System (ADS)

    Ertl, Johanna; Cerri, Elisa; Rizzuto, Matteo; Caretti, Daniele

    2014-05-01

    Diphenolic acid had been originally used in the first epoxy resins and was later on forgotten as it was substituted by the cheaper bisphenol A. But in the recent years major health concerns have been raised as bisphenol A has a pseudo-hormonal effect on the body, playing the role of estrogen it can cause a severe impact on the organism, especially in males. Moreover it is produced from acetone and phenol, both from fossil, and thus limited resources. On the contrary, diphenolic acid is synthesized from levulinic acid and phenol. Levulinic acid being directly produced by hydrolysis of biomass. By substituting the fossil phenol with natural phenols from lignin or plant extraction we are able to synthesize a fully renewable substitute for bisphenol A. The reactions to yield an epoxy resin have been examined and the reactivity with epichlorohydrin is satisfying. Moreover, some of the derivatives of diphenolic acid have interesting curing properties and preliminary results show excellent properties of the cured resin, including thermal stability and pencil hardness.

  6. Acute larvicidal activity against mosquitoes and oxygen consumption inhibitory activity of dihydroguaiaretic acid derivatives.

    PubMed

    Nishiwaki, Hisashi; Tabara, Yoshimi; Kishida, Taro; Nishi, Kosuke; Shuto, Yoshihiro; Sugahara, Takuya; Yamauchi, Satoshi

    2015-03-11

    (-)-Dihydroguaiaretic acid (DGA) and its derivatives having 3-hydroxyphenyl (3-OH-DGA) and variously substituted phenyl groups instead of 3-hydroxy-4-methoxyphenyl groups were synthesized to measure their larvicidal activity against the mosquito Culex pipiens Linnaeus, 1758 (Diptera: Culicidae). Compared with DGA and 3-OH-DGA (LC50 (M), 3.52 × 10(-5) and 4.57 × 10(-5), respectively), (8R,8'R)-lignan-3-ol (3) and its 3-Me (10), 2-OH (12), 3-OH (13), and 2-OMe (15) derivatives showed low potency (ca. 6-8 × 10(-5) M). The 4-Me derivative (11) showed the lowest potency (12.1 × 10(-5) M), and the 2-F derivative (4) showed the highest (2.01 × 10(-5) M). All of the synthesized compounds induced an acute toxic symptom against mosquito larvae, with potency varying with the type and position of the substituents. The 4-F derivative (6), which killed larvae almost completely within 45 min, suppressed the O2 consumption of the mitochondrial fraction, demonstrating that this compound inhibited mitochondrial O2 consumption contributing to a respiratory inhibitory activity.

  7. Membrane protein complexes catalyze both 4- and 3-hydroxylation of cinnamic acid derivatives in monolignol biosynthesis.

    PubMed

    Chen, Hsi-Chuan; Li, Quanzi; Shuford, Christopher M; Liu, Jie; Muddiman, David C; Sederoff, Ronald R; Chiang, Vincent L

    2011-12-27

    The hydroxylation of 4- and 3-ring carbons of cinnamic acid derivatives during monolignol biosynthesis are key steps that determine the structure and properties of lignin. Individual enzymes have been thought to catalyze these reactions. In stem differentiating xylem (SDX) of Populus trichocarpa, two cinnamic acid 4-hydroxylases (PtrC4H1 and PtrC4H2) and a p-coumaroyl ester 3-hydroxylase (PtrC3H3) are the enzymes involved in these reactions. Here we present evidence that these hydroxylases interact, forming heterodimeric (PtrC4H1/C4H2, PtrC4H1/C3H3, and PtrC4H2/C3H3) and heterotrimeric (PtrC4H1/C4H2/C3H3) membrane protein complexes. Enzyme kinetics using yeast recombinant proteins demonstrated that the enzymatic efficiency (V(max)/k(m)) for any of the complexes is 70-6,500 times greater than that of the individual proteins. The highest increase in efficiency was found for the PtrC4H1/C4H2/C3H3-mediated p-coumaroyl ester 3-hydroxylation. Affinity purification-quantitative mass spectrometry, bimolecular fluorescence complementation, chemical cross-linking, and reciprocal coimmunoprecipitation provide further evidence for these multiprotein complexes. The activities of the recombinant and SDX plant proteins demonstrate two protein-complex-mediated 3-hydroxylation paths in monolignol biosynthesis in P. trichocarpa SDX; one converts p-coumaric acid to caffeic acid and the other converts p-coumaroyl shikimic acid to caffeoyl shikimic acid. Cinnamic acid 4-hydroxylation is also mediated by the same protein complexes. These results provide direct evidence for functional involvement of membrane protein complexes in monolignol biosynthesis.

  8. Fatty Acid Profile and Unigene-Derived Simple Sequence Repeat Markers in Tung Tree (Vernicia fordii)

    PubMed Central

    Zhang, Lin; Jia, Baoguang; Tan, Xiaofeng; Thammina, Chandra S.; Long, Hongxu; Liu, Min; Wen, Shanna; Song, Xianliang; Cao, Heping

    2014-01-01

    Tung tree (Vernicia fordii) provides the sole source of tung oil widely used in industry. Lack of fatty acid composition and molecular markers hinders biochemical, genetic and breeding research. The objectives of this study were to determine fatty acid profiles and develop unigene-derived simple sequence repeat (SSR) markers in tung tree. Fatty acid profiles of 41 accessions showed that the ratio of α-eleostearic acid was increasing continuously with a parallel trend to the amount of tung oil accumulation while the ratios of other fatty acids were decreasing in different stages of the seeds and that α-eleostearic acid (18∶3) consisted of 77% of the total fatty acids in tung oil. Transcriptome sequencing identified 81,805 unigenes from tung cDNA library constructed using seed mRNA and discovered 6,366 SSRs in 5,404 unigenes. The di- and tri-nucleotide microsatellites accounted for 92% of the SSRs with AG/CT and AAG/CTT being the most abundant SSR motifs. Fifteen polymorphic genic-SSR markers were developed from 98 unigene loci tested in 41 cultivated tung accessions by agarose gel and capillary electrophoresis. Genbank database search identified 10 of them putatively coding for functional proteins. Quantitative PCR demonstrated that all 15 polymorphic SSR-associated unigenes were expressed in tung seeds and some of them were highly correlated with oil composition in the seeds. Dendrogram revealed that most of the 41 accessions were clustered according to the geographic region. These new polymorphic genic-SSR markers will facilitate future studies on genetic diversity, molecular fingerprinting, comparative genomics and genetic mapping in tung tree. The lipid profiles in the seeds of 41 tung accessions will be valuable for biochemical and breeding studies. PMID:25167054

  9. A crystallographic fragment screen identifies cinnamic acid derivatives as starting points for potent Pim-1 inhibitors.

    PubMed

    Schulz, Michèle N; Fanghänel, Jörg; Schäfer, Martina; Badock, Volker; Briem, Hans; Boemer, Ulf; Nguyen, Duy; Husemann, Manfred; Hillig, Roman C

    2011-03-01

    A crystallographic fragment screen was carried out to identify starting points for the development of inhibitors of protein kinase Pim-1, a potential target for tumour therapy. All fragment hits identified via soaking in this study turned out to bind to the unusually hydrophobic pocket at the hinge region. The most potent fragments, two cinnamic acid derivatives (with a best IC(50) of 130 µM), additionally form a well defined hydrogen bond. The balance between hydrophobic and polar interactions makes these molecules good starting points for further optimization. Pim-2 inhibitors from a recently reported high-throughput screening campaign also feature a cinnamic acid moiety. Two of these Pim-2 inhibitors were synthesized, their potencies against Pim-1 were determined and their cocrystal structures were elucidated in order to determine to what degree the binding modes identified by fragment screening are conserved in optimized inhibitors. The structures show that the cinnamic acid moieties indeed adopt the same binding mode. Fragment screening thus correctly identified binding modes which are maintained when fragments are grown into larger and higher affinity inhibitors. The high-throughput screening-derived compound (E)-3-{3-[6-(4-aminocyclohexylamino)-pyrazin-2-yl]phenyl}acrylic acid (compound 1) is the most potent inhibitor of the cinnamic acid series for which the three-dimensional binding mode is known (IC(50) = 17 nM, K(d) = 28 nM). The structure reveals the molecular basis for the large gain in potency between the initial fragment hit and this optimized inhibitor.

  10. Generation and Dietary Modulation of Anti-Inflammatory Electrophilic Omega-3 Fatty Acid Derivatives

    PubMed Central

    Cipollina, Chiara; Salvatore, Sonia R.; Muldoon, Matthew F.; Freeman, Bruce A.; Schopfer, Francisco J.

    2014-01-01

    Dietary ω-3 polyunsaturated fatty acids (PUFAs) decrease cardiovascular risk via suppression of inflammation. The generation of electrophilic α,β-unsaturated ketone derivatives of the ω-3 PUFAs docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA) in activated human macrophages is catalyzed by cyclooxygenase-2 (Cox-2). These derivatives are potent pleiotropic anti-inflammatory signaling mediators that act via mechanisms including the activation of Nrf2-dependent phase 2 gene expression and suppression of pro-inflammatory NF-κB-driven gene expression. Herein, the endogenous generation of ω-3 PUFAs electrophilic ketone derivatives and their hydroxy precursors was evaluated in human neutrophils. In addition, their dietary modulation was assessed through a randomized clinical trial. Methods Endogenous generation of electrophilic omega-3 PUFAs and their hydroxy precursors was evaluated by mass spectrometry in neutrophils isolated from healthy subjects, both at baseline and upon stimulation with calcium ionophore. For the clinical trial, participants were healthy adults 30–55 years of age with a reported EPA+DHA consumption of ≤300 mg/day randomly assigned to parallel groups receiving daily oil capsule supplements for a period of 4 months containing either 1.4 g of EPA+DHA (active condition, n = 24) or identical appearing soybean oil (control condition, n = 21). Participants and laboratory technicians remained blinded to treatment assignments. Results 5-lypoxygenase-dependent endogenous generation of 7-oxo-DHA, 7-oxo-DPA and 5-oxo-EPA and their hydroxy precursors is reported in human neutrophils stimulated with calcium ionophore and phorbol 12-myristate 13-acetate (PMA). Dietary EPA+DHA supplementation significantly increased the formation of 7-oxo-DHA and 5-oxo-EPA, with no significant modulation of arachidonic acid (AA) metabolite levels. Conclusions The endogenous detection of these electrophilic ω-3 fatty acid ketone derivatives supports the

  11. Amino acid composition, including key derivatives of eccrine sweat: potential biomarkers of certain atopic skin conditions.

    PubMed

    Mark, Harker; Harding, Clive R

    2013-04-01

    The free amino acid (AA) composition of eccrine sweat is different from other biological fluids, for reasons which are not properly understood. We undertook the detailed analysis of the AA composition of freshly isolated pure human eccrine sweat, including some of the key derivatives of AA metabolism, to better understand the key biological mechanisms governing its composition. Eccrine sweat was collected from the axillae of 12 healthy subjects immediately upon formation. Free AA analysis was performed using an automatic AA analyser after ninhydrin derivatization. Pyrrolidine-5-carboxylic acid (PCA) and urocanic acid (UCA) levels were determined using GC/MS. The free AA composition of sweat was dominated by the presence of serine accounting for just over one-fifth of the total free AA composition. Glycine was the next most abundant followed by PCA, alanine, citrulline and threonine, respectively. The data obtained indicate that the AA content of sweat bears a remarkable similarity to the AA composition of the epidermal protein profilaggrin. This protein is the key source of free AAs and their derivatives that form a major part of the natural moisturizing factor (NMF) within the stratum corneum (SC) and plays a major role in maintaining the barrier integrity of human skin. As perturbations in the production of NMF can lead to abnormal barrier function and can arise as a consequence of filaggrin genotype, we propose the quantification of AAs in sweat may serve as a non-invasive diagnostic biomarker for certain atopic skin conditions, that is, atopic dermatitis (AD).

  12. Hydrothermal preparation and characterization of novel corncob-derived solid acid catalysts.

    PubMed

    Ma, Huan; Li, Jiabao; Liu, Weiwei; Cheng, Beijiu; Cao, Xiaoyan; Mao, Jingdong; Zhu, Suwen

    2014-06-11

    Novel corncob-derived solid acid catalysts were successfully synthesized for the first time by the hydrothermal method. The influences of different preparation conditions were investigated, and the structure-function relationships of the resulting catalysts were also discussed on the basis of the analysis of structure and composition. In comparison to conventional solid acid catalysts, the corncob-derived catalyst synthesized under optimized conditions exhibited higher catalytic activity in esterification reactions, yielding nearly 90% methyl oleate in only 2 h. The catalyst retained satisfactory catalytic activity for esterification, even after 8 reaction cycles. Solid-state magic angle spinning (MAS) (13)C nuclear magnetic resonance (NMR) investigations further indicated that the catalyst was composed of polycyclic aromatic carbon sheets bearing -SO3H, -COOH, and -OH groups in adequate amounts and with proper proportions, contributing to its excellent catalytic activity. This work provides a green method to synthesize solid acid catalysts from biomass wastes and may contribute to a holistic approach for biomass conversion. PMID:24820344

  13. Production of fatty acid-derived oleochemicals and biofuels by synthetic yeast cell factories.

    PubMed

    Zhou, Yongjin J; Buijs, Nicolaas A; Zhu, Zhiwei; Qin, Jiufu; Siewers, Verena; Nielsen, Jens

    2016-01-01

    Sustainable production of oleochemicals requires establishment of cell factory platform strains. The yeast Saccharomyces cerevisiae is an attractive cell factory as new strains can be rapidly implemented into existing infrastructures such as bioethanol production plants. Here we show high-level production of free fatty acids (FFAs) in a yeast cell factory, and the production of alkanes and fatty alcohols from its descendants. The engineered strain produces up to 10.4 g l(-1) of FFAs, which is the highest reported titre to date. Furthermore, through screening of specific pathway enzymes, endogenous alcohol dehydrogenases and aldehyde reductases, we reconstruct efficient pathways for conversion of fatty acids to alkanes (0.8 mg l(-1)) and fatty alcohols (1.5 g l(-1)), to our knowledge the highest titres reported in S. cerevisiae. This should facilitate the construction of yeast cell factories for production of fatty acids derived products and even aldehyde-derived chemicals of high value.

  14. Production of fatty acid-derived oleochemicals and biofuels by synthetic yeast cell factories.

    PubMed

    Zhou, Yongjin J; Buijs, Nicolaas A; Zhu, Zhiwei; Qin, Jiufu; Siewers, Verena; Nielsen, Jens

    2016-01-01

    Sustainable production of oleochemicals requires establishment of cell factory platform strains. The yeast Saccharomyces cerevisiae is an attractive cell factory as new strains can be rapidly implemented into existing infrastructures such as bioethanol production plants. Here we show high-level production of free fatty acids (FFAs) in a yeast cell factory, and the production of alkanes and fatty alcohols from its descendants. The engineered strain produces up to 10.4 g l(-1) of FFAs, which is the highest reported titre to date. Furthermore, through screening of specific pathway enzymes, endogenous alcohol dehydrogenases and aldehyde reductases, we reconstruct efficient pathways for conversion of fatty acids to alkanes (0.8 mg l(-1)) and fatty alcohols (1.5 g l(-1)), to our knowledge the highest titres reported in S. cerevisiae. This should facilitate the construction of yeast cell factories for production of fatty acids derived products and even aldehyde-derived chemicals of high value. PMID:27222209

  15. Production of fatty acid-derived oleochemicals and biofuels by synthetic yeast cell factories

    PubMed Central

    Zhou, Yongjin J.; Buijs, Nicolaas A.; Zhu, Zhiwei; Qin, Jiufu; Siewers, Verena; Nielsen, Jens

    2016-01-01

    Sustainable production of oleochemicals requires establishment of cell factory platform strains. The yeast Saccharomyces cerevisiae is an attractive cell factory as new strains can be rapidly implemented into existing infrastructures such as bioethanol production plants. Here we show high-level production of free fatty acids (FFAs) in a yeast cell factory, and the production of alkanes and fatty alcohols from its descendants. The engineered strain produces up to 10.4 g l−1 of FFAs, which is the highest reported titre to date. Furthermore, through screening of specific pathway enzymes, endogenous alcohol dehydrogenases and aldehyde reductases, we reconstruct efficient pathways for conversion of fatty acids to alkanes (0.8 mg l−1) and fatty alcohols (1.5 g l−1), to our knowledge the highest titres reported in S. cerevisiae. This should facilitate the construction of yeast cell factories for production of fatty acids derived products and even aldehyde-derived chemicals of high value. PMID:27222209

  16. Hydrolysis of tannic acid catalyzed by immobilized-stabilized derivatives of Tannase from Lactobacillus plantarum.

    PubMed

    Curiel, Jose Antonio; Betancor, Lorena; de las Rivas, Blanca; Muñoz, Rosario; Guisan, Jose M; Fernández-Lorente, Gloria

    2010-05-26

    A recombinant tannase from Lactobacillus plantarum , overexpressed in Escherichia coli , was purified in a single step by metal chelate affinity chromatography on poorly activated nickel supports. It was possible to obtain 0.9 g of a pure enzyme by using only 20 mL of chromatographic support. The pure enzyme was immobilized and stabilized by multipoint covalent immobilization on highly activated glyoxyl agarose. Derivatives obtained by multipoint and multisubunit immobilization were 500- and 1000-fold more stable than both the soluble enzyme and the one-point-immobilized enzyme in experiments of thermal and cosolvent inactivation, respectively. In addition, up to 70 mg of pure enzyme was immobilized on 1 g of wet support. The hydrolysis of tannic acid was optimized by using the new immobilized tannase derivative. The optimal reaction conditions were 30% diglyme at pH 5.0 and 4 degrees C. Under these conditions, it was possible to obtain 47.5 mM gallic acid from 5 mM tannic acid as substrate. The product was pure as proved by HPLC. On the other hand, the immobilized biocatalyst preserved >95% of its initial activity after 1 month of incubation under the optimal reaction conditions.

  17. Emerging roles of anacardic acid and its derivatives: a pharmacological overview.

    PubMed

    Hemshekhar, Mahadevappa; Sebastin Santhosh, Martin; Kemparaju, Kempaiah; Girish, Kesturu S

    2012-02-01

    Anacardic acid (AA) is a bioactive phytochemical found in nutshell of Anacardium occidentale. Chemically, it is a mixture of several closely related organic compounds, each consisting of salicylic acid substituted with an alkyl chain. The traditional Ayurveda depicts nutshell oil as a medicinal remedy for alexeritic, amebicidal, gingivitis, malaria and syphilitic ulcers. However, the enduring research and emerging evidence suggests that AA could be a potent target molecule with bactericide, fungicide, insecticide, anti-termite and molluscicide properties and as a therapeutic agent in the treatment of the most serious pathophysiological disorders like cancer, oxidative damage, inflammation and obesity. Furthermore, AA was found to be a common inhibitor of several clinically targeted enzymes such as NFκB kinase, histone acetyltransferase (HATs), lipoxygenase (LOX-1), xanthine oxidase, tyrosinase and ureases. In view of this, we have made an effort to summarize the ongoing research on the therapeutical role of AA and its derivatives. The current MiniReview sheds light on the pharmacological applications, toxicity and allergic responses associated with AA and its derivatives. Although the available records are promising, much more detailed investigations into the therapeutical properties, particularly the anti-cancer and anti-inflammatory activities, are urgently needed. We hope the present MiniReview will attract and encourage further research on elucidating and appreciating the possible curative properties of AA and its derivatives in the management of multifactorial diseases. PMID:22103711

  18. Inhibitory effects of gallic acid ester derivatives on Saccharomyces cerevisiae multidrug resistance protein Pdr5p.

    PubMed

    Pereira Rangel, Luciana; Fritzen, Márcio; Yunes, Rosendo Augusto; Leal, Paulo César; Creczynski-Pasa, Tânia Beatriz; Ferreira-Pereira, Antônio

    2010-05-01

    Overexpression of the Saccharomyces cerevisiae ABC transporter Pdr5p confers resistance to a range of structurally unrelated xenobiotics. This property allows Pdr5p to be used as a target for novel multidrug resistance reversal reagents or chemosensitizers. Herein, we report the effects of gallic acid derivatives with substitutions either on the ester moiety or in the benzene ring on the activity of Pdr5p. Compounds with a longer side chain (8-16 carbons) resulted in greater inhibition of Pdr5p ATPase. Derivatives with side chains of 8-12 carbons that retained hydroxyl groups on the benzene ring extensively inhibited Pdr5p ATPase activity. These compounds almost completely inhibited the efflux of the Pdr5p fluorescent substrate Rhodamine 6G and at 25 muM chemosensitized the Pdr5p-overexpressing strain AD124567 to fluconazole (0.4 mg mL(-1)). Gallic acid derivatives may be a new class of Pdr5p inhibitors.

  19. Hypolipidaemic and antiplatelet activity of phenoxyacetic acid derivatives related to alpha-asarone.

    PubMed

    Pérez-Pastén, Ricardo; García, Rosa Virginia; Garduño, Leticia; Reyes, Elba; Labarrios, Fernando; Tamariz, Joaquín; Chamorro, Germán

    2006-10-01

    The phenoxyacetic acid derivatives 1-6 [2-methoxy-4-(2-propenyl)phenoxyacetic acid (1); 2-methoxy-5-nitro-4-(2-propenyl)phenoxyacetic acid (2); methyl 2-methoxy-4-(2-propenyl)phenoxyacetate (3); ethyl 2-methoxy-4-(2-propenyl)phenoxyacetate (4); methyl 2-methoxy-5-nitro-4-(2-propenyl)phenoxyacetate (5); ethyl 2-methoxy-5-nitro-4-(2-propenyl)phenoxyacetate (6)] related to alpha-asarone have been reported previously as hypolipidaemic agents in diet-induced hyperlipidaemic mice. We have aimed to expand the pharmacological profile of these derivatives by investigating their hypolipidaemic activity in rats and mice under different experimental conditions. The antiplatelet activity was tested also in-vitro from blood derived from consenting healthy volunteers. In normolipidaemic rats, compounds 2, 3 and 5 at oral doses of 40 and 80 mg kg(-1) significantly decreased total cholesterol and LDL-cholesterol levels. Moreover, analogues 3 and 5 administered to hypercholesterolaemic rats at the same doses for seven days also produced a reduction in the content of these same lipoproteins. In neither case were the high-density lipoprotein cholesterol and triglyceride concentrations affected. However, practically all tested compounds were found to be hypocholesterolaemic agents, and were shown to effectively lower low-density lipoprotein cholesterol and triglyceride levels in Triton-induced hyperlipidaemic mice at oral doses of 50 and 100 mg kg(-1). In all tests, all animals appeared to be healthy throughout the experimental period in their therapeutic ranges. Triton-induced hypercholesterolaemic mice appeared to be a desirable model for this class of hypolipidaemic drugs. On the other hand, compounds 1, 2, 4 and 5 significantly inhibited ADP-induced aggregation in-vitro. These findings indicated that all of these compounds appeared to be promising for the treatment of human hyperlipidaemia and thrombotic diseases. PMID:17034657

  20. Cinnamic Acid Derivatives as Inhibitors of Oncogenic Protein Kinases--Structure, Mechanisms and Biomedical Effects.

    PubMed

    Mielecki, Marcin; Lesyng, Bogdan

    2016-01-01

    Cinnamic acid belongs to phenolic-acid class of polyphenols, one of the most abundant plant secondary metabolites. These substances are widely studied because of plethora of their biological activities. In particular, their inhibition of protein kinases contributes to the pleiotropic effects in the cell. Protein kinases are essential in controlling cell signaling networks. Selective targeting of oncogenic protein kinases increases clinical anticancer efficacy. Cinnamic acid and related compounds have inspired researchers in the design of numerous synthetic and semisynthetic inhibitors of oncogenic protein kinases for the past three decades. Interest in cinnamoyl-scaffold-containing compounds revived in recent years, which was stimulated by modern drug design and discovery methodologies such as in vitro and in silico HTS. This review presents cinnamic acid derivatives and analogs for which direct inhibition of protein kinases was identified. We also summarize significance of the above protein kinase families - validated or promising targets for anticancer therapies. The inhibition mode may vary from ATP-competitive, through bisubstrate-competitive and mixedcompetitive, to non-competitive one. Kinase selectivity is often correlated with subtle chemical modifications, and may also be steered by an additional non-cinnamoyl fragment of the inhibitor. Specific cinnamic acid congeners may synergize their effects in the cell by a wider range of activities, like suppression of additional enzymes, e.g. deubiquitinases, influencing the same signaling pathways (e.g. JAK2/STAT). Cinnamic acid, due to its biological and physicochemical properties, provides nature-inspired ideas leading to novel inhibitors of oncogenic protein kinases and related enzymes, capable to target a variety of cancer cells.

  1. Endiandric Acid Derivatives and Other Constituents of Plants from the Genera Beilschmiedia and Endiandra (Lauraceae)

    PubMed Central

    Ndjakou Lenta, Bruno; Chouna, Jean Rodolphe; Nkeng-Efouet, Pepin Alango; Sewald, Norbert

    2015-01-01

    Plants of the Lauraceae family are widely used in traditional medicine and are sources of various classes of secondary metabolites. Two genera of this family, Beilschmiedia and Endiandra, have been the subject of numerous investigations over the past decades because of their application in traditional medicine. They are the only source of bioactive endiandric acid derivatives. Noteworthy is that their biosynthesis contains two consecutive non-enzymatic electrocyclic reactions. Several interesting biological activities for this specific class of secondary metabolites and other constituents of the two genera have been reported, including antimicrobial, enzymes inhibitory and cytotoxic properties. This review compiles information on the structures of the compounds described between January 1960 and March 2015, their biological activities and information on endiandric acid biosynthesis, with 104 references being cited. PMID:26117852

  2. Synthesis of Aminoboronic Acid Derivatives from Amines and Amphoteric Boryl Carbonyl Compounds.

    PubMed

    Diaz, Diego B; Scully, Conor C G; Liew, Sean K; Adachi, Shinya; Trinchera, Piera; St Denis, Jeffrey D; Yudin, Andrei K

    2016-10-01

    Herein, we demonstrate the use of α-boryl aldehydes and acyl boronates in the synthesis of aminoboronic acid derivatives. This work highlights the untapped potential of boron-substituted iminium ions and offers insights into the behavior of N-methyliminodiacetyl (MIDA) boronates during condensation and tautomerization processes. The preparative value of this contribution lies in the demonstration that various amines, including linear and cyclic peptides, can be readily conjugated with boron-containing fragments. A mild deprotection of amino MIDA-boronates enables access to α- and β-aminoboronic acids in high chemical yields. This simple process should be applicable to the synthesis of a wide range of bioactive molecules as well as precursors for cross-coupling reactions. PMID:27584917

  3. Design, synthesis and antitumor activity of novel D-glucuronic acid derivatives.

    PubMed

    el-Nezhawy, Ahmed O H; Adly, Frady G; Eweas, Ahmed F; Hanna, Atef G; el-Kholy, Yehya M; el-Syed, Shahenaz H; el-Naggar, Tarek B A

    2011-11-01

    A series of D-glucuronic acid derivatives were chemically synthesized including acetylated and deacetylated glucuronamides, as well as N-glucuronides starting from the D-glucuronic acid itself by means of protection/deprotection, activation and condensation protocols. Structure elucidation of all products along with optimization of the synthetic steps is described. The synthesized compounds were evaluated for their in vitro antitumor activity against MCF-7, TK-10 and UACC-62 cell lines. The compounds 4, 5, 7, 8, 14, 16 and 18 were the most active against TK-10 cell line. On the other hand, the most active compounds against the MCF-7 cell line were 9, 18 and 20. However, compounds 7-10 13-15 and 17 were the most active against the UACC-62 cell line.

  4. Solvatochromic behavior of the electronic absorption spectra of gallic acid and some of its azo derivatives

    NASA Astrophysics Data System (ADS)

    Masoud, Mamdouh S.; Hagagg, Sawsan S.; Ali, Alaa E.; Nasr, Nessma M.

    The electronic absorption spectra of gallic acid and its azo derivatives have been studied in various solvents of different polarities. Multiple regression techniques were applied to calculate the regression and correlation coefficients based on an equation that relates the wavenumbers of the absorption band maxima (υmax-) to the solvent parameters; refractive index (n), dielectric constant (D), empirical Kamlet-Taft solvent parameters, π*(dipolarity/polarizability), α (solvent hydrogen-bond donor acidity) and β (solvent hydrogen-bond acceptor basicity). The fitting coefficient obtained from this analysis allows estimating the contribution of each type of interactions relative to total spectral shifts in solution. The dependence of υmax- on the solvent parameters indicates that the obtained bands are affected by specific and non-specific solute-solvent interactions.

  5. Solvatochromic behavior of the electronic absorption spectra of gallic acid and some of its azo derivatives.

    PubMed

    Masoud, Mamdouh S; Hagagg, Sawsan S; Ali, Alaa E; Nasr, Nessma M

    2012-08-01

    The electronic absorption spectra of gallic acid and its azo derivatives have been studied in various solvents of different polarities. Multiple regression techniques were applied to calculate the regression and correlation coefficients based on an equation that relates the wavenumbers of the absorption band maxima (υ(max)(-)) to the solvent parameters; refractive index (n), dielectric constant (D), empirical Kamlet-Taft solvent parameters, π*(dipolarity/polarizability), α (solvent hydrogen-bond donor acidity) and β (solvent hydrogen-bond acceptor basicity). The fitting coefficient obtained from this analysis allows estimating the contribution of each type of interactions relative to total spectral shifts in solution. The dependence of υ(max)(-) on the solvent parameters indicates that the obtained bands are affected by specific and non-specific solute-solvent interactions.

  6. Strecker degradation of amino acids promoted by a camphor-derived sulfonamide.

    PubMed

    Carvalho, M Fernanda N N; Ferreira, M João; Knittel, Ana S O; Oliveira, Maria da Conceição; Costa Pessoa, João; Herrmann, Rudolf; Wagner, Gabriele

    2016-01-01

    A camphor-derived sulfonimine with a conjugated carbonyl group, oxoimine 1 (O2SNC10H13O), reacts with amino acids (glycine, L-alanine, L-phenylalanine, L-leucine) to form a compound O2SNC10H13NC10H14NSO2 (2) which was characterized by spectroscopic means (MS and NMR) and supported by DFT calculations. The product, a single diastereoisomer, contains two oxoimine units connected by a -N= bridge, and thus has a structural analogy to the colored product Ruhemann´s purple obtained by the ninhydrin reaction with amino acids. A plausible reaction mechanism that involves zwitterions, a Strecker degradation of an intermediate imine and water-catalyzed tautomerizations was developed by means of DFT calculations on potential transition states. PMID:27340465

  7. Linoleic acid derivative DCP-LA improves learning impairment in SAMP8.

    PubMed

    Yaguchi, Takahiro; Nagata, Tetsu; Mukasa, Takeshi; Fujikawa, Hirokazu; Yamamoto, Hideyuki; Yamamoto, Satoshi; Iso, Hiroyuki; Tanaka, Akito; Nishizaki, Tomoyuki

    2006-01-23

    In the water-maze test, the linoleic acid derivative, 8-[2-(2-pentyl-cyclopropylmethyl)-cyclopropyl]-octanoic acid (DCP-LA) (1 mg/kg, intraperitoneally), significantly shortened the prolonged latency for accelerated-senescence-prone mice 8 (SAMP8), reaching a level similar to the latency for accelerated-senescence-resistant mice 1 (SAMR1) as control. In the open-field test to assess motor activity, it was confirmed that the DCP-LA effect is not due to increased motor activity. In the passive avoidance test to assess fear memory, DCP-LA had no effect on the latency of acquisition and retention for SAMP8. The results of the present study, thus, suggest that DCP-LA could improve age-related learning impairment by enhancing cognitive functions.

  8. Comparison of Dithiophosphinic and Phosphinic Acid Derivatives for Minor Actinide Extraction

    SciTech Connect

    Mason K Harrup; Dean R. Peterman; Thomas A. Luther; Mitchell R. Greenhalgh; John R. Klaehn

    2008-03-01

    A new extractant for the separation of actinide(III) and lanthanide(III), bis(otrifluoromethylphenyl) phosphinic acid (O-PA) was synthesized. The synthetic route employed mirrors one that was employed to produce the sulfur containing analog bis(otrifluoromethylphenyl) dithiophosphinic acid (S-PA). Multinuclear NMR spectroscopy was used for elementary characterization of the new O-PA derivative. This new O-PA extractant was used to perform Am(III)/Eu(III) separations and the results were directly compared to those obtained in identical separation experiments using S-PA, an extractant that is known to exhibit separation factors of ~100,000 at low pH. The separations data are presented and discussed in terms comparing the nature of the oxygen atom as a donor to that of the sulfur atom in extractants that are otherwise identical.

  9. Comparison of Aromatic Dithiophoshinic and Phosphinic Acid Derivatives for Minor Actinide Extraction

    SciTech Connect

    John R. Klaehn; Dean R. Peterman; Mason K. Harrup; Richard D. Tillotson; Mitchell R. Greenhalgh; Thomas A. Luther; Jack D. Law; Lee M. Daniels

    2008-03-01

    A new extractant for the separation of actinide(III) and lanthanide(III), bis(otrifluoromethylphenyl) phosphinic acid (O-PA) was synthesized. The synthetic route employed mirrors one that was employed to produce the sulfur containing analog bis(otrifluoromethylphenyl) dithiophosphinic acid (S-PA). Multinuclear NMR spectroscopy was used for elementary characterization of the new O-PA derivative. This new O-PA extractant was used to perform Am(III)/Eu(III) separations and the results were directly compared to those obtained in identical separation experiments using S-PA, an extractant that is known to exhibit separation factors of ~100,000 at low pH. The separations data are presented and discussed in terms comparing the nature of the oxygen atom as a donor to that of the sulfur atom in extractants that are otherwise identical.

  10. Amino-modified tetraphenylethene derivatives as nucleic acid stain: relationship between the structure and sensitivity.

    PubMed

    Xu, Li; Zhu, Zece; Wei, Danqing; Zhou, Xiang; Qin, Jingui; Yang, Chuluo

    2014-10-22

    A series of new amino-functionalized tetraphenylethene (TPE) derivatives were designed and synthesized to study the effect of molecular structures on the detection of nucleic acid. Contrastive studies revealed that the number of binding groups, the length of hydrophobic linking arm and the configuration of TPE molecule all play important roles on the sensitivity of the probes in nucleic acid detection. Z-TPE3 with two binding amino groups, long linking arms, and cis configuration was found to be the most sensitive dye in both solution and gel matrix. Z-TPE3 is able to stain dsDNA with the lowest amount of 1 ng and exclusively stain 40 ng of short oligonucleotide with only 10 nt. This work is of important significance for the further design of TPE probes as biosensors with higher sensitivity. PMID:25279446

  11. N-( p-Ethynylbenzoyl) derivatives of amino acid and dipeptide methyl esters - Synthesis and structural study

    NASA Astrophysics Data System (ADS)

    Eißmann, Frank; Weber, Edwin

    2011-11-01

    A series of N-( p-ethynylbenzoyl) derivatives ( 1-4) of the amino acids glycine and L-alanine as well as the dipeptides glycylglycine and L-alanylglycine has been synthesized via a two-step reaction sequence including the reaction of an appropriate N-( p-bromobenzoyl) precursor with trimethylsilylacetylene followed by deprotection of the trimethylsilyl protecting group, respectively. X-ray crystal structures of the amino acid and dipeptide methyl esters 1-4 are reported. The amide and peptide bonds within each molecular structure are planar and adopt the trans-configuration. The packing structures are governed by N sbnd H⋯O interactions leading to the formation of characteristic strand motifs. Further stabilization results from weaker C sbnd H⋯O and C sbnd H⋯π contacts.

  12. Hydrogels formed by enantioselective self-assembly of histidine-derived amphiphiles with tartaric acid.

    PubMed

    Zhang, Fanjun; Xu, Zhenghu; Dong, Shuli; Feng, Lei; Song, Aixin; Tung, Chen-Ho; Hao, Jingcheng

    2014-07-21

    Two chiral enantiomers of histidine-derived amphiphilic gelators, (4R,6S)-UIPCA and (4S,6R)-UIPCA, were synthesized through Pictet-Spengler reaction and their gelation behaviors with different organic acids were investigated. Interestingly, the chiral enantiomers of UIPCA showed smart enantioselectivity for gelating tartaric acid enantiomers to form hydrogels with excellent mechanical strength. The TEM and SEM images demonstrated that the hydrogels were composed of networks by physical entanglement of nanofibers with high aspect ratios. The formation of nanofibers was considered to be driven by the interplay of hydrogen bonding, electrostatic attraction, and hydrophobic interaction, which was supported by XRD and FT-IR spectra. The hydrogels exhibited sensitive response to a series of external stimuli, such as temperature, metal ions, and host-guest interactions, to realize the reversible gel-sol transition. The property of the gelation was elaborated and the gelators were expected to find their applications in chiral discrimination. PMID:24865976

  13. Chemical modulation of chaperone-mediated autophagy by retinoic acid derivatives

    PubMed Central

    Anguiano, Jaime; Garner, Thomas P; Mahalingam, Murugesan; Das, Bhaskar C.; Gavathiotis, Evripidis; Cuervo, Ana Maria

    2013-01-01

    Chaperone-mediated autophagy (CMA) contributes to cellular quality control and the cellular response to stress through the selective degradation of cytosolic proteins in lysosomes. Decrease in CMA activity occurs in aging and in age-related disorders (for example, neurodegenerative diseases and diabetes). Although prevention of this age-dependent decline through genetic manipulation in mouse has proven beneficial, chemical modulation of CMA is not currently possible, due in part to the lack of information on the signaling mechanisms that modulate this pathway. In this work, we report that signaling through the retinoic acid receptor alpha (RARα) inhibits CMA and apply structure-based chemical design to develop synthetic derivatives of all-trans-retinoic acid (ATRA) to specifically neutralize this inhibitory effect. We demonstrate that chemical enhancement of CMA protects cells from oxidative stress and from proteotoxicity, supporting a potential therapeutic opportunity when reduced CMA contributes to cellular dysfunction and disease. PMID:23584676

  14. Strecker degradation of amino acids promoted by a camphor-derived sulfonamide

    PubMed Central

    Ferreira, M João; Knittel, Ana S O; Oliveira, Maria da Conceição; Costa Pessoa, João; Herrmann, Rudolf; Wagner, Gabriele

    2016-01-01

    Summary A camphor-derived sulfonimine with a conjugated carbonyl group, oxoimine 1 (O2SNC10H13O), reacts with amino acids (glycine, L-alanine, L-phenylalanine, L-leucine) to form a compound O2SNC10H13NC10H14NSO2 (2) which was characterized by spectroscopic means (MS and NMR) and supported by DFT calculations. The product, a single diastereoisomer, contains two oxoimine units connected by a –N= bridge, and thus has a structural analogy to the colored product Ruhemann´s purple obtained by the ninhydrin reaction with amino acids. A plausible reaction mechanism that involves zwitterions, a Strecker degradation of an intermediate imine and water-catalyzed tautomerizations was developed by means of DFT calculations on potential transition states. PMID:27340465

  15. Arachidonic Acid Derivatives and Their Role in Peripheral Nerve Degeneration and Regeneration

    PubMed Central

    Camara-Lemarroy, Carlos Rodrigo; Gonzalez-Moreno, Emmanuel Irineo; Guzman-de la Garza, Francisco Javier; Fernandez-Garza, Nancy Esthela

    2012-01-01

    After peripheral nerve injury, a process of axonal degradation, debris clearance, and subsequent regeneration is initiated by complex local signaling, called Wallerian degeneration (WD). This process is in part mediated by neuroglia as well as infiltrating inflammatory cells and regulated by inflammatory mediators such as cytokines, chemokines, and the activation of transcription factors also related to the inflammatory response. Part of this neuroimmune signaling is mediated by the innate immune system, including arachidonic acid (AA) derivatives such as prostaglandins and leukotrienes. The enzymes responsible for their production, cyclooxygenases and lipooxygenases, also participate in nerve degeneration and regeneration. The interactions between signals for nerve regeneration and neuroinflammation go all the way down to the molecular level. In this paper, we discuss the role that AA derivatives might play during WD and nerve regeneration, and the therapeutic possibilities that arise. PMID:22997489

  16. Evolution in medicinal chemistry of ursolic acid derivatives as anticancer agents.

    PubMed

    Chen, Haijun; Gao, Yu; Wang, Ailan; Zhou, Xiaobin; Zheng, Yunquan; Zhou, Jia

    2015-03-01

    Currently, there is a renewed interest in common dietaries and plant-based traditional medicines for the prevention and treatment of cancer. In the search for potential anticancer agents from natural sources, ursolic acid (UA), a pentacyclic triterpenoid widely found in various medicinal herbs and fruits, exhibits powerful biological effects including its attractive anticancer activity against various types of cancer cells. However, the limited solubility, rapid metabolism and poor bioavailability of UA restricted its further clinical applications. In the past decade, with substantial progress toward the development of new chemical entities for the treatment of cancer, numerous UA derivatives have been designed and prepared to overcome its disadvantages. Despite extensive effort, discovery of effective UA derivatives has so far met with only limited success. This review summarizes the current status of the structural diversity and evolution in medicinal chemistry of UA analogues and provides a detailed discussion of future direction for further research in the chemical modifications of UA.

  17. Docking analysis of gallic acid derivatives as HIV-1 protease inhibitors.

    PubMed

    Singh, Anjali; Pal, Tapan Kumar

    2015-01-01

    HIV-1 Protease (HIV-1 PR) enzymes are essential for accurate assembly and maturation of infectious HIV retroviruses. The significant role of HIV-1 protease in viral replication has made it a potential drug target. In the recent past, phytochemical Gallic Acid (GA) derivatives have been screened for protease inhibitor activity. The present work aims to design and evaluate potential GA-based HIV-1 PR phytoinhibitors by docking approach. The ligands were prepared by ChemDraw and docking was performed in HEX software. In this present study, one of the GA analogues (GA4) emerged as a potent drug candidate for HIV-1 PR inhibition, and docking results showed it to be comparable with anti-HIV drugs, darunavir and amprenavir. The GA4 derivative provided a lead for designing more effective HIV-1 PR inhibitors.

  18. Controlled synthesis and inclusion ability of a hyaluronic acid derivative bearing beta-cyclodextrin molecules.

    PubMed

    Charlot, Aurélia; Heyraud, Alain; Guenot, Pierre; Rinaudo, Marguerite; Auzély-Velty, Rachel

    2006-03-01

    A new synthetic route to beta-cyclodextrin-linked hyaluronic acid (HA-CD) was developed. This was based on the preparation of a HA derivative selectively modified with adipic dihydrazide (HA-ADH) and a beta-cyclodextrin derivative possessing an aldehyde function on the primary face, followed by their coupling by a reductive amination-type reaction. The CD-polysaccharide was fully characterized in terms of chemical integrity and purity by high-resolution NMR spectroscopy. The complexation ability of the grafted CD was further demonstrated by isothermal titration calorimetry using sodium adamantane acetate (ADAc) and Ibuprofen as model guest molecules. The thermodynamic parameters for the complexation of these negatively charged guest molecules by the beta-CD grafted on negatively charged HA were shown to be largely influenced by the ionic strength of the aqueous medium. PMID:16529430

  19. Lysophosphatidic acid acts as a nutrient-derived developmental cue to regulate early hematopoiesis

    PubMed Central

    Li, Haisen; Yue, Rui; Wei, Bin; Gao, Ge; Du, Jiulin; Pei, Gang

    2014-01-01

    Primitive hematopoiesis occurs in the yolk sac blood islands during vertebrate embryogenesis, where abundant phosphatidylcholines (PC) are available as important nutrients for the developing embryo. However, whether these phospholipids also generate developmental cues to promote hematopoiesis is largely unknown. Here, we show that lysophosphatidic acid (LPA), a signaling molecule derived from PC, regulated hemangioblast formation and primitive hematopoiesis. Pharmacological and genetic blockage of LPA receptor 1 (LPAR1) or autotoxin (ATX), a secretory lysophospholipase that catalyzes LPA production, inhibited hematopoietic differentiation of mouse embryonic stem cells and impaired the formation of hemangioblasts. Mechanistic experiments revealed that the regulatory effect of ATX-LPA signaling was mediated by PI3K/Akt-Smad pathway. Furthermore, during in vivo embryogenesis in zebrafish, LPA functioned as a developmental cue for hemangioblast formation and primitive hematopoiesis. Taken together, we identified LPA as an important nutrient-derived developmental cue for primitive hematopoiesis as well as a novel mechanism of hemangioblast regulation. PMID:24829209

  20. Production of fumaric acid from biodiesel-derived crude glycerol by Rhizopus arrhizus.

    PubMed

    Zhou, Yuqing; Nie, Kaili; Zhang, Xin; Liu, Shihong; Wang, Meng; Deng, Li; Wang, Fang; Tan, Tianwei

    2014-07-01

    This work investigated the capability of Rhizopus arrhizus to assimilate biodiesel-derived crude glycerol and convert it into fumaric acid. After optimizing the initial glycerol concentration, spore inoculum and yeast extract concentration, smaller pellets (0.7 mm) and higher biomass (3.11 g/L) were obtained when R. arrhizus grew on crude glycerol. It was found that crude glycerol was more suitable than glucose for smaller R. arrhizus pellet forming. When 80 g/L crude glycerol was used as carbon source, the fumaric acid production of 4.37 g/L was obtained at 192 h. With a highest concentration of 22.81 g/L achieved in the co-fermentation of crude glycerol (40 g/L) and glucose (40 g/L) at 144 h, the fumaric acid production was enhanced by 553.6%, compared to the fermentation using glycerol (80 g/L) as sole carbon source. Moreover, the production cost of fumaric acid in co-fermentation was reduced by approximately 14% compared to glucose fermentation. PMID:24787316

  1. Metformin inhibits Branched Chain Amino Acid (BCAA) derived ketoacidosis and promotes metabolic homeostasis in MSUD

    PubMed Central

    S. Sonnet, Davis; N. O’Leary, Monique; A. Gutierrez, Mark; M. Nguyen, Steven; Mateen, Samiha; Hsu, Yuehmei; P. Mitchell, Kylie; J. Lopez, Antonio; Vockley, Jerry; K. Kennedy, Brian; Ramanathan, Arvind

    2016-01-01

    Maple Syrup Urine Disease (MSUD) is an inherited disorder caused by the dysfunction in the branched chain keto-acid dehydrogenase (BCKDH) enzyme. This leads to buildup of branched-chain keto-acids (BCKA) and branched-chain amino acids (BCAA) in body fluids (e.g. keto-isocaproic acid from the BCAA leucine), leading to numerous clinical features including a less understood skeletal muscle dysfunction in patients. KIC is an inhibitor of mitochondrial function at disease relevant concentrations. A murine model of intermediate MSUD (iMSUD) shows significant skeletal muscle dysfunction as by judged decreased muscle fiber diameter. MSUD is an orphan disease with a need for novel drug interventions. Here using a 96-well plate (liquid chromatography- mass spectrometry (LC-MS) based drug-screening platform we show that Metformin, a widely used anti-diabetic drug, reduces levels of KIC in patient-derived fibroblasts by 20–50%. This Metformin-mediated effect was conserved in vivo; Metformin-treatment significantly reduced levels of KIC in the muscle (by 69%) and serum (by 56%) isolated from iMSUD mice, and restored levels of mitochondrial metabolites (e.g. AMP and other TCA). The drug also decreased the expression of mitochondrial branched chain amino transferase (BCAT) which produces KIC in skeletal muscle. This suggests that Metformin can restore skeletal muscle homeostasis in MSUD by decreasing mitochondrial KIC production. PMID:27373929

  2. Uptake of acidic and basic sugar derivatives in Lemna gibba G1

    SciTech Connect

    Sanz, A.; Ullrich, C.I. Institut fuer Botanik, Darmstadt )

    1989-08-01

    The uptake of acidic and basic sugar derivatives in Lemna gibba L. was studied. Uronic acids applied to the experimental solution induced a small decrease of the membrane potential. After incubation of the plants in a 0.1 millimolar solution of these substrates, no decrease in the concentration of reducing groups in the external solution was detected. Respiration increased by 31% with 50 millimolar galacturonic acid, whereas no effect was found with the same concentration of glucuronic acid. Glucosamine caused a considerable concentration-dependent membrane depolarization. ({sup 14}C)glucosamine uptake followed Michaelis-Menten kinetics together with a linear component. Influx of this substrate was inhibited by glucose but the type of competition could not be clearly distinguished. Glucosamine, 50 millimolar, inhibited the respiration rate by 30%. The glucosamine uptake was pH-dependent, with maximum uptake at around pH 7. Lack of enhancement of uptake by low pH as well as the permanent membrane depolarization suggest a uniport mechanism for the charged species of the substrate and an electroneutral diffusion of the uncharged species.

  3. Recent progress in electrochemical biosensors based on phenylboronic acid and derivatives.

    PubMed

    Anzai, Jun-Ichi

    2016-10-01

    This review provides an overview of recent progress made in the development of electrochemical biosensors based on phenylboronic acid (PBA) and its derivatives. PBAs are known to selectively bind 1,2- and 1,3-diols to form negatively charged boronate esters in neutral aqueous media and have been used to construct electrochemical glucose sensors because of this selective binding. PBA-modified metal and carbon electrodes have been widely studied as voltammetric and potentiometric glucose sensors. In some cases, ferroceneboronic acid or ferrocene-modified phenylboronic acids are used as sugar-selective redox compounds. Another option for sensors using PBA-modified electrodes is potentiometric detection, in which the changes in surface potential of the electrodes are detected as an output signal. An ion-sensitive field effect transistor (FET) has been used as a signal transducer in potentiometric sensors. Glycoproteins, such as glycated hemoglobin (HbA1c), avidin, and serum albumin can also be detected by PBA-modified electrodes because they contain hydrocarbon chains on the surface. HbA1c sensors are promising alternatives to enzyme-based glucose sensors for monitoring blood glucose levels over the preceding 2-3months. In addition, PBA-modified electrodes can be used to detect a variety of compounds including hydroxy acids and fluoride (F(-)) ions. PBA-based F(-) ion sensors may be useful if reagentless sensors can be developed.

  4. Modification of nucleic acids by azobenzene derivatives and their applications in biotechnology and nanotechnology.

    PubMed

    Li, Jing; Wang, Xingyu; Liang, Xingguo

    2014-12-01

    Azobenzene has been widely used as a photoregulator due to its reversible photoisomerization, large structural change between E and Z isomers, high photoisomerization yield, and high chemical stability. On the other hand, some azobenzene derivatives can be used as universal quenchers for many fluorophores. Nucleic acid is a good candidate to be modified because it is not only the template of gene expression but also widely used for building well-organized nanostructures and nanodevices. Because the size and polarity distribution of the azobenzene molecule is similar to a nucleobase pair, the introduction of azobenzene into nucleic acids has been shown to be an ingenious molecular design for constructing light-switching biosystems or light-driven nanomachines. Here we review recent advances in azobenzene-modified nucleic acids and their applications for artificial regulation of gene expression and enzymatic reactions, construction of photoresponsive nanostructures and nanodevices, molecular beacons, as well as obtaining structural information using the introduced azobenzene as an internal probe. In particular, nucleic acids bearing multiple azobenzenes can be used as a novel artificial nanomaterial with merits of high sequence specificity, regular duplex structure, and high photoregulation efficiency. The combination of functional groups with biomolecules may further advance the development of chemical biotechnology and biomolecular engineering.

  5. Recent progress in electrochemical biosensors based on phenylboronic acid and derivatives.

    PubMed

    Anzai, Jun-Ichi

    2016-10-01

    This review provides an overview of recent progress made in the development of electrochemical biosensors based on phenylboronic acid (PBA) and its derivatives. PBAs are known to selectively bind 1,2- and 1,3-diols to form negatively charged boronate esters in neutral aqueous media and have been used to construct electrochemical glucose sensors because of this selective binding. PBA-modified metal and carbon electrodes have been widely studied as voltammetric and potentiometric glucose sensors. In some cases, ferroceneboronic acid or ferrocene-modified phenylboronic acids are used as sugar-selective redox compounds. Another option for sensors using PBA-modified electrodes is potentiometric detection, in which the changes in surface potential of the electrodes are detected as an output signal. An ion-sensitive field effect transistor (FET) has been used as a signal transducer in potentiometric sensors. Glycoproteins, such as glycated hemoglobin (HbA1c), avidin, and serum albumin can also be detected by PBA-modified electrodes because they contain hydrocarbon chains on the surface. HbA1c sensors are promising alternatives to enzyme-based glucose sensors for monitoring blood glucose levels over the preceding 2-3months. In addition, PBA-modified electrodes can be used to detect a variety of compounds including hydroxy acids and fluoride (F(-)) ions. PBA-based F(-) ion sensors may be useful if reagentless sensors can be developed. PMID:27287174

  6. Metformin inhibits Branched Chain Amino Acid (BCAA) derived ketoacidosis and promotes metabolic homeostasis in MSUD.

    PubMed

    S Sonnet, Davis; N O'Leary, Monique; A Gutierrez, Mark; M Nguyen, Steven; Mateen, Samiha; Hsu, Yuehmei; P Mitchell, Kylie; J Lopez, Antonio; Vockley, Jerry; K Kennedy, Brian; Ramanathan, Arvind

    2016-01-01

    Maple Syrup Urine Disease (MSUD) is an inherited disorder caused by the dysfunction in the branched chain keto-acid dehydrogenase (BCKDH) enzyme. This leads to buildup of branched-chain keto-acids (BCKA) and branched-chain amino acids (BCAA) in body fluids (e.g. keto-isocaproic acid from the BCAA leucine), leading to numerous clinical features including a less understood skeletal muscle dysfunction in patients. KIC is an inhibitor of mitochondrial function at disease relevant concentrations. A murine model of intermediate MSUD (iMSUD) shows significant skeletal muscle dysfunction as by judged decreased muscle fiber diameter. MSUD is an orphan disease with a need for novel drug interventions. Here using a 96-well plate (liquid chromatography- mass spectrometry (LC-MS) based drug-screening platform we show that Metformin, a widely used anti-diabetic drug, reduces levels of KIC in patient-derived fibroblasts by 20-50%. This Metformin-mediated effect was conserved in vivo; Metformin-treatment significantly reduced levels of KIC in the muscle (by 69%) and serum (by 56%) isolated from iMSUD mice, and restored levels of mitochondrial metabolites (e.g. AMP and other TCA). The drug also decreased the expression of mitochondrial branched chain amino transferase (BCAT) which produces KIC in skeletal muscle. This suggests that Metformin can restore skeletal muscle homeostasis in MSUD by decreasing mitochondrial KIC production. PMID:27373929

  7. Green Synthesis and Urease Inhibitory Activity of Spiro-Pyrimidinethiones/Spiro-Pyrimidinones-Barbituric Acid Derivatives

    PubMed Central

    Mohammadi Ziarani, Ghodsi; Asadi, Shima; Faramarzi, Sakineh; Amanlou, Massoud

    2015-01-01

    Sulfonic acid functionalized SBA-15 (SBA-Pr-SO3H) with pore size 6 nm as an efficient heterogeneous nanoporous solid acid catalyst exhibited good catalytic activity in the Biginelli-like reaction in the synthesis of spiroheterobicyclic rings with good yield and good recyclability. Spiro-pyrimidinethiones/spiro-pyrimidinones-barbituric acid derivatives were synthesized in a simple and efficient method using the one-pot three-component reaction of a cyclic 1,3- dicarbonyl compounds (barbituric acid), an aromatic aldehyde and urea or thiourea in the presence of nanoporous silica SBA-Pr-SO3H under solvent free conditions. Urease inhibitory activity of spiro compounds were tested against Jack bean urease using Berthelot alkaline phenol–hypochlorite method. Five of 13 compounds were inhibitor and two of them were enzyme activators. Analysis of the docking results showed that, in most of the spiro molecules, one of the carbonyl groups is coordinated with both nickel atoms, while the other one is involved in the formation of hydrogen bonds with important active-site residues. The effect of inserting two methyl groups on N atoms of barbiturate ring, S substituted, ortho, meta and para substituted compounds were investigated too. PMID:26664377

  8. Derivation of fixed partial charges for amino acids accommodating a specific water model and implicit polarization.

    PubMed

    Cerutti, David S; Rice, Julia E; Swope, William C; Case, David A

    2013-02-28

    We have developed the IPolQ method for fitting nonpolarizable point charges to implicitly represent the energy of polarization for systems in pure water. The method involves iterative cycles of molecular dynamics simulations to estimate the water charge density around the solute of interest, followed by quantum mechanical calculations at the MP2/cc-pV(T+d)Z level to determine updated solute charges. Lennard-Jones parameters are updated starting from the Amber FF99SB nonbonded parameter set to accommodate the new charge model, guided by the comparisons to experimental hydration free energies (HFEs) of neutral amino acid side chain analogs and assumptions about the computed HFEs for charged side chains. These Lennard-Jones parameter adjustments for side-chain analogs are assumed to be transferable to amino acids generally, and new charges for all standard amino acids are then derived in the presence of water modeled by TIP4P-Ew. Overall, the new charges depict substantially more polarized amino acids, particularly in the backbone moieties, than previous Amber charge sets. Efforts to complete a new force field with appropriate torsion parameters for this charge model are underway. The IPolQ method is general and applicable to arbitrary solutes.

  9. Synthesis and biological activity of arylspiroborate salts derived from caffeic Acid phenethyl ester.

    PubMed

    Hébert, Martin J G; Flewelling, Andrew J; Clark, Trevor N; Levesque, Natalie A; Jean-François, Jacques; Surette, Marc E; Gray, Christopher A; Vogels, Christopher M; Touaibia, Mohamed; Westcott, Stephen A

    2015-01-01

    Two novel boron compounds containing caffeic acid phenethyl ester (CAPE) derivatives have been prepared and characterized fully. These new compounds and CAPE have been investigated for potential antioxidant and antimicrobial properties and their ability to inhibit 5-lipoxygenase and whether chelation to boron improves their biological activity. Sodium salt 4 was generally more active than ammonium salt 5 in the biological assays and surpassed the radical scavenging ability of CAPE. Compounds 4 and 5 were more active than CAPE and Zileuton in human polymorphonuclear leukocytes. These results clearly show the effectiveness of the synthesized salts as transporter of CAPE. PMID:25834744

  10. Synthesis and Biological Activity of Arylspiroborate Salts Derived from Caffeic Acid Phenethyl Ester

    PubMed Central

    Hébert, Martin J. G.; Flewelling, Andrew J.; Clark, Trevor N.; Jean-François, Jacques; Surette, Marc E.; Gray, Christopher A.; Vogels, Christopher M.; Touaibia, Mohamed; Westcott, Stephen A.

    2015-01-01

    Two novel boron compounds containing caffeic acid phenethyl ester (CAPE) derivatives have been prepared and characterized fully. These new compounds and CAPE have been investigated for potential antioxidant and antimicrobial properties and their ability to inhibit 5-lipoxygenase and whether chelation to boron improves their biological activity. Sodium salt 4 was generally more active than ammonium salt 5 in the biological assays and surpassed the radical scavenging ability of CAPE. Compounds 4 and 5 were more active than CAPE and Zileuton in human polymorphonuclear leukocytes. These results clearly show the effectiveness of the synthesized salts as transporter of CAPE. PMID:25834744

  11. Metal-organic frameworks constructed from crown ether-based 1,4-benzenedicarboxylic acid derivatives.

    PubMed

    Chen, Teng-Hao; Schneemann, Andreas; Fischer, Roland A; Cohen, Seth M

    2016-02-21

    A series of unprecedented crown ether- and thiacrown ether-derivatized benzene dicarboxylic acid (H2bdc) ligands has been synthesized and incorporated into the prototypical isoreticular metal-organic framework (IRMOF) and UiO-66 materials. In the case of UiO-66, only MOFs comprised from a mixed-ligand composition, requiring both unsubstituted bdc and crown ether containing ligands, could be prepared. These are among the few ligand derivatives, and resulting MOFs, that incorporate a macrocyclic group directly on the bdc ligand, providing a new, modular platform for exploring new supramolecular and coordination chemistry within MOFs.

  12. New lipophilic piceatannol derivatives exhibiting antioxidant activity prepared by aromatic hydroxylation with 2-iodoxybenzoic acid (IBX).

    PubMed

    Bernini, Roberta; Barontini, Maurizio; Spatafora, Carmela

    2009-01-01

    Piceatannol (E-3,5,3',4'-tetrahydroxystilbene) is a phytoalexin synthesized in grapes in response to stress conditions. It exhibits strong antioxidant and antileukaemic activities due to the presence of the catechol moiety. To modify some physical properties like solubility, and miscibility in non-aqueous media some new previously unreported piceatannol derivatives having lipophilic chains on the A-ring were prepared in good yields by a simple and efficient procedure. The key step was a chemo- and regioselective aromatic hydroxylation with 2-iodoxybenzoic acid (IBX). The new compounds showed antioxidant activity and seemed promising for possible applications as multifunctional emulsifiers in food, cosmetic and pharmaceutical fields.

  13. Antitumor Mechanisms of Amino Acid Hydroxyurea Derivatives in the Metastatic Colon Cancer Model

    PubMed Central

    Šaban, Nina; Stepanić, Višnja; Vučinić, Srđan; Horvatić, Anita; Cindrić, Mario; Perković, Ivana; Zorc, Branka; Oršolić, Nada; Mintas, Mladen; Pavelić, Krešimir; Pavelić, Sandra Kraljević

    2013-01-01

    The paper presents a detailed study of the biological effects of two amino acid hydroxyurea derivatives that showed selective antiproliferative effects in vitro on the growth of human tumor cell line SW620. Tested compounds induced cell cycle perturbations and apoptosis. Proteins were identified by proteomics analyses using two-dimensional gel electrophoresis coupled to mass spectrometry, which provided a complete insight into the most probable mechanism of action on the protein level. Molecular targets for tested compounds were analyzed by cheminformatics tools. Zinc-dependent histone deacetylases were identified as potential targets responsible for the observed antiproliferative effect. PMID:24304540

  14. Antitumor mechanisms of amino Acid hydroxyurea derivatives in the metastatic colon cancer model.

    PubMed

    Saban, Nina; Stepanić, Višnja; Vučinić, Srđan; Horvatić, Anita; Cindrić, Mario; Perković, Ivana; Zorc, Branka; Oršolić, Nada; Mintas, Mladen; Pavelić, Krešimir; Pavelić, Sandra Kraljević

    2013-01-01

    The paper presents a detailed study of the biological effects of two amino acid hydroxyurea derivatives that showed selective antiproliferative effects in vitro on the growth of human tumor cell line SW620. Tested compounds induced cell cycle perturbations and apoptosis. Proteins were identified by proteomics analyses using two-dimensional gel electrophoresis coupled to mass spectrometry, which provided a complete insight into the most probable mechanism of action on the protein level. Molecular targets for tested compounds were analyzed by cheminformatics tools. Zinc-dependent histone deacetylases were identified as potential targets responsible for the observed antiproliferative effect.

  15. Evaluation of synthetic naphthalene derivatives as novel chemical chaperones that mimic 4-phenylbutyric acid.

    PubMed

    Mimori, Seisuke; Koshikawa, Yukari; Mashima, Yu; Mitsunaga, Katsuyoshi; Kawada, Koichi; Kaneko, Masayuki; Okuma, Yasunobu; Nomura, Yasuyuki; Murakami, Yasuoki; Kanzaki, Tetsuto; Hamana, Hiroshi

    2015-02-15

    The chemical chaperone 4-phenylbutyric acid (4-PBA) has potential as an agent for the treatment of neurodegenerative diseases. However, the requirement of high concentrations warrants chemical optimization for clinical use. In this study, novel naphthalene derivatives with a greater chemical chaperone activity than 4-PBA were synthesized with analogy to the benzene ring. All novel compounds showed chemical chaperone activity, and 2 and 5 possessed high activity. In subsequent experiments, the protective effects of the compounds were examined in Parkinson's disease model cells, and low toxicity of 9 and 11 was related to amphiphilic substitution with naphthalene.

  16. Metal-organic frameworks constructed from crown ether-based 1,4-benzenedicarboxylic acid derivatives.

    PubMed

    Chen, Teng-Hao; Schneemann, Andreas; Fischer, Roland A; Cohen, Seth M

    2016-02-21

    A series of unprecedented crown ether- and thiacrown ether-derivatized benzene dicarboxylic acid (H2bdc) ligands has been synthesized and incorporated into the prototypical isoreticular metal-organic framework (IRMOF) and UiO-66 materials. In the case of UiO-66, only MOFs comprised from a mixed-ligand composition, requiring both unsubstituted bdc and crown ether containing ligands, could be prepared. These are among the few ligand derivatives, and resulting MOFs, that incorporate a macrocyclic group directly on the bdc ligand, providing a new, modular platform for exploring new supramolecular and coordination chemistry within MOFs. PMID:26765588

  17. Dehydroabietic Acid Derivative QC4 Induces Gastric Cancer Cell Death via Oncosis and Apoptosis

    PubMed Central

    Luo, Dongjun; Ni, Qing; Ji, Anlai; Gu, Wen; Wu, Junhua

    2016-01-01

    Aim. QC4 is the derivative of rosin's main components dehydroabietic acid (DHA). We investigated the cytotoxic effect of QC4 on gastric cancer cells and revealed the mechanisms beneath the induction of cell death. Methods. The cytotoxic effect of QC4 on gastric cancer cells was evaluated by CCK-8 assay and flow cytometry. The underlying mechanisms were tested by administration of cell death related inhibitors and detection of apoptotic and oncosis related proteins. Cytomembrane integrity and organelles damage were confirmed by lactate dehydrogenase (LDH) leakage assay, mitochondrial function test, and cytosolic free Ca2+ concentration detection. Results. QC4 inhibited cell proliferation dose- and time-dependently and destroyed cell membrane integrity, activated calpain-1 autolysis, and induced apoptotic protein cleavage in gastric cancer cells. The detection of decreased ATP and mitochondrial membrane potential, ROS accumulation, and cytosolic free Ca2+ elevation confirmed organelles damage in QC4-treated gastric cancer cells. Conclusions. DHA derivative QC4 induced the damage of cytomembrane and organelles which finally lead to oncosis and apoptosis in gastric cancer cells. Therefore, as a derivative of plant derived small molecule DHA, QC4 might become a promising agent in gastric cancer therapy. PMID:27057539

  18. Aquatic predicted no-effect-concentration derivation for perfluorooctane sulfonic acid.

    PubMed

    Qi, Ping; Wang, Ying; Mu, Jingli; Wang, Juying

    2011-04-01

    Perfluorooctane sulfonic acid (PFOS), a representative perfluorinated surfactant, is an anthropogenic pollutant detected in various environmental and biological matrices. Some laboratory and field work has been conducted to assess the aquatic toxicity of PFOS, but little is known regarding its toxicity threshold to the aquatic ecosystem. In the present study, predicted no-effect concentrations (PNECs) were derived by four different approaches. The interspecies correlation estimation (ICE) program and final acute-to-chronic ratio (FACR) were applied to the development of PNEC based on the toxic mode of action (MOA) of PFOS. By comparison of the different PNECs, the recommended aquatic toxicity thresholds for PFOS are in the range of 0.61 to 6.66 µg/L. Based on comparison of PNEC values, microcosm results, and reported environmental concentrations, PFOS appears not to pose a serious threat to aquatic organisms. The present results demonstrate that MOA is an important consideration for the derivation of reliable PNECs; moreover, the ICE-based species sensitivity distribution (SSD) method can be used to derive PNECs when toxicological data are limited. The application of MOA and ICE for deriving PNEC values in the present study may facilitate studies on using a combination of quantitative structure-activity relationship (QSAR) models and ICE to estimate PNECs.

  19. The marine sponge-derived polyketide endoperoxide plakortide F acid mediates its antifungal activity by interfering with calcium homeostasis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Plakortide F acid (PFA) is a marine-derived polyketide endoperoxide exhibiting strong inhibitory activity against several clinically important fungal pathogens. In the present study, transcriptional profiling coupled with mutant and biochemical analyses were conducted using the model organism Sacch...

  20. Quantitation of flavanols, proanthocyanidins, isoflavones, flavanones, dihydrochalcones, stilbenes, and benzoic Acid derivatives after identification by LC-MS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A general method was developed for the systematic quantitation of catechins, proanthocyanidins, isoflavones, flavanones, dihydrochalcones, stilbenes, and hydroxybenzoic acid derivatives (mainly hydrolyzable tannins) using the UV relative mole response factors (MRRF) of the reference standard from ea...

  1. Isolation, modification, and aldose reductase inhibitory activity of rosmarinic acid derivatives from the roots of Salvia grandifolia.

    PubMed

    Kang, Jie; Tang, Yanbo; Liu, Quan; Guo, Nan; Zhang, Jian; Xiao, Zhiyan; Chen, Ruoyun; Shen, Zhufang

    2016-07-01

    To find aldose reductase inhibitors, two previously unreported compounds, grandifolias H and I, and five known compounds, including rosmarinic acid and rosmarinic acid derivatives, were isolated from the roots of Salvia grandifolia. A series of rosmarinic acid derivatives was obtained from rosmarinic acid using simple synthetic methods. The aldose reductase inhibitory activity of the isolated and synthesized compounds was assessed. Seven of the tested compounds showed moderate aldose reductase inhibition (IC50=0.06-0.30μM). The structure-activity relationship of aldose reductase inhibitory activity of rosmarinic acid derivatives was discussed for the first time. This study provided useful information that will facilitate the development of aldose reductase inhibitors. PMID:27233987

  2. Synthesis and biological activity of 3-[phenyl(1,3-thiazol-2-yl)-amino]propanoic acids and their derivatives.

    PubMed

    Mickevičius, Vytautas; Voskienė, Aušra; Jonuškienė, Ilona; Kolosej, Ramūnė; Šiugždaitė, Jūratė; Venskutonis, Petras Rimantas; Kazernavičiūtė, Rita; Brazienė, Zita; Jakienė, Elena

    2013-01-01

    New N,N-disubstituted β-amino acids and their derivatives with thiazole, aromatic, and heterocyclic substituents were synthesized from N-phenyl-N-thiocarbamoyl-β-alanine by the Hantzsch method; derivatives with hydrazone fragments were also obtained. Some of the synthesized compounds exhibited discrete antimicrobial activity, and 3-[(4-oxo-4,5-dihydro-1,3-thiazol-2-yl)(phenyl)amino]propanoic acid was found to promote rapeseed growth and to increase seed yield and oil content.

  3. [Study of pantothenic acid derivatives as cardiac protectors in a model of experimental ischemia and reperfusion of the isolated heart].

    PubMed

    Kumerova, A O; Utno, L Ia; Lipsberga, Z E; Shkestere, I Ia

    1992-04-01

    An isolated heart model with experimental ischemia and reperfusion was used to show effective decrease in lactate, increase in ATP content and prevention of conjugated dienes accumulation in the myocardium by derivatives of pantothenic acid: panthenol (9.0 mg/kg), calcium pantothenate (15.6 mg/kg) and by these ones applied simultaneously as ingredients of perfusate (25 microM) in postischemic period. In that way derivatives of pantothenic acid should be regarded as cardiac protectors. PMID:1391892

  4. Microbial synthesis of polyhydroxyalkanoate using seaweed-derived crude levulinic acid as co-nutrient.

    PubMed

    Bera, Anupam; Dubey, Sonam; Bhayani, Khushbu; Mondal, Dibyendu; Mishra, Sandhya; Ghosh, Pushpito K

    2015-01-01

    Production of polyhydroxyalkanoates (PHAs) from Jatropha biodiesel residues, namely crude glycerol and oil cake hydrolysate, has been reported previously. Halomonas hydrothermalis (MTCC accession no. 5445; NCBI Genbank accession no. GU938192), a wild marine strain, was used in the bio-synthesis. The present study was initiated to vary the properties of the polymer. Seaweed-derived crude levulinic acid (SDCLA), containing formic acid, residual sugars and dissolved minerals additionally, was proposed as co-feed along with the biodiesel residues. Experiments were conducted at 100mL scale in batch process. Whereas the PHA yield was only 0.40 ± 0.01 g when only biodiesel residues were employed, it rose to 1.07 ± 0.02 g in presence of 0.35% (w/v) of SDCLA. The corresponding carbon utilisation efficiencies were 29.3% and 57.5%, respectively. 3-Hydroxy valerate incorporation in the PHA was pronounced in presence of SDCLA, with associated changes in polymer properties. The microbial synthesis fared poorly when SDCLA was substituted with pure levulinic acid. Thus, Halomonas hydrothermalis had a poor response to levulinic acid, as such, and other constituents present in SDCLA appear to have played a vital role in bacterial cell division and accumulation of PHA. Biodegradability tests in moist soil were also conducted as part of the study. Marine microalgal cultivation for biodiesel and seaweed cultivation for fuels may help generate biodiesel residues and crude levulinic acid in proximity, which would open up the possibility of large scale PHA manufacture in efficient and practical manner in the future through the methodology of the present study.

  5. Effects of Citric and Lactic Acid on the Reduction of Deoxynivalenol and Its Derivatives in Feeds

    PubMed Central

    Humer, Elke; Lucke, Annegret; Harder, Hauke; Metzler-Zebeli, Barbara U.; Böhm, Josef; Zebeli, Qendrim

    2016-01-01

    Exposure to mycotoxin-contaminated feeds represents a serious health risk. This has necessitated the need for the establishment of practical methods for mycotoxin decontamination. This study investigated the effects of citric acid (CA) and lactic acid (LA) on common trichothecene mycotoxins in feeds contaminated with Fusarium mycotoxins. Contaminated feed samples were processed either with 5% CA or 5% LA solutions in a ratio of 1:1.2 (w/v) for 5, 24, or 48 h, and analyzed for multiple mycotoxin metabolites using a liquid chromatography–tandem mass spectrometric method. The analyses showed that treating the feed with CA and LA lowered the concentration of deoxynivalenol (DON), whereby 5% LA lowered the original DON concentration in the contaminated feed samples by half, irrespective of the processing time. Similar lowering effects were observed for the concentrations of 15Ac-DON, 5-hydroxyculmorin, and sambucinol. The concentration of nivalenol was only lowered by the LA treatment. In contrast, CA and LA treatments showed no or only small effects on the concentration of several mycotoxins and their derivatives, including zearalenone, fumonisins, and culmorin. In conclusion, the present results indicate that the use of 5% solutions of LA and CA might reduce the concentration of common trichothecene mycotoxins, especially DON and its derivate 15Ac-DON. However, further research is required to determine the effect on overall toxicity and to identify the underlying mechanisms. PMID:27690101

  6. Mitochondrial DNA Fragmentation to Monitor Processing Parameters in High Acid, Plant-Derived Foods.

    PubMed

    Caldwell, Jane M; Pérez-Díaz, Ilenys M; Harris, Keith; Hassan, Hosni M; Simunovic, Josip; Sandeep, K P

    2015-12-01

    Mitochondrial DNA (mtDNA) fragmentation was assessed in acidified foods. Using quantitative polymerase chain reaction, Ct values measured from fresh, fermented, pasteurized, and stored cucumber mtDNA were determined to be significantly different (P > 0.05) based on processing and shelf-life. This indicated that the combination of lower temperature thermal processes (hot-fill at 75 °C for 15 min) and acidified conditions (pH = 3.8) was sufficient to cause mtDNA fragmentation. In studies modeling high acid juices, pasteurization (96 °C, 0 to 24 min) of tomato serum produced Ct values which had high correlation to time-temperature treatment. Primers producing longer amplicons (approximately 1 kb) targeting the same mitochondrial gene gave greater sensitivity in correlating time-temperature treatments to Ct values. Lab-scale pasteurization studies using Ct values derived from the longer amplicon differentiated between heat treatments of tomato serum (95 °C for <2 min). MtDNA fragmentation was shown to be a potential new tool to characterize low temperature (<100 °C) high acid processes (pH < 4.6), nonthermal processes such as vegetable fermentation and holding times of acidified, plant-derived products. PMID:26556214

  7. Modification of the cellulosic component of hemp fibers using sulfonic acid derivatives: Surface and thermal characterization.

    PubMed

    George, Michael; Mussone, Paolo G; Bressler, David C

    2015-12-10

    The aim of this study was to characterize the surface, morphological, and thermal properties of hemp fibers treated with two commercially available, inexpensive, and water soluble sulfonic acid derivatives. Specifically, the cellulosic component of the fibers were targeted, because cellulose is not easily removed during chemical treatment. These acids have the potential to selectively transform the surfaces of natural fibers for composite applications. The proposed method proceeds in the absence of conventional organic solvents and high reaction temperatures. Surface chemical composition and signature were measured using gravimetric analysis, X-ray photoelectron spectroscopy (XPS) and Fourier transform infra-red spectroscopy (FTIR). XPS data from the treated hemp fibers were characterized by measuring the reduction in O/C ratio and an increase in abundance of the C-C-O signature. FTIR confirmed the reaction with the emergence of peaks characteristic of disubstituted benzene and amino groups. Grafting of the sulfonic derivatives resulted in lower surface polarity. Thermogravimetric analysis revealed that treated fibers were characterized by lower percent degradation between 200 and 300 °C, and a higher initial degradation temperature.

  8. Synthesis and in vitro antitumor evaluation of dihydroartemisinin-cinnamic acid ester derivatives.

    PubMed

    Xu, Cang-Cang; Deng, Ting; Fan, Meng-Lin; Lv, Wen-Bo; Liu, Ji-Hua; Yu, Bo-Yang

    2016-01-01

    To explore novel high efficiency and low toxicity antitumor agents, a series of dihydroartemisinin-cinnamic acid ester derivatives modified on C-12 and/or C-9 position (s) were synthesized and the in vitro antitumor activities against PC-3, SGC-7901, A549 and MDA-MB-435s cancer cell lines were assessed. The hybrids (3-36) were prepared by esterification of 9α-hydroxyl-dihydroartemisinin (9α-OH DHA), the biotransformation product of dihydroartemisinin (DHA), and cinnamic acid derivatives. Compound 17 (IC50 = 0.20 μM) was the most potent anti-proliferative agent against the human lung carcinoma A549 cells, although it displayed low cytotoxicity on normal hepatic L-02 cells. The mechanism of action of compound 17 was further investigated by analysis of cell apoptosis and intracellular ROS generation. The results indicated that both ROS and ferrous ion contributed to the compound 17-induced cell death. Meanwhile, high intracellular ferrous ion and endogenous oxidative stress in A549 cells made them easier to suffer to compound 17-induced apoptosis. Our promising findings indicated the compound 17 could stand as drug candidate against lung cancer for further investigation.

  9. Alignment of Fatty Acid-Derived Triblock Copolymers under Large Amplitude Oscillatory Shear

    NASA Astrophysics Data System (ADS)

    Ding, Wenyue; Wang, Shu; Kesava, Sameer; Gomez, Enrique; Robertson, Megan

    Linear ABA triblock copolymers find widespread utilization as thermoplastic elastomers (TPEs): materials which exhibit elastomeric behavior at room temperature and can be readily processed at elevated temperatures. Traditional TPEs are derived from fossil fuels; however, the finite availability of petroleum and the environmental impact of petroleum processing has led to an increased interest in developing alternative sources for polymers. Vegetable oils and their fatty acids are promising replacements for petroleum sources due to their abundance, low cost, lack of toxicity, biodegradability and ease of functionalization that provides convenient routes to polymerization. In this study, triblock copolymer TPEs were synthesized containing lauryl and stearyl acrylate, derived from fatty acids found in vegetable oils. Small-angle X-ray scattering experiments revealed highly aligned triblock copolymer morphologies after the application of large amplitude oscillatory shear. The temperature and frequency dependence of the degree of alignment was investigated. In contrast to prior studies on shear-aligned morphologies in bulk and thin film block copolymers, hexagonal close packed and face centered cubic spherical structures were observed.

  10. Synthesis, spectroscopic characterizations, crystal structures and DFT studies of nalidixic acid carbonyl hydrazones derivatives

    NASA Astrophysics Data System (ADS)

    Bergamini, F. R. G.; Ribeiro, M. A.; Lancellotti, M.; Machado, D.; Miranda, P. C. M. L.; Cuin, A.; Formiga, A. L. B.; Corbi, P. P.

    2016-09-01

    This article describes the synthesis and characterization of the 1-ethyl-7-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carbohydrazide (hzd) and six carbonyl hydrazones derivatives of the nalidixic with 1H-pyrrol-2-ylmethylidene (hpyrr), 1H-imidazol-2-ylmethylidene (h2imi), pyridin-2-ylmethylidene (h2py), pyridin-3-ylmethylidene (h3py), pyridin-4-ylmethylidene(h4py) and (2-hydroxyphenyl)methylidene (hsali). The carbonyl hydrazones were characterized by elemental and ESI-QTOF-MS analyses, IR and detailed NMR spectroscopic measurements. The 2D NMR experiments allowed the unambiguous assignment of the hydrogen, carbon and nitrogen atoms, which have not been reported for nalidixic acid carbonyl hydrazone derivatives so far. Crystal structures of hzd and the new carbonyl hydrazones h2imi, hpyrr and h3py were determined by X-ray diffraction studies. Although the synthesis of hzd was reported decades ago, the hzd crystal structure have not been reported yet. Geometric optimizations of all the characterized structures were performed with the aid of DFT studies. Despite the fact that the hydrazones with 2-pyridine carboxylic acid (h2py) and salicyl aldehyde (hsali) were already reported by literature, a detailed spectroscopic study followed by DFT studies are also reported for such compounds in this manuscript. Antimicrobial studies of the compounds are also presented.

  11. Mitochondrial DNA Fragmentation to Monitor Processing Parameters in High Acid, Plant-Derived Foods.

    PubMed

    Caldwell, Jane M; Pérez-Díaz, Ilenys M; Harris, Keith; Hassan, Hosni M; Simunovic, Josip; Sandeep, K P

    2015-12-01

    Mitochondrial DNA (mtDNA) fragmentation was assessed in acidified foods. Using quantitative polymerase chain reaction, Ct values measured from fresh, fermented, pasteurized, and stored cucumber mtDNA were determined to be significantly different (P > 0.05) based on processing and shelf-life. This indicated that the combination of lower temperature thermal processes (hot-fill at 75 °C for 15 min) and acidified conditions (pH = 3.8) was sufficient to cause mtDNA fragmentation. In studies modeling high acid juices, pasteurization (96 °C, 0 to 24 min) of tomato serum produced Ct values which had high correlation to time-temperature treatment. Primers producing longer amplicons (approximately 1 kb) targeting the same mitochondrial gene gave greater sensitivity in correlating time-temperature treatments to Ct values. Lab-scale pasteurization studies using Ct values derived from the longer amplicon differentiated between heat treatments of tomato serum (95 °C for <2 min). MtDNA fragmentation was shown to be a potential new tool to characterize low temperature (<100 °C) high acid processes (pH < 4.6), nonthermal processes such as vegetable fermentation and holding times of acidified, plant-derived products.

  12. Dehydroabietic Acid Derivative QC2 Induces Oncosis in Hepatocellular Carcinoma Cells

    PubMed Central

    Zhang, Guang; Jiang, Chunping; Wang, Zhongxia; Chen, Weibo; Gu, Wen; Ding, Yitao

    2014-01-01

    Aim. Rosin, the traditional Chinese medicine, is reported to be able to inhibit skin cancer cell lines. In this report, we investigate the inhibitory effect against HCC cells of QC2, the derivative of rosin's main components dehydroabietic acid. Methods. MTT assay was used to determine the cytotoxicity of QC2. Morphological changes were observed by time-lapse microscopy and transmission electron microscopy and the cytoskeleton changes were observed by laser-scanning confocal microscopy. Cytomembrane integrity and organelles damage were confirmed by detection of the reactive oxygen (ROS), lactate dehydrogenase (LDH), and mitochondrial membrane potential (Δψm). The underlying mechanism was manifested by Western blotting. The oncotic cell death was further confirmed by detection of oncosis related protein calpain. Results. Swelling cell type and destroyed cytoskeleton were observed in QC2-treated HCC cells. Organelle damage was visualized by transmission electron microscopy. The detection of ROS accumulation, increased LDH release, and decreased ATP and Δψm confirmed the cell death. The oncotic related protein calpain was found to increase time-dependently in QC2-treated HCC cells, while its inhibitor PD150606 attenuated the cytotoxicity. Conclusions. Dehydroabietic acid derivative QC2 activated oncosis related protein calpain to induce the damage of cytomembrane and organelles which finally lead to oncosis in HCC cells. PMID:25110686

  13. Plant regeneration and biochemical accumulation of hydroxybenzoic and hydroxycinnamic acid derivatives in Hypoxis hemerocallidea organ and callus cultures.

    PubMed

    Moyo, Mack; Amoo, Stephen O; Aremu, Adeyemi O; Gruz, Jiří; Subrtová, Michaela; Doležal, Karel; Van Staden, Johannes

    2014-10-01

    Micropropagation of Hypoxis hemerocallidea Fisch. and C.A. Mey was used as a model system to study the influence of cytokinins (CKs) on plant regeneration and biochemical accumulation of hydroxybenzoic and hydroxycinnamic acid derivatives in organ and callus cultures and their antioxidant activity. Fourteen free phenolic acids were detected using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) while antioxidant activity was evaluated using oxygen radical absorbance capacity (ORAC) and 2,2-diphenyl-1-picryl hydrazyl (DPPH) radical scavenging activity. Cytokinins had a significant effect on the biochemical accumulation of hydroxybenzoic and hydroxycinnamic acid derivatives in H. hemerocallidea organ cultures. In particular, meta-topolin-treated organ cultures produced high concentrations of gallic, protocatechuic, gentisic, p-hydroxybenzoic, m-hydroxybenzoic, salicylic, chlorogenic and trans-cinnamic acids. The isoprenoid CK, N(6)-(2-isopentenyl)-adenine significantly increased the accumulation of hydroxycinnamic acid derivatives, namely, caffeic, p-coumaric, sinapic and ferulic acids. Cytokinin-treated organ cultures exhibited a significant increase in antioxidant activity, particularly in the ORAC model. In callus cultures, CKs decreased the concentrations of hydroxycinnamic acid derivatives and antioxidant activity when compared to the control. Overall, both CK type and concentration had a significant effect on plant regeneration, callus proliferation, biochemical accumulation of free phenolic acids and antioxidant activity of the resultant extracts.

  14. Indium metal-organic frameworks as high-performance heterogeneous catalysts for the synthesis of amino acid derivatives.

    PubMed

    Xia, Jing; Xu, Jianing; Fan, Yong; Song, Tianyou; Wang, Li; Zheng, Jifu

    2014-10-01

    Indium metal-organic frameworks (MOFs) were first used as recyclable heterogeneous Lewis acid catalysts for the synthesis of amino acid derivatives with excellent conversion yields. Moreover, exposed ether groups (Lewis basic sites) on the pore walls of In-MOF 2 could activate trimethylsilyl cyanide, forming hypervalent silicate intermediates, as proven by (29)Si NMR.

  15. Semisynthesis of Derivatives of Oleanolic Acid from Syzygium aromaticum and Their Antinociceptive and Anti-Inflammatory Properties.

    PubMed

    Rali, Sibusiso; Oyedeji, Opeoluwa O; Aremu, Olukayode O; Oyedeji, Adebola O; Nkeh-Chungag, Benedicta N

    2016-01-01

    Oleanolic acid is a pentacyclic triterpenoid compound widely found in plants and well known for its medicinal properties. Oleanolic acid (OA) was isolated from the ethyl acetate extract of Syzygium aromaticum flower buds. Semisynthesis afforded both acetate and ester derivatives. The derived compounds were monitored with thin layer chromatography and confirmed with nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry (MS), Fourier infrared (FT-IR) spectroscopy, and melting point (Mp). All these compounds were evaluated for their analgesic and anti-inflammatory properties at a dose of 40 mg/kg. Significant analgesic and anti-inflammatory effects were noted for all OA-derived compounds. In the formalin-induced pain test, the derivatives showed better analgesic effects compared to their precursor, whereas, in the tale flick test, oleanolic acid proved to be superior in analgesic effects compared to all its derivatives with the exception of the acetyl derivative. Acute inflammatory tests showed that acetyl derivatives possessed better anti-inflammatory activity compared to the other compounds. In conclusion, semisynthesis of oleanolic acid yielded several derivatives with improved solubility and enhanced analgesic and anti-inflammatory properties. PMID:27382191

  16. Semisynthesis of Derivatives of Oleanolic Acid from Syzygium aromaticum and Their Antinociceptive and Anti-Inflammatory Properties

    PubMed Central

    Rali, Sibusiso; Aremu, Olukayode O.; Oyedeji, Adebola O.; Nkeh-Chungag, Benedicta N.

    2016-01-01

    Oleanolic acid is a pentacyclic triterpenoid compound widely found in plants and well known for its medicinal properties. Oleanolic acid (OA) was isolated from the ethyl acetate extract of Syzygium aromaticum flower buds. Semisynthesis afforded both acetate and ester derivatives. The derived compounds were monitored with thin layer chromatography and confirmed with nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry (MS), Fourier infrared (FT-IR) spectroscopy, and melting point (Mp). All these compounds were evaluated for their analgesic and anti-inflammatory properties at a dose of 40 mg/kg. Significant analgesic and anti-inflammatory effects were noted for all OA-derived compounds. In the formalin-induced pain test, the derivatives showed better analgesic effects compared to their precursor, whereas, in the tale flick test, oleanolic acid proved to be superior in analgesic effects compared to all its derivatives with the exception of the acetyl derivative. Acute inflammatory tests showed that acetyl derivatives possessed better anti-inflammatory activity compared to the other compounds. In conclusion, semisynthesis of oleanolic acid yielded several derivatives with improved solubility and enhanced analgesic and anti-inflammatory properties. PMID:27382191

  17. Pyrimidinyl-arylpropionic acid derivatives: viable resources in the development of new antineoplastic agents.

    PubMed

    Xiong, Xishan; Wang, Li; Ye, Yangliang; Fu, Lili; Chen, Minli; Wang, Qingyi; Liu, Moyan; Tang, Jing; Dai, Bing; Shen, Jianhua; Mei, Changlin

    2010-08-01

    Numerous studies have documented that various naturally derived ligands or synthetic non-thiazolidinediones (TZD) as peroxisome proliferator-activated receptor gamma (PPARgamma) agonists have shown moderate or potent antitumor activities, which is PPARgamma independent or partially dependent. However, the PPARgamma agonistic or glucose-lowering activity is ranked first more often than antitumor activity to determine promising novel PPARgamma agonists for potential clinical use. In this study, we hypothesized that there might exist some compounds with less PPARgamma agonistic activity but potent antitumor activity. Thereafter, we evaluated the PPARgamma agonistic and antitumor activity of a novel series of alpha-aryloxy-alpha-methylhydrocinnamic acid derivatives synthesized with the initial aim of developing novel PPARgamma agonists as hypoglycemic agents. MTT assay results revealed that several compounds were able to inhibit cell proliferation in a dose-dependent manner with IC(50) 12.7-29.7 microM, better than that of rosiglitazone (45.9-141 microM), although the PPARgamma agonistic activity of most compounds is much lower than rosiglitazone. Some compounds induced cell cycle arrest and apoptosis tested by Flow Cytometry. Oral administration of DH9 (100 mg/kg/d) for 21 days to BALB/c nude mice bearing xenografts including MGC-803, NCI-H460, HT-29 and OS-RC-2 cells significantly retarded tumor growth. DG8 and DJ5 showed benefits in some of the above four xenografts. Our findings demonstrate that these compounds have potent antitumor activity in vitro and in vivo and pyrimidinyl-arylpropionic acid derivatives might be viable resources in the development of new antineoplastic agents.

  18. Synthesis of ω-Oxo Amino Acids and trans-5-Substituted Proline Derivatives Using Cross-Metathesis of Unsaturated Amino Acids.

    PubMed

    Salih, Nabaz; Adams, Harry; Jackson, Richard F W

    2016-09-16

    A range of 7-oxo, 8-oxo, and 9-oxo amino acids, analogues of 8-oxo-2-aminodecanoic acid, one of the key components of the cyclic tetrapeptide apicidin, have been prepared by a three-step process involving copper-catalyzed allylation of serine-, aspartic acid-, and glutamic acid-derived organozinc reagents, followed by cross-metathesis of the resulting terminal alkenes with unsaturated ketones and hydrogenation. The intermediate 7-oxo-5-enones underwent a highly diastereoselective (dr ≥96:4) acid-catalyzed aza-Michael reaction to give trans-2,5-disubstituted pyrrolidines, 5-substituted proline derivatives. The aza-Michael reaction was first observed when the starting enones were allowed to stand in solution in deuterochloroform but can be efficiently promoted by catalytic amounts of dry HCl. PMID:27529354

  19. Host-derived amino acids support the proliferation of symbiotic bacteria

    PubMed Central

    Graf, Joerg; Ruby, Edward G.

    1998-01-01

    Animals are typically colonized by diverse bacterial symbionts, many of which are commensal and, in numerous cases, even essential for their host’s proper development and growth. In exchange, the host must supply a sufficient array and quantity of nutrients to support the proliferation and persistence of its microbial community. In this investigation, we have examined such a nutritional environment by determining the symbiotic competence of auxotrophic mutants of the bioluminescent bacterium Vibrio fischeri, and have demonstrated that the host squid Euprymna scolopes provides at least 9 aa to the growing culture of symbiotic V. fischeri present in its light-emitting organ. We also collected and analyzed the extracellular fluid from this organ, in which the symbionts reside, and confirmed that it contained significant amounts of amino acids. The combined results suggested that host-derived free amino acids, as well as peptides or proteins, are a source of the amino acids that support the growth of the symbionts. This work describes a technique to sample the symbionts and their surrounding environment without contamination by host tissue components and, in combination with molecular genetic studies, allows the characterization of the nutritional conditions that support a cooperative animal–bacterial symbiosis. PMID:9465100

  20. Isolation of a new bioactive cinnamic acid derivative from the whole plant of Viola betonicifolia.

    PubMed

    Muhammad, Naveed; Saeed, Muhammad; Adhikari, Achyut; Khan, Khalid Muhammad; Khan, Haroon

    2013-10-01

    A new cinnamic acid derivative was isolated from the whole plant of Viola betonicifolia as off white needle. On the basis of various modern spectroscopic techniques including HREI-MS and 1D and 2D NMR, its structure was elucidated as 2,4-dihydroxy, 5-methoxy-cinnamic acid. It showed marked inhibition against DPPH (diphenyl-2-picryl hydrazyl) free radicals with IC50 = 124 ± 5.76 µM. The antioxidant property of the compound was compared with α-tocopherole and vitamin C having IC50 values 96 ± 0.46 and 90 ± 0.56 µM, respectively. In case of antiglycation assay, the compound exhibited moderate activity (IC50 = 355 ± 7.56 µM) similar to standard compound, rutin (IC50 = 294 ± 0.56 µM). However, it was non-toxic to PC-3 cell line. It is concluded that 2,4-dihydroxy, 5-methoxy-cinnamic acid has antiglycation potential which was further augmented by its antioxidant activity and thus offered an ideal natural therapeutic option for the effective management of diabetes.

  1. Synthesis and biological evaluation of enantiomerically pure glyceric acid derivatives as LpxC inhibitors.

    PubMed

    Tangherlini, Giovanni; Torregrossa, Tullio; Agoglitta, Oriana; Köhler, Jens; Melesina, Jelena; Sippl, Wolfgang; Holl, Ralph

    2016-03-01

    Inhibitors of the UDP-3-O-[(R)-3-hydroxymyristoyl]-N-acetylglucosamine deacetylase (LpxC) represent a promising class of novel antibiotics, selectively combating Gram-negative bacteria. In order to elucidate the impact of the hydroxymethyl groups of diol (S,S)-4 on the inhibitory activity against LpxC, glyceric acid ethers (R)-7a, (S)-7a, (R)-7b, and (S)-7b, lacking the hydroxymethyl group in benzylic position, were synthesized. The compounds were obtained in enantiomerically pure form by a chiral pool synthesis and a lipase-catalyzed enantioselective desymmetrization, respectively. The enantiomeric hydroxamic acids (R)-7b (Ki=230nM) and (S)-7b (Ki=390nM) show promising enzyme inhibition. However, their inhibitory activities do not substantially differ from each other leading to a low eudismic ratio. Generally, the synthesized glyceric acid derivatives 7 show antibacterial activities against two Escherichia coli strains exceeding the ones of their respective regioisomes 6.

  2. Luminescence behavior of terbium sulphosalicylic acid complexes in sol-gel derived host materials

    SciTech Connect

    Fan, X.; Wang, M.; Wang, Z.; Hong, Z.

    1997-08-01

    The formation and luminescence behavior of terbium sulphosalicylic acid (TbSSA) complexes in sol-gel derived host materials have been investigated. The 5-sulphosalicylic acid (H{sub 3}SSA) was dissolved in ethanol in advance, and then the TbCl{sub 3} and ethanol containing H{sub 3}SSA were introduced into the initial precursor sol, respectively. The resulting sol exhibits intramolecular energy transfer from the coordinated sulphosalicylic acid to the terbium ion. The TbSSA complex has formed in the TbCl{sub 3} and H{sub 3}SSA codoped sol. The complexes were found to have notably higher fluorescence intensities than TbCl{sub 3} in both the sol and the gel. In the sol, the concentration quenching was a diffusion-controlled process due to aggregation and effective collision between molecules and the fluorescence was decreased with increase of H{sub 3}SSA concentration. On the other hand, the molecules in the gel were isolated in the pores of the silica network. The fluorescence intensities of TbSSA in the gel were increased with the increase of concentration ratio of H{sub 3}SSA/TbCl{sub 3}. Maximum fluorescence intensity was obtained at H{sub 3}SSA/TbCl{sub 3} = 2.

  3. DFT computational study on decarboxylation mechanism of salicylic acid and its derivatives in the anionic state

    NASA Astrophysics Data System (ADS)

    Gao, Lu; Hu, Yanying; Zhang, Huitu; Liu, Yanchun; Song, Zhidan; Dai, Yujie

    2016-07-01

    The mechanisms of the decarboxylation of salicylic acid anion and its ortho substituted derivatives in gas phase and aqueous solution have been investigated by B3LYP method of DFT theory using the 6-31++G (d,p) basis set. The decarboxylation process includes hydrogen transfers from hydroxyl to carboxyl group and from carboxyl to the α-C of the aryl ring. The mechanism suggested is a pseudo-unimolecular decomposition of the salicylic acid anion and the hydrogen transfer from carboxyl to the α-C of the aryl ring is the rate determining step. Compared with the decarboxylation process in gas phase, the energy barriers in aqueous solution approximately declined by 25%-31%with the water mediation of the hydrogen transfer from carboxyl to the α-C of the aryl ring. The effects of substituents at the ortho position on the decarboxylation process were also investigated. Both the electron donating CH3 and withdrawing group NO2 at the ortho position of carboxyl group can further reduce the reaction energy barriers of the decarboxylation of salicylic acid anions.

  4. The effect of short-chain fatty acids on human monocyte-derived dendritic cells

    PubMed Central

    Nastasi, Claudia; Candela, Marco; Bonefeld, Charlotte Menné; Geisler, Carsten; Hansen, Morten; Krejsgaard, Thorbjørn; Biagi, Elena; Andersen, Mads Hald; Brigidi, Patrizia; Ødum, Niels; Litman, Thomas; Woetmann, Anders

    2015-01-01

    The gut microbiota is essential for human health and plays an important role in the pathogenesis of several diseases. Short-chain fatty acids (SCFA), such as acetate, butyrate and propionate, are end-products of microbial fermentation of macronutrients that distribute systemically via the blood. The aim of this study was to investigate the transcriptional response of immature and LPS-matured human monocyte-derived DC to SCFA. Our data revealed distinct effects exerted by each individual SCFA on gene expression in human monocyte-derived DC, especially in the mature ones. Acetate only exerted negligible effects, while both butyrate and propionate strongly modulated gene expression in both immature and mature human monocyte-derived DC. An Ingenuity pathway analysis based on the differentially expressed genes suggested that propionate and butyrate modulate leukocyte trafficking, as SCFA strongly reduced the release of several pro-inflammatory chemokines including CCL3, CCL4, CCL5, CXCL9, CXCL10, and CXCL11. Additionally, butyrate and propionate inhibited the expression of lipopolysaccharide (LPS)-induced cytokines such as IL-6 and IL-12p40 showing a strong anti-inflammatory effect. This work illustrates that bacterial metabolites far from the site of their production can differentially modulate the inflammatory response and generally provides new insights into host-microbiome interactions. PMID:26541096

  5. Structural Investigation for Optimization of Anthranilic Acid Derivatives as Partial FXR Agonists by in Silico Approaches

    PubMed Central

    Chen, Meimei; Yang, Xuemei; Lai, Xinmei; Kang, Jie; Gan, Huijuan; Gao, Yuxing

    2016-01-01

    In this paper, a three level in silico approach was applied to investigate some important structural and physicochemical aspects of a series of anthranilic acid derivatives (AAD) newly identified as potent partial farnesoid X receptor (FXR) agonists. Initially, both two and three-dimensional quantitative structure activity relationship (2D- and 3D-QSAR) studies were performed based on such AAD by a stepwise technology combined with multiple linear regression and comparative molecular field analysis. The obtained 2D-QSAR model gave a high predictive ability (R2train = 0.935, R2test = 0.902, Q2LOO = 0.899). It also uncovered that number of rotatable single bonds (b_rotN), relative negative partial charges (RPC−), oprea's lead-like (opr_leadlike), subdivided van der Waal’s surface area (SlogP_VSA2) and accessible surface area (ASA) were important features in defining activity. Additionally, the derived3D-QSAR model presented a higher predictive ability (R2train = 0.944, R2test = 0.892, Q2LOO = 0.802). Meanwhile, the derived contour maps from the 3D-QSAR model revealed the significant structural features (steric and electronic effects) required for improving FXR agonist activity. Finally, nine newly designed AAD with higher predicted EC50 values than the known template compound were docked into the FXR active site. The excellent molecular binding patterns of these molecules also suggested that they can be robust and potent partial FXR agonists in agreement with the QSAR results. Overall, these derived models may help to identify and design novel AAD with better FXR agonist activity. PMID:27070594

  6. Neutral and acidic products derived from hydroxyl radical-induced oxidation of arabinotriose assessed by electrospray ionisation mass spectrometry.

    PubMed

    Moreira, Ana S P; da Costa, Elisabete V; Evtuguin, Dmitry V; Coimbra, Manuel A; Nunes, Fernando M; Domingues, M Rosário M

    2014-04-01

    The oxidation of α-(1 → 5)-L-arabinotriose (Ara3), an oligosaccharide structurally related to side chains of coffee arabinogalactans, was studied in reaction with hydroxyl radicals generated under conditions of Fenton reaction (Fe(2+)/H2O2). The acidic and neutral oxidation products were separated by ligand exchange/size-exclusion chromatography, subsequently identified by electrospray ionisation mass spectrometry (ESI-MS) and structurally characterised by tandem MS (ESI-MS/MS). In acidic fraction were identified several oxidation products containing an acidic residue at the corresponding reducing end of Ara3, namely arabinonic acid, and erythronic, glyceric and glycolic acids formed by oxidative scission of the furanose ring. In neutral fractions were identified derivatives containing keto, hydroxy and hydroperoxy moieties, as well as derivatives resulting from the ring scission at the reducing end of Ara3. In both acidic and neutral fractions, beyond the trisaccharide derivatives, the corresponding di- and monosaccharide derivatives were identified indicating the occurrence of oxidative depolymerisation. The structural characterisation of these oxidation products by ESI-MS/MS allowed the differentiation of isobaric and isomeric species of acidic and neutral character. The species identified in this study may help in detection of roasting products associated with the free radical-mediated oxidation of coffee arabinogalactans.

  7. Comparing organic acids and salt derivatives as antimicrobials against selected poultry-borne Listeria monocytogenes strains in vitro.

    PubMed

    Lues, Jan Frederick Rykers; Theron, Maria Magdalena

    2012-12-01

    This article reports on the antilisterial properties of selected organic acids and salt derivatives in order to suggest possible alternatives in food preservation and pathogen control in the poultry meat processing industry. The susceptibility of two Listeria monocytogenes isolates was assessed against five organic acids (lactic, acetic, malic, citric, and propionic) and two acid-salt derivatives (sorbic acid [potassium salt] and benzoic acid [sodium salt]) across a series of pH environments. Minimum inhibitory concentrations (MICs) of the acids were tested against the two strains by means of an agar-dilution method. In general, strain CC60 was found to be more resistant than strain CC77 to both organic acids and salts. At pH values of 7 and above, high MIC levels (low susceptibility) were noted for potassium sorbate, sodium benzoate, and lactic acids, whereas susceptibility at lower pH increased reaching pH5 where the isolates were susceptible to all the organic acids tested. A small increase in pH notably reduced antimicrobial activity against the organisms. At pH 7, the isolates just about lost susceptibility to benzoic, lactic, malic, and sorbic acids. Although the activity of the majority of acids was linked to pH, some acids were not as closely related (e.g., potassium sorbate, sodium benzoate, and citric acid), and this suggests that the type of organic acids plays a role in inhibition. The relatively high MICs reported for compounds that are conventionally used as preservatives against Listeria spp. raise concern. The results furthermore suggest that the type of organic acid used to set pH, and not only pH alone, plays a role in determining inhibition. It was confirmed that a "one size fits all" approach to preservation is not always effective. Furthermore, the need for microbiological data to the subspecies level to inform the selection of preservatives was highlighted. PMID:23190165

  8. Interaction of cinnamic acid derivatives with commercial hypoglycemic drugs on 2-deoxyglucose uptake in 3T3-L1 adipocytes.

    PubMed

    Prabhakar, Pranav Kumar; Doble, Mukesh

    2011-09-28

    Hydroxycinnamic acid derivatives are naturally occurring substances found in fruits, vegetables, and flowers and are consumed as dietary phenolic compounds. The effect of cinnamic acid, ferulic acid, p-coumaric acid, eugenol, chlorogenic acid, and caffeic acid, alone and in combination with two commercial oral hypoglycemic drugs (OHD), namely, thiazolidinedione (THZ) and metformin, on the uptake of 2-deoxyglucose (2DG) by 3T3-L1 adipocytes is studied. All of the phytochemicals other than cinnamic acid show synergistic interaction in 2DG uptake with both of the OHDs. THZ (20 μM) in combination with ferulic acid (25 μM) or p-coumaric acid (25 μM) increases 2DG uptake by 7- or 6.34-fold, respectively, with respect to control, whereas metformin (20 μM), along with ferulic acid (25 μM) or cinnamic acid (25 μM), increases 2DG uptake by 6.45- or 5.87-fold, respectively, when compared to control. Chlorogenic and cinnamic acids increased the expression of PPARγ, whereas other hydroxycinnamic acids enhanced the expression of PI3K, indicating different mechanisms of action between these compounds. These phytochemicals were able to reduce the expressions of the fatty acid synthase and HMG CoA reductase genes, indicating that they may be able to reduce the secondary complications caused by the accumulation of lipids. These studies suggest that hydroxycinnamic acid derivatives may be beneficial for the treatment of diabetes mellitus. They may act as a supplement with commercial drugs and may reduce the secondary complications caused by OHDs.

  9. Gallic acid-based indanone derivative interacts synergistically with tetracycline by inhibiting efflux pump in multidrug resistant E. coli.

    PubMed

    Dwivedi, Gaurav Raj; Tiwari, Nimisha; Singh, Aastha; Kumar, Akhil; Roy, Sudeep; Negi, Arvind Singh; Pal, Anirban; Chanda, Debabrata; Sharma, Ashok; Darokar, Mahendra P

    2016-03-01

    The purpose of the present study was to study the synergy potential of gallic acid-based derivatives in combination with conventional antibiotics using multidrug resistant cultures of Escherichia coli. Gallic acid-based derivatives significantly reduced the MIC of tetracycline against multidrug resistant clinical isolate of E. coli. The best representative, 3-(3',4,'5'-trimethoxyphenyl)-4,5,6-trimethoxyindanone-1, an indanone derivative of gallic acid, was observed to inhibit ethidium bromide efflux and ATPase which was also supported by in silico docking. This derivative extended the post-antibiotic effect and decreased the mutation prevention concentration of tetracycline. This derivative in combination with TET was able to reduce the concentration of TNFα up to 18-fold in Swiss albino mice. This derivative was nontoxic and well tolerated up to 300 mg/kg dose in subacute oral toxicity study in mice. This is the first report of gallic acid-based indanone derivative as drug resistance reversal agent acting through ATP-dependent efflux pump inhibition.

  10. Radioiodinated Phenylalkyl Malonic Acid Derivatives as pH-Sensitive SPECT Tracers

    PubMed Central

    Bauwens, Matthias; De Saint-Hubert, Marijke; Cleynhens, Jan; Brams, Laura; Devos, Ellen; Mottaghy, Felix M.; Verbruggen, Alfons

    2012-01-01

    Introduction In vivo pH imaging has been a field of interest for molecular imaging for many years. This is especially important for determining tumor acidity, an important driving force of tumor invasion and metastasis formation, but also in the process of apoptosis. Methods 2-(4-[123I]iodophenethyl)-2-methylmalonic acid (IPMM), 2-(4-[123I]iodophenethyl)-malonic acid (IPM), 2-(4-[123I]iodobenzyl)-malonic acid (IBMM) and 4-[123I]iodophthalic acid (IP) were radiolabeled via the Cu+ isotopic nucleophilic exchange method. All tracers were tested in vitro in buffer systems to assess pH driven cell uptake. In vivo biodistribution of [123I]IPMM and [123I]IPM was determined in healthy mice and the pH targeting efficacy in vivo of [123I]IPM was evaluated in an anti-Fas monoclonal antibody (mAb) apoptosis model. In addition a mouse RIF-1 tumor model was explored in which tumor pH was decreased from 7.0 to 6.5 by means of induction of hyperglycemia in combination with administration of meta-iodobenzylguanidine. Results Radiosynthesis resulted in 15–20% for iodo-bromo exchange and 50–60% yield for iodo-iodo exchange while in vitro experiments showed a pH-sensitive uptake for all tracers. Shelf-life stability and in vivo stability was excellent for all tracers. [123I]IPMM and [123I]IPM showed a moderately fast predominantly biliary clearance while a high retention was observed in blood. The biodistribution profile of [123I]IPM was found to be most favorable in view of pH-specific imaging. [123I]IPM showed a clear pH-related uptake pattern in the RIF-1 tumor model. Conclusion Iodine-123 labeled malonic acid derivates such as [123I]IPM show a clearly pH dependent uptake in tumor cells both in vitro and in vivo which allows to visualize regional acidosis. However, these compounds are not suitable for detection of apoptosis due to a poor acidosis effect. PMID:22719886

  11. DFT and ab initio study of structure of dyes derived from 2-hydroxy and 2,4-dihydroxy benzoic acids

    NASA Astrophysics Data System (ADS)

    Dabbagh, Hossein A.; Teimouri, Abbas; Najafi Chermahini, Alireza; Shahraki, Maryam

    2008-02-01

    We present a detailed analysis of the structural, infrared spectra and visible spectra of a series of azo dyes preparation of salicylic acid and 2,4-dihydroxy benzoic acid derivatives as the coupling component. The preparation of these azo dyes with salicylic acid and 2,4-dihydroxy benzoic acid derivatives (salicylic acid, methyl salicylate, ethyl salicylate, butyl salicylate, methyl 2,4-dihydroxy benzoate, ethyl 2,4-dihydroxy benzoate, salicylaldehyde, salicylamide, 2,4-dihydroxy benzamide, salicylaldoxime) have been investigated theoretically by performing HF and DFT levels of theory using the standard 6-31G* basis set. The optimized geometries and calculated vibrational frequencies are evaluated via comparison with experimental values. The vibrational spectral data obtained from solid phase FT-IR spectra are assigned modes based on the results of the theoretical calculations. The observed spectra are found to be in good agreement with the calculations.

  12. Effect of processing and storage on the antioxidant ellagic acid derivatives and flavonoids of red raspberry (Rubus idaeus) jams.

    PubMed

    Zafrilla, P; Ferreres, F; Tomás-Barberán, F A

    2001-08-01

    From red raspberries, ellagic acid, its 4-arabinoside, its 4' (4' '-acetyl) arabinoside, and its 4' (4' '-acetyl)xyloside, as well as quercetin and kaempferol 3-glucosides, were identified. In addition, two unidentified ellagic acid derivatives were detected. The free radical scavenging activity of the ellagic acid derivatives was evaluated by using the DPPH method and compared to that of Trolox. All of the isolated compounds showed antioxidant activity. The effect of processing to obtain jams on raspberry phenolics was evaluated. The flavonol content decreased slightly with processing and more markedly during storage of the jams. The ellagic acid derivatives, with the exception of ellagic acid itself, remained quite stable with processing and during 6 months of jam storage. The content of free ellagic acid increased 3-fold during the storage period. The initial content (10 mg/kg of fresh weight of raspberries) increased 2-fold with processing, and it continued increasing up to 35 mg/kg after 1 month of storage of the jam. Then a slight decrease was observed until 6 months of storage had elapsed. The increase observed in ellagic acid could be explained by a release of ellagic acid from ellagitannins with the thermal treatment.

  13. Lewis Acid Pairs for the Activation of Biomass-derived Oxygenates in Aqueous Media

    SciTech Connect

    Roman, Yuriy

    2015-09-14

    The objective of this project is to understand the mechanistic aspects behind the cooperative activation of oxygenates by catalytic pairs in aqueous media. Specifically, we will investigate how the reactivity of a solid Lewis acid can be modulated by pairing the active site with other catalytic sites at the molecular level, with the ultimate goal of enhancing activation of targeted functional groups. Although unusual catalytic properties have been attributed to the cooperative effects promoted by such catalytic pairs, virtually no studies exist detailing the use heterogeneous water-tolerant Lewis pairs. A main goal of this work is to devise rational pathways for the synthesis of porous heterogeneous catalysts featuring isolated Lewis pairs that are active in the transformation of biomass-derived oxygenates in the presence of bulk water. Achieving this technical goal will require closely linking advanced synthesis techniques; detailed kinetic and mechanistic investigations; strict thermodynamic arguments; and comprehensive characterization studies of both materials and reaction intermediates. For the last performance period (2014-2015), two technical aims were pursued: 1) C-C coupling using Lewis acid and base pairs in Lewis acidic zeolites. Tin-, zirconium-, and hafnium containing zeolites (e.g., Sn-, Zr-, and Hf-Beta) are versatile solid Lewis acids that selectively activate carbonyl functional groups. In this aim, we demonstrate that these zeolites catalyze the cross-aldol condensation of aromatic aldehydes with acetone under mild reaction conditions with near quantitative yields. NMR studies with isotopically labeled molecules confirm that acid-base pairs in the Si-O-M framework ensemble promote soft enolization through α-proton abstraction. The Lewis acidic zeolites maintain activity in the presence of water and, unlike traditional base catalysts, in acidic solutions. 2) One-pot synthesis of MWW zeolite nanosheets for activation of bulky substrates. Through

  14. Synthesis, spectroscopic and conformational analysis of 1,4-dihydroisonicotinic acid derivatives

    NASA Astrophysics Data System (ADS)

    Goba, Inguna; Turovska, Baiba; Belyakov, Sergey; Liepinsh, Edvards

    2014-09-01

    Structural and conformational properties of 1,4-dihydroisonicotinic acid derivatives, characterized by ester, ketone or cyano functions at positions 3 and 5 in solid and liquid states have been investigated by X-ray analysis and nuclear magnetic resonance and supported by quantum chemical calculations. The dihydropyridine ring in each of the compounds exists in flattened boat-type conformation. The observed ring distortions around the C(4) and N(1) atoms are interrelated. The substituent at N(1) has great influence on nitrogen atom pyramidality. The 1H, 13C and 15N NMR chemical shifts and coupling constants are discussed in terms of their relationship to structural features such as character and position of the substituent in heterocycle, N-alkyl substitution and nitrogen lone pair delocalization within the conjugated system.

  15. Eicosanoids Derived From Arachidonic Acid and Their Family Prostaglandins and Cyclooxygenase in Psychiatric Disorders

    PubMed Central

    Yui, Kunio; Imataka, George; Nakamura, Hiroyuki; Ohara, Naoki; Naito, Yukiko

    2015-01-01

    Arachidonic acid (AA)-derived lipid mediators are called eicosanoids. Eicosanoids have emerged as key regulators of a wide variety of physiological responses and pathological processes, and control important cellular processes. AA can be converted into biologically active compounds by metabolism by cyclooxygenases (COX). Beneficial effect of COX-2 inhibitor celecoxib add-on therapy has been reported in early stage of schizophrenia. Moreover, add-on treatment of celecoxib attenuated refractory depression and bipolar depression. Further, the COX/prostaglandin E pathway play an important role in synaptic plasticity and may be included in pathophysiology in autism spectrum disorders (ASD). In this regard, plasma transferrin, which is an iron mediator related to eicosanoid signaling, may be related to social impairment of ASD. COX-2 is typically induced by inflammatory stimuli in the majority of tissues, and the only isoform responsible for propagating the inflammatory response. Thus, COX-2 inhibitors considered as the best target for Alzheimer’s disease. PMID:26521945

  16. Oxidation of cinnamic acid derivatives: A pulse radiolysis and theoretical study

    NASA Astrophysics Data System (ADS)

    Yadav, Pooja; Mohan, Hari; Maity, Dilip Kumar; Suresh, Cherumuttathu H.; Rao, B. S. Madhav

    2008-07-01

    Second order rate constants in the range of ( k = 1.6-4.5) × 10 9 dm 3 mol -1 s -1 were obtained for the rad OH induced oxidation of nitro- and methoxycinnamic acid derivatives in neutral solutions using pulse radiolysis. The transient absorption spectra exhibited a broad peak around 360-410 nm in o-methoxy, o- and p-nitrocinnamates or two peaks around 310-330 and 370-410 nm in other isomers. Quantum chemical calculations revealed that addition of rad OH to olefinic moiety yielded considerably more stable structures than ring addition products and the para system among the latter is the most stable. Spin density analysis suggested that olefinic adducts retained the aromaticity in contrast to its loss in ring rad OH adducts. An excellent linear correlation between the relative stabilities of the rad OH adducts (after accounting for the aromatic stabilization in olefinic adducts) and the maximum Sd values is also obtained.

  17. Hydroxamic acid derivatives: a promising scaffold for rational compound optimization in Chagas disease.

    PubMed

    de Menezes, Dayanne da Rocha; Calvet, Claudia Magalhães; Rodrigues, Giseli Capaci; de Souza Pereira, Mirian Claudia; Almeida, Igor Rodrigues; de Aguiar, Alcino Palermo; Supuran, Claudiu T; Vermelho, Alane Beatriz

    2016-12-01

    This work describes the antitrypanocidal activity of two hydroxamic acid derivatives containing o-ethoxy (HAD1) and p-ethoxy (HAD2) as substituent in the aromatic ring linked to the isoxazoline ring. HAD1 and HAD2 induced a significant reduction in the number of intracellular parasites and consequently showed activity on the multiplication of the parasite. Treatment of cardiomyocytes and macrophages with the compounds revealed no significant loss in cell viability. Ultrastructural alterations after treatment of cardiomyocytes or macrophages infected by Trypanosoma cruzi with the IC50 value of HAD1 revealed alterations to amastigotes, showing initial damage seen as swelling of the kinetoplast. This gave a good indication of the ability of the drug to permeate through the host cell membrane as well as its selectivity to the parasite target. Both compounds HAD1 and 2 were able to reduce the cysteine peptidases and decrease the activity of metallopeptidases.

  18. Synthesis of some novel D-glucuronic acid acetylated derivatives as potential anti-tumor agents.

    PubMed

    El-Nezhawy, Ahmed O H; Adly, Frady G; Eweas, Ahmed F; Hanna, Atef G; El-Kholy, Yehya M; El-Sayed, Shahenaz H; El-Naggar, Tarek B A

    2011-10-01

    A structurally diverse series of Δ(4,5) -uronamide derivatives have been chemically synthesized starting from D-glucuronic acid itself by means of acetylation, activation, amide bond formation and base-catalyzed elimination protocols. Structure elucidation for all products along with optimization of the synthetic steps is described. The synthesized compounds were evaluated for their in-vitro anti-tumor activity against MCF-7, TK-10 and UACC-62 cell lines. The compounds 5, 11, 13, 15 and 16 were the most active against TK-10 cell line. On the other hand, the most active compounds against the MCF-7 cell line were 11 and 15. However, compounds 5, 7, 11, 13, 15 and 16 were the most active against the UACC-62 cell line.

  19. Nitrooxyacyl derivatives of salicylic acid: aspirin-like molecules that covalently inactivate cyclooxygenase-1.

    PubMed

    Cena, Clara; Tosco, Paolo; Marini, Elisabetta; Lazzarato, Loretta; Piccinini, Marco; Ramondetti, Cristina; Lupino, Elisa; Fruttero, Roberta; Gasco, Alberto

    2011-03-01

    A recently described series of nitrooxyacyl derivatives of salicylic acid, displaying aspirin-like anti-inflammatory and platelet anti-aggregatory properties, were evaluated for their abilities to inhibit cyclooxygenase (COX). A number of these compounds irreversibly inhibited both COX-1 and COX-2 isoforms when tested in isolated human platelets and monocytes. Further studies using COX-1 expressed in human HEK293T cells showed that this inhibition mechanism is similar to that of aspirin; namely, the products are able to covalently bind to the Ser 530 residue present in the active cleft of the enzyme. Molecular modeling enabled us to rationalize this behavior. Because these products were previously found to display NO-dependent properties in rat animal models, particularly as they decreased in vivo gastrotoxicity and induced in vitro vasodilation, they represent a new and interesting class of potential aspirin-like antithrombotic agents worthy of further study.

  20. Acidic resin-catalysed conversion of fructose into furan derivatives in low boiling point solvents.

    PubMed

    Zhu, Hong; Cao, Quan; Li, Chunhu; Mu, Xindong

    2011-09-27

    Conversion of fructose into furan derivatives 5-hydroxymethylfurfural (HMF) and 5-methoxymethylfurfural (MMF) is performed in tetrahydrofuran (THF) and methanol-organic solvent systems, catalysed by an acidic resin Amberlyst-15. The melted fructose can be converted into HMF on the surface of the solid resin catalyst in the presence of THF as an extracting phase, which is a good solvent for HMF and other by-products. The solid resin catalyst can be reused eleven times without losing its catalytic ability, with an average HMF yield of approximately 50%. Upon the addition of methanol, the generated HMF can further react with methanol to form MMF, and the total yield of HMF and MMF could be promoted to 65%. GC-MS analysis confirms the formation of a small amount of methyl levulinate in methanolorganic solvent system.

  1. Fluorinated betulinic acid derivatives and evaluation of their anti-HIV activity.

    PubMed

    Li, Jizhen; Goto, Masuo; Yang, Xiaoming; Morris-Natschke, Susan L; Huang, Li; Chen, Chin-Ho; Lee, Kuo-Hsiung

    2016-01-01

    Several fluorinated derivatives of the anti-HIV maturation agent bevirimat (1) were synthesized and evaluated for anti-HIV replication activity. The modified positions were the C-2, C-3, C-28, and C-30 positions, either directly on the betulinic acid (2) skeleton or in the attached side chains. Compound 18, which has a trifluoromethyl group added to C-30 of its isopropenyl group, exhibited similar potency to 1 against HIV-1NL4-3. In total, our current studies support our prior conclusion that C-30 allylic modification is unlikely to be a pharmacophore for anti-HIV activity, but could be a meaningful route to manipulate other properties of 2-related compounds.

  2. Bioactive Compounds Derived from the Yeast Metabolism of Aromatic Amino Acids during Alcoholic Fermentation

    PubMed Central

    Guillamon, Jose Manuel; Torija, Maria Jesus; Beltran, Gemma; Troncoso, Ana M.; Garcia-Parrilla, M. Carmen

    2014-01-01

    Metabolites resulting from nitrogen metabolism in yeast are currently found in some fermented beverages such as wine and beer. Their study has recently attracted the attention of researchers. Some metabolites derived from aromatic amino acids are bioactive compounds that can behave as hormones or even mimic their role in humans and may also act as regulators in yeast. Although the metabolic pathways for their formation are well known, the physiological significance is still far from being understood. The understanding of this relevance will be a key element in managing the production of these compounds under controlled conditions, to offer fermented food with specific enrichment in these compounds or even to use the yeast as nutritional complements. PMID:24895623

  3. Hydroxycinnamic acid-derived polymers constitute the polyaromatic domain of suberin

    NASA Technical Reports Server (NTRS)

    Bernards, M. A.; Lopez, M. L.; Zajicek, J.; Lewis, N. G.

    1995-01-01

    Suberin is an abundant, complex, intractable, plant cell wall polymeric network that forms both protective and wound-healing layers. Its function is, therefore, critical to the survival of all vascular plants. Its chemical structure and biosynthesis are poorly defined, although it is known to consist of both aromatic and aliphatic domains. While the composition of the aliphatic component has been fairly well characterized, that of the phenolic component has not. Using a combination of specific carbon-13 labeling techniques, and in situ solid state 13C NMR spectroscopic analysis, we now provide the first direct evidence for the nature of the phenolic domain of suberin and report here that it is almost exclusively comprised of a covalently linked, hydroxycinnamic acid-derived polymeric matrix.

  4. Corrosion Inhibition of Carbon Steel by New Thiophene Azo Dye Derivatives in Acidic Solution

    NASA Astrophysics Data System (ADS)

    El-Haddad, Mahmoud N.; Fouda, A. S.; Mostafa, H. A.

    2013-08-01

    Inhibition of carbon steel corrosion in 2 M hydrochloric acid (HCl) solution by thiophene azo dye derivatives were studied using weight loss, electrochemical frequency modulation (EFM), and atomic absorption techniques. The experimental data suggest that the inhibition efficiency increases with increasing inhibitors concentration in presence of 103 μM potassium iodide (KI). This is due to synergistic effect. Thus, the experimental results suggested that the presence of these anions in the solution stabilized the adsorption of inhibitors molecules on the metal surface and improved the inhibition efficiency. The results of EFM experiments are a spectrum of current response as a function of frequency. The corrosion rate and Tafel parameters can be obtained with measurement by analyzing the harmonic frequencies. The adsorption of the inhibitors on metal surface obeys the Langmuir adsorption isotherm. The surface of metal examined using Fourier transform infrared and ultraviolet spectroscopy. Quantum chemical calculations were carried out and relations between computed parameters and experimental inhibition efficiency were discussed.

  5. Arachidonic acid-derived signaling lipids and functions in impaired healing

    PubMed Central

    Dhall, Sandeep; Wijesinghe, Dayanjan Shanaka; Karim, Zubair A.; Castro, Anthony; Vemana, Hari Priya; Khasawneh, Fadi T.; Chalfant, Charles E.; Martins-Green, Manuela

    2016-01-01

    Very little is known about lipid function during wound healing, and much less during impaired healing. Such understanding will help identify what roles lipid signaling plays in the development of impaired/chronic wounds. We took a lipidomics approach to study the alterations in lipid profile in the LIGHT−/− mouse model of impaired healing which has characteristics that resemble those of impaired/chronic wounds in humans, including high levels of oxidative stress, excess inflammation, increased extracellular matrix degradation and blood vessels with fibrin cuffs. The latter suggests excess coagulation and potentially increased platelet aggregation. We show here that in these impaired wounds there is an imbalance in the arachidonic acid (AA) derived eicosonoids that mediate or modulate inflammatory reactions and platelet aggregation. In the LIGHT−/− impaired wounds there is a significant increase in enzymatically derived breakdown products of AA. We found that early after injury there was a significant increase in the eicosanoids 11-, 12-, and 15-hydroxyeicosa-tetranoic acid, and the proinflammatory leukotrienes (LTD4 and LTE) and prostaglandins (PGE2 and PGF2α). Some of these eicosanoids also promote platelet aggregation. This led us to examine the levels of other eicosanoids known to be involved in the latter process. We found that thromboxane (TXA2/B2), and prostacyclins 6kPGF1α are elevated shortly after wounding and in some cases during healing. To determine whether they have an impact in platelet aggregation and hemostasis, we tested LIGHT−/− mouse wounds for these two parameters and found that, indeed, platelet aggregation and hemostasis are enhanced in these mice when compared with the control C57BL/6 mice. Understanding lipid signaling in impaired wounds can potentially lead to development of new therapeutics or in using existing nonsteroidal anti-inflammatory agents to help correct the course of healing. PMID:26135854

  6. Synthesis and characterization of polymeric materials derived from 2,5-diketopiperazines and pyroglutamic acid

    NASA Astrophysics Data System (ADS)

    Parrish, Dennis Arch

    The research presented in this dissertation describes the investigation of 2,5-diketopiperazines (DKPs) as property modifiers for addition polymers and the self association behavior of pyroglutamic acid derivatives. The first project involved the copolymerization of methyl methacrylate and styrene with DKP-based methacrylate monomers. Low incorporations of serine- and aspartame-based DKPs in the copolymer resulted in dramatic increases in the glass transition temperature (Ts). The research presented in Chapter II focuses on the ring-opening reactions of pyroglutamic diketopiperazine (pyDKP). The original intent was to synthesize polymers containing backbone DKPs through ring-opening polymerization of the five-membered rings. However, it was discovered that regioselective ring-opening occurs at the six-membered ring to give pyroglutamic acid derivatives. Since this reaction had not been reported previously, the focus of research was altered to investigate the scope and limitations of the new reaction. The ring-opening reactions of pyDKP with diamines to give bispyroglutamides is described in Chapter IV. While these materials are not polymeric, they display polymeric behavior. It was found that multi-functional pyroglutamides display Tgs during thermal analysis, exhibit high thermal stability, and form melt-drawn fibers. In contrast, the materials have low solution viscosities and are freely soluble in water, ethanol, and chloroform. This behavior is attributed to non-covalent supramolecular associations. The final part of this dissertation involved the investigation of thermoreversible organic solvent gelators. The ring-opening reaction of pyDKP with long alkyl amines unexpectedly gelled the reaction solvent. A series of analogous gelators were synthesized, and the minimum concentration required for gelation in various solvents was determined. It was found that the nature of the solvent, alkyl chain length, and optical activity of the gelator determined gelator

  7. Direct hydrogenation of biomass-derived butyric acid to n-butanol over a ruthenium-tin bimetallic catalyst.

    PubMed

    Lee, Jong-Min; Upare, Pravin P; Chang, Jong-San; Hwang, Young Kyu; Lee, Jeong Ho; Hwang, Dong Won; Hong, Do-Young; Lee, Seung Hwan; Jeong, Myung-Geun; Kim, Young Dok; Kwon, Young-Uk

    2014-11-01

    Catalytic hydrogenation of organic carboxylic acids and their esters, for example, cellulosic ethanol from fermentation of acetic acid and hydrogenation of ethyl acetate is a promising possibility for future biorefinery concepts. A hybrid conversion process based on selective hydrogenation of butyric acid combined with fermentation of glucose has been developed for producing biobutanol. ZnO-supported Ru-Sn bimetallic catalysts exhibits unprecedentedly superior performance in the vapor-phase hydrogenation of biomass-derived butyric acid to n-butanol (>98% yield) for 3500 h without deactivation. PMID:25123894

  8. Direct hydrogenation of biomass-derived butyric acid to n-butanol over a ruthenium-tin bimetallic catalyst.

    PubMed

    Lee, Jong-Min; Upare, Pravin P; Chang, Jong-San; Hwang, Young Kyu; Lee, Jeong Ho; Hwang, Dong Won; Hong, Do-Young; Lee, Seung Hwan; Jeong, Myung-Geun; Kim, Young Dok; Kwon, Young-Uk

    2014-11-01

    Catalytic hydrogenation of organic carboxylic acids and their esters, for example, cellulosic ethanol from fermentation of acetic acid and hydrogenation of ethyl acetate is a promising possibility for future biorefinery concepts. A hybrid conversion process based on selective hydrogenation of butyric acid combined with fermentation of glucose has been developed for producing biobutanol. ZnO-supported Ru-Sn bimetallic catalysts exhibits unprecedentedly superior performance in the vapor-phase hydrogenation of biomass-derived butyric acid to n-butanol (>98% yield) for 3500 h without deactivation.

  9. Catalytic activity of the two-component flavin-dependent monooxygenase from Pseudomonas aeruginosa toward cinnamic acid derivatives.

    PubMed

    Furuya, Toshiki; Kino, Kuniki

    2014-02-01

    4-Hydroxyphenylacetate 3-hydroxylases (HPAHs) of the two-component flavin-dependent monooxygenase family are attractive enzymes that possess the catalytic potential to synthesize valuable ortho-diphenol compounds from simple monophenol compounds. In this study, we investigated the catalytic activity of HPAH from Pseudomonas aeruginosa strain PAO1 toward cinnamic acid derivatives. We prepared Escherichia coli cells expressing the hpaB gene encoding the monooxygenase component and the hpaC gene encoding the oxidoreductase component. E. coli cells expressing HpaBC exhibited no or very low oxidation activity toward cinnamic acid, o-coumaric acid, and m-coumaric acid, whereas they rapidly oxidized p-coumaric acid to caffeic acid. Interestingly, after p-coumaric acid was almost completely consumed, the resulting caffeic acid was further oxidized to 3,4,5-trihydroxycinnamic acid. In addition, HpaBC exhibited oxidation activity toward 3-(4-hydroxyphenyl)propanoic acid, ferulic acid, and coniferaldehyde to produce the corresponding ortho-diphenols. We also investigated a flask-scale production of caffeic acid from p-coumaric acid as the model reaction for HpaBC-catalyzed syntheses of hydroxycinnamic acids. Since the initial concentrations of the substrate p-coumaric acid higher than 40 mM markedly inhibited its HpaBC-catalyzed oxidation, the reaction was carried out by repeatedly adding 20 mM of this substrate to the reaction mixture. Furthermore, by using the HpaBC whole-cell catalyst in the presence of glycerol, our experimental setup achieved the high-yield production of caffeic acid, i.e., 56.6 mM (10.2 g/L) within 24 h. These catalytic activities of HpaBC will provide an easy and environment-friendly synthetic approach to hydroxycinnamic acids.

  10. Biodistribution profiling of the chemical modified hyaluronic acid derivatives used for oral delivery system.

    PubMed

    Hsieh, Chien-Ming; Huang, Yu-Wen; Sheu, Ming-Thau; Ho, Hsiu-O

    2014-03-01

    A series of adipic acid dihydrazide (ADH)-modified hyaluronic acid (HA-ADH) compounds were synthesized and conjugated with QDots (QDots-HA conjugates) to assess the effects of the molecular weight (MW) and extent of chemical modification of HA on its biodistribution. Their physicochemical structures were confirmed by complementary application of GPC, (1)H NMR, FTIR, and UV-vis spectroscopic methods. In vivo imaging of QDots-HA conjugates after oral administration was analyzed to investigate their biodistribution in nude mice. Simultaneously, real-time bioimaging was confirmed by an anatomical analysis to investigate the organ-specific accumulation of conjugates. QDot-HA conjugates with a higher MW of HA or high modification presented relatively slow clearance leading to an extension of the retention time for up to 10 days, whereas those with lower MWs of HA or a low modification extent exhibited quick absorption and elimination after oral administration. Taken together, HA derivatives with suitable MWs and chemical modification extents can be used to design new, more-sophisticated, and intelligent HA-based vehicles for oral delivery with diverse characteristics. PMID:24315950

  11. Usnic Acid Derivatives with Cytotoxic and Antifungal Activities from the Lichen Usnea longissima.

    PubMed

    Yu, Xuelong; Guo, Qiang; Su, Guozhu; Yang, Ailin; Hu, Zhongdong; Qu, Changhai; Wan, Zhe; Li, Ruoyu; Tu, Pengfei; Chai, Xingyun

    2016-05-27

    Eight usnic acid derivatives, that is, usenamines A-F (1-6), usone (7), and isousone (8), together with the known (+)-usnic acid (9), were isolated from the lichen Usnea longissima. Their structures were elucidated using 1D and 2D NMR and MS data, and the absolute configurations of compounds 1 and 2 were defined by single-crystal X-ray diffraction analyses. Compounds 1, 2, and 8 showed inhibitory effects on the growth of human hepatoma HepG2 cells with IC50 values of 6.0-53.3 μM compared with methotrexate as the positive control, which had an IC50 value of 15.8 μM. Furthermore, 1 induced apoptosis of HepG2 cells in a dose-dependent manner at concentrations of 0-15.0 μM. The isolated compounds were also evaluated for their antifungal and antibacterial activities, with 7 and 8 exhibiting weak inhibitory effects on fungal Trichophyton rubrum spp. with an MIC value of 41.0 μM. PMID:27186821

  12. Photochemistry and proton transfer reaction chemistry of selected cinnamic acid derivatives in hydrogen bonded environments

    NASA Astrophysics Data System (ADS)

    Huang, Yong; Russell, David H.

    1998-05-01

    Proton transfer reactions between cinnamic acid derivatives (MH) and ammonia are studied using a time-of-flight mass spectrometer equipped with a supersonic nozzle to entrain neutral species formed by 337 nm laser desorption. The supersonic nozzle is used to form clusters of the type MH(NH3)n where n ranges to numbers greater than 20. Multimeric clusters of MH, e.g. MH2(NH3)n are not detected in this experiment or are of low abundance. Photoexcitation of MH(NH3)n clusters by using 355 nm photons yields ionic species that correspond to direct multiphoton ionization, e.g. MH+[middle dot](NH3)n, and proton transfer reactions, e.g. H+(NH3)n. Analogous product ions are formed by photoexcitation of the methylamine, MH(CH3NH2)n, and ammonia/methanol, MH(NH3)(CH3OH)n, clusters. Detailed analysis of energetics data suggests that proton transfer occurs through neutral excited stare species, and a mechanism analogous to one proposed previously is used to rationalize the data. The energetics of proton transfer via a radical cation form of the cinnarnic acid dimer is also consistent with the data. The relevance of this work to fundamental studies of matrix-assisted laser desorption ionization (MALDI) is discussed. In particular, the role of excited state proton transfer (ESPT) in MALDI is discussed.

  13. Identification of KMU-3, a novel derivative of gallic acid, as an inhibitor of adipogenesis.

    PubMed

    Park, Yu-Kyoung; Lee, Jinho; Hong, Victor Sukbong; Choi, Jong-Soon; Lee, Tae-Yoon; Jang, Byeong-Churl

    2014-01-01

    Differentiation of preadipocyte, also called adipogenesis, leads to the phenotype of mature adipocyte. Excessive adipogenesis, however, is largely linked to the development of obesity. Herein we investigated a library of 53 novel chemicals, generated from a number of polyphenolic natural compounds, on adipogenesis. Strikingly, among the chemicals tested, KMU-3, a derivative of gallic acid, strongly suppressed lipid accumulation during the differentiation of 3T3-L1 preadipocytes into adipocytes. On mechanistic levels, KMU-3 inhibited expressions of CCAAT/enhancer-binding protein-α (C/EBP-α), peroxisome proliferator-activated receptor-γ (PPAR-γ), and fatty acid synthase (FAS) during adipocyte differentiation. Moreover, KMU-3 reduced expressions of adipokines, including retinol binding protein-4 (RBP-4), leptin, and regulated on activation, normal T cell expressed and secreted (RANTES) during adipocyte differentiation. Of further note, KMU-3 rapidly blocked the phosphorylation of signal transducer and activator of transcription-3 (STAT-3) during the early stage of adipogenesis. Importantly, pharmacological inhibition studies revealed that AG490, a JAK-2/STAT-3 inhibitor suppressed adipogenesis and STAT-3 phosphorylation, implying that early blockage of STAT-3 activity is crucial for the KMU-3-mediated anti-adipogenesis. These findings demonstrate firstly that KMU-3 inhibits adipogenesis by down-regulating STAT-3, PPAR-γ, C/EBP-α, and FAS. This work shows that KMU-3 is an inhibitor of adipogenesis and thus may have therapeutic potential against obesity.

  14. Derivatives of Salicylic Acid as Inhibitors of YopH in Yersinia pestis

    PubMed Central

    Huang, Zunnan; He, Yantao; Zhang, Xian; Gunawan, Andrea; Wu, Li; Zhang, Zhong-Yin; Wong, Chung F.

    2010-01-01

    Yersinia pestis causes diseases ranging from gastrointestinal syndromes to bubonic plague and could be misused as a biological weapon. As its protein tyrosine phosphatase YopH has already been demonstrated as a potential drug target, we have developed two series of forty salicylic acid derivatives and found sixteen to have micromolar inhibitory activity. We designed these ligands to have two chemical moieties connected by a flexible hydrocarbon linker to target two pockets in the active site of the protein to achieve binding affinity and selectivity. One moiety possessed the salicylic acid core intending to target the phosphotyrosine-binding pocket. The other moiety contained different chemical fragments meant to target a nearby secondary pocket. The two series of compounds differed by having hydrocarbon linkers with different lengths. Before experimental co-crystal structures are available, we have performed molecular docking to predict how these compounds might bind to the protein and to generate structural models for performing binding affinity calculation to aid future optimization of these series of compounds. PMID:20560978

  15. Synthesis, structural characterization and quantum chemical studies of silicon-containing benzoic acid derivatives

    NASA Astrophysics Data System (ADS)

    Zaltariov, Mirela-Fernanda; Cojocaru, Corneliu; Shova, Sergiu; Sacarescu, Liviu; Cazacu, Maria

    2016-09-01

    The present paper is concerned with the synthesis and molecular structure investigation of two new benzoic acid derivatives having trimethylsilyl tails, 4-((trimethylsilyl)methoxy) and 4-(3-(trimethylsilyl)propoxy)benzoic acids. The structures of the novel compounds have been confirmed by X-ray crystallography, Fourier-transform infrared spectroscopy (FTIR) and nuclear magnetic resonance (1H and 13C NMR). The theoretical studies of molecules were conducted by using the quantum chemical methods, such as Density Functional Theory (DFT B3LYP/6-31 + G**), Hartree-Fock (HF/6-31 + G**) and semiempirical computations (PM3, PM6 and PM7). The optimized molecular geometries have been found to be in good agreement with experimental structures resulted from the X-ray diffraction. The maximum electronic absorption bands observed at 272-287 nm (UV-vis spectra) have been assigned to π → π* transitions, which were in reasonable agreement with the time dependent density functional theory (TD-DFT) calculations. The computed vibrational frequencies by DFT method were assigned and compared with the experimental FTIR spectra. The mapped electrostatic potentials revealed the reactive sites, which corroborated the observation of the dimer supramolecular structures formed in the crystals by hydrogen-bonding. The energies of frontier molecular orbitals (HOMO and LUMO), energy gap, dipole moment and molecular descriptors for the new compounds were calculated and discussed.

  16. Synthesis and description of intermolecular interactions in new sulfonamide derivatives of tranexamic acid

    NASA Astrophysics Data System (ADS)

    Ashfaq, Muhammad; Arshad, Muhammad Nadeem; Danish, Muhammad; Asiri, Abdullah M.; Khatoon, Sadia; Mustafa, Ghulam; Zolotarev, Pavel N.; Butt, Rabia Ayub; Şahin, Onur

    2016-01-01

    Tranexamic acid (4-aminomethyl-cyclohexanecarboxylic acid) was reacted with sulfonyl chlorides to produce structurally related four sulfonamide derivatives using simple and environmental friendly method to check out their three-dimensional behavior and van der Walls interactions. The molecules were crystallized in different possibilities, as it is/after alkylation at its O and N atoms/along with a co-molecule. All molecules were crystallized in monoclinic crystal system with space group P21/n, P21/c and P21/a. X-ray studies reveal that the molecules stabilized themselves by different kinds of hydrogen bonding interactions. The molecules are getting connected through O-H⋯O hydrogen bonds to form inversion dimers which are further connected through N-H⋯O interactions. The molecules in which N and O atoms were alkylated showed non-classical interaction and generated centro-symmetric R22(24) ring motif. The co-crystallized host and guest molecules are connected to each other via O-H⋯O interactions to generate different ring motifs. By means of the ToposPro software an analysis of the topologies of underlying nets that correspond to molecular packings and hydrogen-bonded networks in structures under consideration was carried out.

  17. Potential gastroprotective effect of novel cyperenoic acid/quinone derivatives in human cell cultures.

    PubMed

    Theoduloz, Cristina; Carrión, Ivanna Bravo; Pertino, Mariano Walter; Valenzuela, Daniela; Schmeda-Hirschmann, Guillermo

    2012-11-01

    The stem bark of Tabebuia species and the rhizomes of Jatropha isabelii are used in Paraguayan traditional medicine to treat gastric lesions and as anti-inflammatory agents. The sesquiterpene cyperenoic acid obtained from J. isabelii has been shown to display a gastroprotective effect in animal models of induced gastric ulcers while the quinone lapachol shows several biological effects associated with the use of the crude drug. The aim of this work was to prepare hybrid molecules presenting a terpene and a quinone moiety and to obtain an assessment of the gastroprotective activity of the new compounds using human cell cultures (MRC-5 fibroblasts and AGS epithelial gastric cells). Eight compounds, including the natural products and semisynthetic derivatives were assessed for proliferation of MRC-5 fibroblasts, protection against sodium taurocholate-induced damage, prostaglandin E2 content, and stimulation of cellular-reduced glutathione synthesis in AGS cells. The following antioxidant assays were performed: DPPH discoloration, scavenging of the superoxide anion, and inhibition of induced lipoperoxidation in erythrocyte membranes. 3-Hydroxy-β-lapachone (3) and cyperenoic acid (4) stimulated fibroblast proliferation. Lapachol (1), dihydroprenyl lapachol (2), 3-hydroxy-β-lapachone (3), and lapachoyl cyperenate (6) protected against sodium taurocholate-induced damage in AGS cells. Lapachol (1) and dihydroprenyl lapachoyl cyperenate (7) significantly stimulated prostaglandin E2 synthesis in AGS cells. Compounds 3, 4, and 7 raised reduced glutathione levels in AGS cells. The hybrid compounds presented activities different than those of the starting sesquiterpene or quinones.

  18. Biolabeling with 2,4-dichlorophenoxyacetic acid derivatives: the 2,4-D tag.

    PubMed

    Bade, Steffen; Röckendorf, Niels; Franek, Milan; Gorris, Hans H; Lindner, Buko; Olivier, Verena; Schaper, Klaus-Jürgen; Frey, Andreas

    2009-12-01

    Many bioanalytic and diagnostic procedures rely on labels with which the molecule of interest can be tracked in or discriminated from accompanying like substances. Herein, we describe a new labeling and detection system based on derivatives of 2,4-dichlorophenoxyacetic acid (2,4-D) and anti-2,4-D antibodies. The 2,4-D system is highly sensitive with a K(D) of 7 x 10(-11) M for the hapten-antibody pair, can be used on a large variety of biomolecules such as proteins, peptides, carbohydrates, and nucleic acids, is not hampered by endogenous backgrounds because 2,4-D is a xenobiotic, and is robust because 2,4-D is a very stable compound that withstands the conditions of most reactions usually performed on biomolecules. With this unique blend of properties, the 2,4-D system compares favorably with its rivals digoxigenin (DIG)/anti-DIG and biotin/(strept)avidin and provides an interesting and powerful tool in biomolecular labeling.

  19. Potential gastroprotective effect of novel cyperenoic acid/quinone derivatives in human cell cultures.

    PubMed

    Theoduloz, Cristina; Carrión, Ivanna Bravo; Pertino, Mariano Walter; Valenzuela, Daniela; Schmeda-Hirschmann, Guillermo

    2012-11-01

    The stem bark of Tabebuia species and the rhizomes of Jatropha isabelii are used in Paraguayan traditional medicine to treat gastric lesions and as anti-inflammatory agents. The sesquiterpene cyperenoic acid obtained from J. isabelii has been shown to display a gastroprotective effect in animal models of induced gastric ulcers while the quinone lapachol shows several biological effects associated with the use of the crude drug. The aim of this work was to prepare hybrid molecules presenting a terpene and a quinone moiety and to obtain an assessment of the gastroprotective activity of the new compounds using human cell cultures (MRC-5 fibroblasts and AGS epithelial gastric cells). Eight compounds, including the natural products and semisynthetic derivatives were assessed for proliferation of MRC-5 fibroblasts, protection against sodium taurocholate-induced damage, prostaglandin E2 content, and stimulation of cellular-reduced glutathione synthesis in AGS cells. The following antioxidant assays were performed: DPPH discoloration, scavenging of the superoxide anion, and inhibition of induced lipoperoxidation in erythrocyte membranes. 3-Hydroxy-β-lapachone (3) and cyperenoic acid (4) stimulated fibroblast proliferation. Lapachol (1), dihydroprenyl lapachol (2), 3-hydroxy-β-lapachone (3), and lapachoyl cyperenate (6) protected against sodium taurocholate-induced damage in AGS cells. Lapachol (1) and dihydroprenyl lapachoyl cyperenate (7) significantly stimulated prostaglandin E2 synthesis in AGS cells. Compounds 3, 4, and 7 raised reduced glutathione levels in AGS cells. The hybrid compounds presented activities different than those of the starting sesquiterpene or quinones. PMID:23047252

  20. Antitrypanosomal Acetylene Fatty Acid Derivatives from the Seeds of Porcelia macrocarpa (Annonaceae).

    PubMed

    de Á Santos, Luciana; Cavalheiro, Alberto J; Tempone, Andre G; Correa, Daniela S; Alexandre, Tatiana R; Quintiliano, Natalia F; Rodrigues-Oliveira, André F; Oliveira-Silva, Diogo; Martins, Roberto Carlos C; Lago, João Henrique G

    2015-05-07

    Chagas' disease is caused by a parasitic protozoan and affects the poorest population in the world, causing high mortality and morbidity. As a result of the toxicity and long duration of current treatments, the discovery of novel and more efficacious drugs is crucial. In this work, the hexane extract from seeds of Porcelia macrocarpa R.E. Fries (Annonaceae) displayed in vitro antitrypanosomal activity against trypomastigote forms of T. cruzi by the colorimetric MTT assay (IC50 of 65.44 μg/mL). Using chromatographic fractionation over SiO2, this extract afforded a fraction composed by one active compound (IC50 of 10.70 µg/mL), which was chemically characterized as 12,14-octadecadiynoic acid (macrocarpic acid). Additionally, two new inactive acetylene compounds (α,α'-dimacro-carpoyl-β-oleylglycerol and α-macrocarpoyl-α'-oleylglycerol) were also isolated from the hexane extract. The complete characterization of the isolated compounds was performed by analysis of NMR and MS data as well as preparation of derivatives.

  1. Biodegradation of novel amino acid derivatives suitable for complexing agents in pulp bleaching applications.

    PubMed

    Metsärinne, Sirpa; Ronkainen, Erja; Tuhkanen, Tuula; Aksela, Reijo; Sillanpää, Mika

    2007-05-01

    The biodegradability of four novel diethanolamine derivative complexing agents was examined by using two biodegradation tests standardised by OECD (301B and 301F). Ethylenediaminetetraacetic acid (EDTA) and diethylenetriaminepentaacetic acid (DTPA) were employed as reference substances. Biodegradation of the new complexing agents was studied both with unacclimated and acclimated inocula as well as by simulating wastewater treatment in sequencing batch reactors (SBRs). These new complexing agents were of technical grade, and therefore, the results are only indicative but these new compounds hold promise for use as complexing agents in the pulp and paper industry. The novel complexing agents were not readily biodegradable but they showed slight biodegradation. Around 10-30% degradation was found in the SBR where degradation was followed by measurement of concentration. Moreover the novel complexing agents did not have any negative impact on reactor performance as measured by chemical oxygen demand reduction. In the standardised biodegradation tests at best around 50% degradation was observed with the acclimated inoculum and in the prolonged test whereas EDTA and DTPA exhibited no biodegradation. The elevated degradation in acclimated sludge indicates that the water treatment plant microbes are capable of decomposing these molecules under favourable conditions. The total concentration of novel complexing agents decreased slightly during biodegradation tests, while the EDTA and DTPA concentrations remained stable. PMID:17346781

  2. Scalable and chromatography-free synthesis of 2-(2-formylalkyl)arenecarboxylic acid derivatives through the supramolecularly controlled hydroformylation of vinylarene-2-carboxylic acids.

    PubMed

    Dydio, Paweł; Reek, Joost N H

    2014-05-01

    This protocol describes how to prepare 2-(2-formylalkyl)-arenecarboxylic acid derivatives, common building blocks for the synthesis of various valuable chemicals (e.g., anti-obesity and Alzheimer's disease treatment pharmaceuticals), by using the fully regioselective hydroformylation of vinyl arene derivatives. This catalytic reaction proceeds cleanly with 100% regioselectivity and chemoselectivity. The procedure is reliably scalable and can be efficiently conducted on a multigram scale. The analytically pure product is easily isolated with a nearly quantitative yield by using a simple acid-base extraction workup and avoids any tedious chromatography. This protocol details the synthesis of a bisphosphite ligand (L1) that is a pivotal element of the catalytic system used, Rh(acac)(CO)2 with ligand L1, starting from commercial building blocks. The protocol also describes a general procedure for the preparative hydroformylation of vinylarene-2-carboxylic acid derivatives to 2-formylalkylarene products, providing a representative example for the hydroformylation of 2-vinylbenzoic acid (1a) to 2-(3-oxopropane)-benzoic acid (2a). The synthesis of L1 (six chemical reactions) uses 2-nitrophenylhydrazine, 4-benzyloxybenzoylchloride and (S)-binol, and takes 5-7 working days. The actual hydroformylation reaction of each vinyl arene derivative takes ∼4 h of active effort over a period of 1-3 d. PMID:24762785

  3. Scalable and chromatography-free synthesis of 2-(2-formylalkyl)arenecarboxylic acid derivatives through the supramolecularly controlled hydroformylation of vinylarene-2-carboxylic acids.

    PubMed

    Dydio, Paweł; Reek, Joost N H

    2014-05-01

    This protocol describes how to prepare 2-(2-formylalkyl)-arenecarboxylic acid derivatives, common building blocks for the synthesis of various valuable chemicals (e.g., anti-obesity and Alzheimer's disease treatment pharmaceuticals), by using the fully regioselective hydroformylation of vinyl arene derivatives. This catalytic reaction proceeds cleanly with 100% regioselectivity and chemoselectivity. The procedure is reliably scalable and can be efficiently conducted on a multigram scale. The analytically pure product is easily isolated with a nearly quantitative yield by using a simple acid-base extraction workup and avoids any tedious chromatography. This protocol details the synthesis of a bisphosphite ligand (L1) that is a pivotal element of the catalytic system used, Rh(acac)(CO)2 with ligand L1, starting from commercial building blocks. The protocol also describes a general procedure for the preparative hydroformylation of vinylarene-2-carboxylic acid derivatives to 2-formylalkylarene products, providing a representative example for the hydroformylation of 2-vinylbenzoic acid (1a) to 2-(3-oxopropane)-benzoic acid (2a). The synthesis of L1 (six chemical reactions) uses 2-nitrophenylhydrazine, 4-benzyloxybenzoylchloride and (S)-binol, and takes 5-7 working days. The actual hydroformylation reaction of each vinyl arene derivative takes ∼4 h of active effort over a period of 1-3 d.

  4. Rational design of 5-aminolevulinic acid derivatives aimed at improving photodynamic therapy.

    PubMed

    Casas, Adriana; Batlle, Alcira

    2002-07-01

    5-aminolevulinic acid (ALA) is the first intermediate in heme biosynthesis and is therefore a precursor of protoporphyrin IX (PpIX). PpIX is used as an endogenous photosensitizer in photodynamic therapy (PDT). Several chemical modifications have been made, both on the amino and carboxyl groups of ALA to induce higher PpIX production and photosensitisation. Esterification of ALA with aliphatic lineal and cyclic alcohols was found to reduce the amount of ALA required for photosensitization. Esterification by aliphatic alcohols with carbohydrate chains equal or lower than C4 leads to porphyrin accumulation lower than ALA, whereas equal or longer than C6 chains leads to greater synthesis of porphyrin. A branch point in the alcohol located next to the site of ester cleavage limits access of the esters to the esterase active site, resulting in lower PpIX production. ALA esters of the polyethylenglycol family can induce high levels of PpIX, with some selectivity for endothelial cells toward tumor cells. On the basis of the differential expression of some aminopeptidases in tumor vasculature when compared to normal vasculature, some ALA-pseudopeptides were synthesized. In a rational design of ALA derivatives, the transport mechanism of these aminoacids into the cell is central. Due to the similar characteristics between ALA and GABA transport, a novel approach for designing new ALA derivatives which could penetrate more easily into tumoral cells, would be to take into account the structures of the inhibitors of GABA transport. PMID:12678731

  5. Synthesis of heterocycle-modified betulinic acid derivatives as antitumor agents.

    PubMed

    Cui, Hai-Wei; He, Yuan; Wang, Jinhua; Gao, Wei; Liu, Ting; Qin, Min; Wang, Xue; Gao, Cheng; Wang, Yan; Liu, Ming-Yao; Yi, Zhengfang; Qiu, Wen-Wei

    2015-05-01

    A series of novel heterocycle-modified betulinic acid (BA) derivatives were synthesized and investigated for their activity against the growth of eight non-drug resistant and one multidrug-resistant tumor cell line using a sulforhodamine B (SRB) assay. The most active compound 17 showed an average IC50 1.19 μM, which was about 20 times more potent than the lead compound BA. It is amazing that for most synthetic saturated N-heterocycle derivatives, MCF-7/ADR was the most sensitive tumor cells, especially 17 showed the most potent antitumor activity (IC50 = 0.33 μM) on this multidrug-resistant tumor cell line, that was 117 times more potent than BA. Most of the tested compounds displayed less toxic on human fibroblasts (HAF) in comparison with the tumor cell lines. The cytometry and transwell migration assays were used to test the ability of 17 to induce apoptosis and inhibit metastasis on tumor cell lines respectively.

  6. Anti-hepatoma activity and mechanism of ursolic acid and its derivatives isolated from Aralia decaisneana

    PubMed Central

    Tian, Ze; Lin, Geng; Zheng, Rui-Xia; Huang, Feng; Yang, Meng-Su; Xiao, Pei-Gen

    2006-01-01

    AIM: To investigate the anti-tumor activity of ursolic acid (UA) and its derivatives isolated from Aralia decaisneana on hepatocellular carcinoma both in vitro and in vivo. METHODS: In vivo cytotoxicity was first screened by 3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay. Morphological observation, DNA ladder, flow cytometry analysis, Western blot and real time PCR were employed to elucidate the cytotoxic mechanism of UA. Implanted mouse hepatoma H22 was used to evaluate the growth inhibitory effect of UA in vivo. RESULTS: UA could significantly inhibit the proliferation of HepG2 and its drug-resistance strain, R-HepG2 cells, but had no inhibitory effect on primarily cultured normal mouse hepatocytes whereas all the six derivatives of UA could not inhibit the growth of all tested cell lines. Further study on mechanism demonstrated that apoptosis and G0/G1 arrest were involved in the cytotoxicity and cleavage of poly-(ADP-ribose)-polymerase (PARP). Downregulation of cyclooxygenase-2 (COX-2) protein and upregulation of heat shock protein (HSP) 105 mRNA correlated to the apoptosis of HepG2 cells treated with UA. In addition, UA also could inhibit the growth of H22 hepatoma in vivo. CONCLUSION: UA is a promising anti-tumor agent, but further work needs to be done to improve its solubility. PMID:16521214

  7. Fatty Acid-Derived Pro-Toxicants of the Rat Selective Toxicant Norbormide.

    PubMed

    Choi, Hans; Conole, Daniel; Atkinson, Darcy J; Laita, Olivia; Jay-Smith, Morgan; Pagano, Mario Angelo; Ribaudo, Giovanni; Cavalli, Maurizio; Bova, Sergio; Hopkins, Brian; Brimble, Margaret A; Rennison, David

    2016-06-01

    Norbormide [5-(α-hydroxy-α-2-pyridylbenzyl)-7-(α-2-pyridylbenzylidene)-5-norbornene-2,3-dicarboximide] (NRB), an existing but infrequently used rodenticide, is known to be uniquely toxic to rats but relatively harmless to other rodents and mammals. However, as an acute vasoactive, NRB has a rapid onset of action which makes it relatively unpalatable to rats, often leading to sublethal uptake and accompanying bait shyness. A series of NRB-derived pro-toxicants (3a - i, 4a - i, and 5a - i) were prepared in an effort to 'mask' this acute response and improve both palatability and efficacy. Their synthesis, in vitro biological evaluation (vasocontractile response in rat vasculature, stability in selected rat media) and palatability/efficacy in Sprague-Dawley, wild Norway, and wild ship rats is described. Most notably, pro-toxicant 3d was revealed to be free of all pre-cleavage vasoconstrictory activity in rat caudal artery and was subsequently demonstrated to release NRB in the presence of rat blood, liver, and pancreatic enzymes. Moreover, it consistently displayed a high level of acceptance by rats in a two-choice bait-palatability and efficacy trial, with accompanying high mortality. On this evidence, fatty acid ester prodrugs would appear to offer a promising platform for the further development of NRB-derived toxicants with enhanced palatability and efficacy profiles. PMID:27144301

  8. Synthesis, characterization, and evaluation of 10-undecenoic acid-based epithio derivatives as multifunctional additives.

    PubMed

    Geethanjali, Gorla; Padmaja, Korlipara V; Sammaiah, Arukali; Prasad, Rachapudi B N

    2014-11-26

    Novel epithio compounds from alkyl epoxy undecanoates (n-alkyl, C1, C4, and C6; isoalkyl, C3, C4, and C8) were synthesized using an ammonium thiocyanate in ionic liquid 1-methylimidazolium tetrafluoroborate/H2O (2:1) solvent system in 85-90% yields by gas chromatographic (GC) analysis. The synthesized products were characterized by (1)H and (13)C nuclear magnetic resonance spectroscopy, Fourier transform infrared spectroscopy (FTIR), gas chromatography, and GC mass spectral (GC-MS) analyses and evaluated for their antioxidant, extreme pressure (EP), and antiwear (AW) properties in three different base oils, namely, epoxy jatropha fatty acid n-butyl esters (EJB), di-2-ethylhexyl sebacate (DOS), and mineral oil (S-105). Among the synthesized products, n-butyl epithio undecanoate exhibited superior antioxidant property (229.2 °C) compared to butylated hydroxytoluene (BHT, 193.8 °C) in base oil DOS and comparable performance in EJB and S-105 base oils. All of the epithio derivatives exhibited significantly enhanced weld point for the base oils EJB and DOS at 2 wt % level and displayed moderate enhancement in S-105 base oil. Methyl epithio undecanoate at 0.6% concentration exhibited considerable improvement in the wear scar of DOS base oil. The synthesized epithio derivatives have potential as multifunctional additives in lubricant formulations.

  9. Fibroblastic reticular cell-derived lysophosphatidic acid regulates confined intranodal T-cell motility

    PubMed Central

    Takeda, Akira; Kobayashi, Daichi; Aoi, Keita; Sasaki, Naoko; Sugiura, Yuki; Igarashi, Hidemitsu; Tohya, Kazuo; Inoue, Asuka; Hata, Erina; Akahoshi, Noriyuki; Hayasaka, Haruko; Kikuta, Junichi; Scandella, Elke; Ludewig, Burkhard; Ishii, Satoshi; Aoki, Junken; Suematsu, Makoto; Ishii, Masaru; Takeda, Kiyoshi; Jalkanen, Sirpa; Miyasaka, Masayuki; Umemoto, Eiji

    2016-01-01

    Lymph nodes (LNs) are highly confined environments with a cell-dense three-dimensional meshwork, in which lymphocyte migration is regulated by intracellular contractile proteins. However, the molecular cues directing intranodal cell migration remain poorly characterized. Here we demonstrate that lysophosphatidic acid (LPA) produced by LN fibroblastic reticular cells (FRCs) acts locally to LPA2 to induce T-cell motility. In vivo, either specific ablation of LPA-producing ectoenzyme autotaxin in FRCs or LPA2 deficiency in T cells markedly decreased intranodal T cell motility, and FRC-derived LPA critically affected the LPA2-dependent T-cell motility. In vitro, LPA activated the small GTPase RhoA in T cells and limited T-cell adhesion to the underlying substrate via LPA2. The LPA-LPA2 axis also enhanced T-cell migration through narrow pores in a three-dimensional environment, in a ROCK-myosin II-dependent manner. These results strongly suggest that FRC-derived LPA serves as a cell-extrinsic factor that optimizes T-cell movement through the densely packed LN reticular network. DOI: http://dx.doi.org/10.7554/eLife.10561.001 PMID:26830463

  10. Diversity of exophillic acid derivatives in strains of an endophytic Exophiala sp.

    PubMed

    Cheikh-Ali, Zakaria; Glynou, Kyriaki; Ali, Tahir; Ploch, Sebastian; Kaiser, Marcel; Thines, Marco; Bode, Helge B; Maciá-Vicente, Jose G

    2015-10-01

    Members of the fungal genus Exophiala are common saprobes in soil and water environments, opportunistic pathogens of animals, or endophytes in plant roots. Their ecological versatility could imply a capacity to produce diverse secondary metabolites, but only a few studies have aimed at characterizing their chemical profiles. Here, we assessed the secondary metabolites produced by five Exophiala sp. strains of a particular phylotype, isolated from roots of Microthlaspi perfoliatum growing in different European localities. Exophillic acid and two previously undescribed compounds were isolated from these strains, and their structures were elucidated by spectroscopic methods using MS, 1D and 2D NMR. Bioassays revealed a weak activity of these compounds against disease-causing protozoa and mammalian cells. In addition, 18 related structures were identified by UPLC/MS based on comparisons with the isolated structures. Three Exophiala strains produced derivatives containing a β-d-glucopyranoside moiety, and their colony morphology was distinct from the other two strains, which produced derivatives lacking β-d-glucopyranoside. Whether the chemical/morphological strain types represent variants of the same genotype or independent genetic populations within Exophiala remains to be evaluated. PMID:26296744

  11. In vitro skin permeation and retention of 5-aminolevulinic acid ester derivatives for photodynamic therapy.

    PubMed

    De Rosa, Fernanda Scarmato; Tedesco, Antônio Cláudio; Lopez, Renata Fonseca Vianna; Pierre, Maria Bernadete Riemma; Lange, Norbert; Marchetti, Juliana Maldonado; Rotta, Jeane Cristina Gomes; Bentley, Maria Vitória Lopes Badra

    2003-04-29

    In photodynamic therapy (PDT), 5-aminiolevulinic acid (5-ALA) applied topically is converted, via the heme cycle, into protoporphyrin IX (PpIX), a photosensitizing agent, which upon excitation with light can induce tumor destruction. Due to its hydrophilic and zwitterionic characteristics, 5-ALA has limited penetration into the skin. More lipophilic 5-ALA ester derivatives are expected to cross stratum corneum more easily than 5-ALA. According to the determination of the partition coefficients of 5-ALA methyl, n-butyl, n-hexyl and n-octyl esters, these compounds showed an increased affinity to the SC, with 5-ALA hexyl ester and 5-ALA-octyl ester having the highest partition coefficients. Our in vitro skin permeation studies demonstrated an increased permeated amount for hexyl-ALA after 6 h of incubation, compared to other esters and 5-ALA. After 6 h, more 5-ALA-hexyl ester and -octyl ester were retained at viable epidermis and dermis than 5-ALA. According to these results, and considering that the conversion of 5-ALA into PpIX occurs preferentially in epidermis, it can be supposed that topical use of ester derivatives with longer chains (C(6) or C(8)) is an interesting proposal to optimize topical 5-ALA-PDT

  12. Human GAPDH Is a Target of Aspirin's Primary Metabolite Salicylic Acid and Its Derivatives.

    PubMed

    Choi, Hyong Woo; Tian, Miaoying; Manohar, Murli; Harraz, Maged M; Park, Sang-Wook; Schroeder, Frank C; Snyder, Solomon H; Klessig, Daniel F

    2015-01-01

    The plant hormone salicylic acid (SA) controls several physiological processes and is a key regulator of multiple levels of plant immunity. To decipher the mechanisms through which SA's multiple physiological effects are mediated, particularly in immunity, two high-throughput screens were developed to identify SA-binding proteins (SABPs). Glyceraldehyde 3-Phosphate Dehydrogenase (GAPDH) from plants (Arabidopsis thaliana) was identified in these screens. Similar screens and subsequent analyses using SA analogs, in conjunction with either a photoaffinity labeling technique or surface plasmon resonance-based technology, established that human GAPDH (HsGAPDH) also binds SA. In addition to its central role in glycolysis, HsGAPDH participates in several pathological processes, including viral replication and neuronal cell death. The anti-Parkinson's drug deprenyl has been shown to suppress nuclear translocation of HsGAPDH, an early step in cell death and the resulting cell death induced by the DNA alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine. Here, we demonstrate that SA, which is the primary metabolite of aspirin (acetyl SA) and is likely responsible for many of its pharmacological effects, also suppresses nuclear translocation of HsGAPDH and cell death. Analysis of two synthetic SA derivatives and two classes of compounds from the Chinese medicinal herb Glycyrrhiza foetida (licorice), glycyrrhizin and the SA-derivatives amorfrutins, revealed that they not only appear to bind HsGAPDH more tightly than SA, but also exhibit a greater ability to suppress translocation of HsGAPDH to the nucleus and cell death.

  13. Amino Acid Derivatives as Bitter Taste Receptor (T2R) Blockers*

    PubMed Central

    Pydi, Sai P.; Sobotkiewicz, Tyler; Billakanti, Rohini; Bhullar, Rajinder P.; Loewen, Michele C.; Chelikani, Prashen

    2014-01-01

    In humans, the 25 bitter taste receptors (T2Rs) are activated by hundreds of structurally diverse bitter compounds. However, only five antagonists or bitter blockers are known. In this study, using molecular modeling guided site-directed mutagenesis, we elucidated the ligand-binding pocket of T2R4. We found seven amino acids located in the extracellular side of transmembrane 3 (TM3), TM4, extracellular loop 2 (ECL2), and ECL3 to be involved in T2R4 binding to its agonist quinine. ECL2 residues Asn-173 and Thr-174 are essential for quinine binding. Guided by a molecular model of T2R4, a number of amino acid derivatives were screened for their ability to bind to T2R4. These predictions were tested by calcium imaging assays that led to identification of γ-aminobutryic acid (GABA) and Nα,Nα-bis(carboxymethyl)-l-lysine (BCML) as competitive inhibitors of quinine-activated T2R4 with an IC50 of 3.2 ± 0.3 μm and 59 ± 18 nm, respectively. Interestingly, pharmacological characterization using a constitutively active mutant of T2R4 reveals that GABA acts as an antagonist, whereas BCML acts as an inverse agonist on T2R4. Site-directed mutagenesis confirms that the two novel bitter blockers share the same orthosteric site as the agonist quinine. The signature residues Ala-90 and Lys-270 play important roles in interacting with BCML and GABA, respectively. This is the first report to characterize a T2R endogenous antagonist and an inverse agonist. The novel bitter blockers will facilitate physiological studies focused on understanding the roles of T2Rs in extraoral tissues. PMID:25059668

  14. Unsaturated amino acids derived from isoleucine trigger early membrane effects on plant cells.

    PubMed

    Roblin, Gabriel; Laduranty, Joëlle; Bonmort, Janine; Aidene, Mohand; Chollet, Jean-François

    2016-10-01

    Unsaturated amino acids (UnsAA) have been shown to affect the activity of various biological processes. However, their mode of action has been investigated poorly thus far. We show in this work that 2-amino-3-methyl-4-pentenoic acid (C2) and 2-amino-3-methyl-4-pentynoic acid (C3) structurally derived from isoleucine (Ile) exhibited a multisite action on plant cells. For one, C2 and C3 induced early modifications at the plasma membrane level, as shown by the hyperpolarization monitored by microelectrode implantation in the pulvinar cells of Mimosa pudica, indicating that these compounds are able to modify ionic fluxes. In particular, proton (H(+)) fluxes were modified, as shown by the pH rise monitored in the bathing medium of pulvinar tissues. A component of this effect may be linked to the inhibitory effect observed on the proton pumping and the vanadate-sensitive activity of the plasma membrane H(+)-ATPase monitored in plasma membrane vesicles (PMVs) purified from pulvinar tissues of M. pudica and leaf tissues of Beta vulgaris. This effect may explain, in part, the inhibitory effect of the compounds on the uptake capacity of sucrose and valine by B. vulgaris leaf tissues. In contrast, an unexpected action was observed in cell reactions, implicating ion fluxes and water movement. Indeed, the osmocontractile reactions of pulvini induced either by a mechanical shock in M. pudica or by dark and light signals in Cassia fasciculata were increased, indicating that, compared to Ile, these compounds may modify in a specific way the plasma membrane permeability to water and ions. PMID:27254795

  15. Electrochemical discrimination of phthalic acid among three phthalic acid isomers based on an N-butylaminomethyl-ferrocene derivative.

    PubMed

    Yoon, Jisoo; Jadhav, Jyoti Ramesh; Kim, Jun Myung; Cheong, Minserk; Kim, Hong-Seok; Kim, Joohoon

    2014-07-21

    A chemosensor compound (1) consisting of a central ferrocene with two butylaminomethyl arms showed unexpected facile electrochemical oxidation of the secondary amines in proximity to the ferrocene, which was utilized for electrochemical discrimination of phthalic acid selectively over two other isomers, isophthalic acid and terephthalic acid.

  16. The maize death acids, 10-oxo-11-phytoenoic acid and derivatives, demonstrate specificity in jasmonate-related signaling and defense

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Plant cellular damage promotes the interaction of lipoxygenases (LOX) with free fatty acids to yield 9- and 13-hydroperoxides which are further metabolized into diverse oxylipins. The enzymatic action of 13-LOX on linolenic acid enables production of 12-oxo-phytodienoic acid (12-OPDA) and its downst...

  17. Synthesis, cytotoxic evaluation and in silico pharmacokinetic prediction of some benzo[a]phenazine-5-sulfonic acid derivatives.

    PubMed

    Hari Narayana Moorthy, N S; Karthikeyan, C; Trivedi, Piyush

    2009-11-01

    Cancer is one of the life threatening diseases and the development of novel anticancer molecules is limited by many reasons. In the present investigation, some novel benzo[a]phenazine-5-sulfonic acid derivatives as DNA intercalator was designed with optimized pharmacokinetic features for cancer treatment. The compounds with desired pharmacokinetic profile were synthesized and structurally characterized. Cytotoxic activity study against HL-60 tumor cell lines shows that 10-dimethyl carboxamido derivative of benzo[a]phenazine-5-sulfonic acid is found to be the most active in the series with cytotoxic activity (IC(50) = 19 microM) comparable to cisplatin (IC(50) = 7 microM). The study concluded that the novel benzo[a]phenazine-5-sulfonic acid derivatives were found to have enhanced DNA binding affinity and exhibited significant activity in vitro against HL-60 cell lines. This work will also guide for further development of effective DNA intercalators for cancer treatment.

  18. Oleanolic acid and its synthetic derivatives for the prevention and therapy of cancer: Preclinical and clinical evidence

    PubMed Central

    Shanmugam, Muthu K.; Dai, Xiaoyun; Kumar, Alan Prem; Tan, Benny KH; Sethi, Gautam; Bishayee, Anupam

    2014-01-01

    Oleanolic acid (OA, 3β-hydroxyolean-12-en-28-oic acid) is a ubiquitous pentacyclic multifunctional triterpenoid, widely found in several dietary and medicinal plants. Natural and synthetic OA derivatives can modulate multiple signaling pathways including nuclear factor-κB, AKT, signal transducer and activator of transcription 3, mammalian target of rapamycin, caspases, intercellular adhesion molecule 1, vascular endothelial growth factor, and poly (ADP-ribose) polymerase in a variety of tumor cells. Importantly, synthetic derivative of OA, 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO), and its C-28 methyl ester (CDDO-Me) and C28 imidazole (CDDO-Im) have demonstrated potent antiangiogenic and antitumor activities in rodent cancer models. These agents are presently under evaluation in phase I studies in cancer patients. This review summarizes the diverse molecular targets of OA and its derivatives and also provides clear evidence on their promising potential in preclinical and clinical situations. PMID:24486850

  19. Penicacids A-C, three new mycophenolic acid derivatives and immunosuppressive activities from the marine-derived fungus Penicillium sp. SOF07.

    PubMed

    Chen, Ziming; Zheng, Zhihui; Huang, Hongbo; Song, Yongxiang; Zhang, Xuelian; Ma, Junying; Wang, Bo; Zhang, Changsheng; Ju, Jianhua

    2012-05-01

    Three new mycophenolic acid derivatives, penicacids A-C (1-3), together with two known analogues, mycophenolic acid (MPA, 4) and 4'-hydroxy-MPA (5), were isolated from a fungus Penicillium sp. SOF07 derived from a South China Sea marine sediment. The structures of compounds 1-3 were elucidated on the basis of MS and NMR ((1)H, (13)C, HSQC and HMBC) data analyses and comparisons with the known compounds. Structure-activity relationship studies of compounds 1-5 focused on inosine-monophosphate dehydrogenase inhibition revealed that hydroxylation at C-4', methylation at C-7-OH, dual hydroxylation at C-2'/C-3' double bond of MPA diminished bioactivity whereas glucosyl hydroxylation at C-4' correlated to bioactivity comparable to that observed for MPA.

  20. The antimicrobial efficacy and structure activity relationship of novel carbohydrate fatty acid derivatives against Listeria spp. and food spoilage microorganisms.

    PubMed

    Nobmann, Patricia; Smith, Aoife; Dunne, Julie; Henehan, Gary; Bourke, Paula

    2009-01-15

    Novel mono-substituted carbohydrate fatty acid (CFA) esters and ethers were investigated for their antibacterial activity against a range of pathogenic and spoilage bacteria focussing on Listeria monocytogenes. Carbohydrate derivatives with structural differences enable comparative studies on the structure/activity relationship for antimicrobial efficacy and mechanism of action. The antimicrobial efficacy of the synthesized compounds was compared with commercially available compounds such as monolaurin and monocaprylin, as well as the pure free fatty acids, lauric acid and caprylic acid, which have proven antimicrobial activity. Compound efficacy was compared using an absorbance based broth microdilution assay to determine the minimum inhibitory concentration (MIC), increase in lag phase and decrease in maximum growth rate. Among the carbohydrate derivatives synthesized, lauric ether of methyl alpha-d-glucopyranoside and lauric ester of methyl alpha-d-mannopyranoside showed the highest growth-inhibitory effect with MIC values of 0.04 mM, comparable to monolaurin. CFA derivatives were generally more active against Gram positive bacteria than Gram negative bacteria. The analysis of both ester and ether fatty acid derivatives of the same carbohydrate, in tandem with alpha and beta configuration of the carbohydrate moiety suggest that the carbohydrate moiety is involved in the antimicrobial activity of the fatty acid derivatives and that the nature of the bond also has a significant effect on efficacy, which requires further investigation. This class of CFA derivatives has great potential for developing antibacterial agents relevant to the food industry, particularly for control of Listeria or other Gram-positive pathogens.

  1. Reduction of hydrogen peroxide stress derived from fatty acid beta-oxidation improves fatty acid utilization in Escherichia coli.

    PubMed

    Doi, Hidetaka; Hoshino, Yasushi; Nakase, Kentaro; Usuda, Yoshihiro

    2014-01-01

    Fatty acids are a promising raw material for substance production because of their highly reduced and anhydrous nature, which can provide higher fermentation yields than sugars. However, they are insoluble in water and are poorly utilized by microbes in industrial fermentation production. We used fatty acids as raw materials for L-lysine fermentation by emulsification and improved the limited fatty acid-utilization ability of Escherichia coli. We obtained a fatty acid-utilizing mutant strain by laboratory evolution and demonstrated that it expressed lower levels of an oxidative-stress marker than wild type. The intracellular hydrogen peroxide (H₂O₂) concentration of a fatty acid-utilizing wild-type E. coli strain was higher than that of a glucose-utilizing wild-type E. coli strain. The novel mutation rpsA(D210Y) identified in our fatty acid-utilizing mutant strain enabled us to promote cell growth, fatty-acid utilization, and L-lysine production from fatty acid. Introduction of this rpsA(D210Y) mutation into a wild-type strain resulted in lower H₂O₂ concentrations. The overexpression of superoxide dismutase (sodA) increased intracellular H₂O₂ concentrations and inhibited E. coli fatty-acid utilization, whereas overexpression of an oxidative-stress regulator (oxyS) decreased intracellular H₂O₂ concentrations and promoted E. coli fatty acid utilization and L-lysine production. Addition of the reactive oxygen species (ROS) scavenger thiourea promoted L-lysine production from fatty acids and decreased intracellular H₂O₂ concentrations. Among the ROS generated by fatty-acid β-oxidation, H₂O₂ critically affected E. coli growth and L-lysine production. This indicates that the regression of ROS stress promotes fatty acid utilization, which is beneficial for fatty acids used as raw materials in industrial production. PMID:24169950

  2. Improvement of catalytic activity of lipase in the presence of calix[4]arene valeric acid or hydrazine derivative.

    PubMed

    Akoz, Enise; Sayin, Serkan; Kaplan, Selcuk; Yilmaz, Mustafa

    2015-03-01

    Sol-gel encapsulation is a simple but powerful method to enhance the enantioselectivity of lipase-catalyzed transformations in an isooctane/aqueous buffer solution. Candida rugosa lipase was encapsulated according to a sol-gel procedure in the presence and absence of calix[4]arene hydrazine or carboxylic acid derivatives with Fe3O4 magnetic nanoparticles as an additive. The activity of the encapsulated lipases was evaluated for the enantioselective hydrolysis of racemic Naproxen methyl ester and the hydrolysis of p-Nitrophenylpalmitate. The results indicate that the encapsulated lipase without calix[4]arene derivative has lower conversion and enantioselectivity compared to the encapsulated lipase with calix[4]arene derivative. It was found that the calix[4]arene hydrazine and carboxylic acid-based encapsulated lipases have excellent activity and enantioselectivity (E >300) compared to encapsulated lipase without the calix[4]arene derivatives.

  3. Amphipathic β2,2-Amino Acid Derivatives Suppress Infectivity and Disrupt the Intracellular Replication Cycle of Chlamydia pneumoniae

    PubMed Central

    Tiirola, Terttu M.; Strøm, Morten B.; Vuorela, Pia M.

    2016-01-01

    We demonstrate in the current work that small cationic antimicrobial β2,2-amino acid derivatives (Mw < 500 Da) are highly potent against Chlamydia pneumoniae at clinical relevant concentrations (< 5 μM, i.e. < 3.4 μg/mL). C. pneumoniae is an atypical respiratory pathogen associated with frequent treatment failures and persistent infections. This gram-negative bacterium has a biphasic life cycle as infectious elementary bodies and proliferating reticulate bodies, and efficient treatment is challenging because of its long and obligate intracellular replication cycle within specialized inclusion vacuoles. Chlamydicidal effect of the β2,2-amino acid derivatives in infected human epithelial cells was confirmed by transmission electron microscopy. Images of infected host cells treated with our lead derivative A2 revealed affected chlamydial inclusion vacuoles 24 hours post infection. Only remnants of elementary and reticulate bodies were detected at later time points. Neither the EM studies nor resazurin-based cell viability assays showed toxic effects on uninfected host cells or cell organelles after A2 treatment. Besides the effects on early intracellular inclusion vacuoles, the ability of these β2,2-amino acid derivatives to suppress Chlamydia pneumoniae infectivity upon treatment of elementary bodies suggested also a direct interaction with bacterial membranes. Synthetic β2,2-amino acid derivatives that target C. pneumoniae represent promising lead molecules for development of antimicrobial agents against this hard-to-treat intracellular pathogen. PMID:27280777

  4. Synthetic thioamide, benzimidazole, quinolone and derivatives with carboxylic acid and ester moieties: a strategy in the design of antituberculosis agents.

    PubMed

    Ashfaq, M; Shah, S S A; Najam, T; Ahmad, M M; Tabassum, R; Rivera, G

    2014-03-01

    Synthetic heterocyclic compounds have remarkable potential activity against diseases; thioamides, benzimidazoles, quinolones and derivatives with carboxylic acid and esters moieties have shown excellent activity against Mycobacterium tuberculosis. We reviewed antituberculosis activities of above compounds with reference to half maximal inhibitory concentration, minimum inhibitory concentration and structural-activity relationship which clearly indicate that electron-withdrawing groups are the main inducers of antimycobacterium activity. Comparison between clinically used drugs and new synthetic derivatives showed recent advances made in the last decade.

  5. Facile synthesis of enantioenriched Cγ-tetrasubstituted α-amino acid derivatives via an asymmetric nucleophilic addition/protonation cascade.

    PubMed

    Duan, Shu-Wen; An, Jing; Chen, Jia-Rong; Xiao, Wen-Jing

    2011-05-01

    An asymmetric nucleophilic addition/protonation reaction of 3-substituted oxindoles and ethyl 2-phthalimidoacrylate has been described. This strategy can give direct access to C(γ)-tetrasubstituted α-amino acid derivatives bearing 1,3-nonadjacent stereocenters with up to 98% yield, 94:6 dr, and >99% ee. Dual activation is proposed in the transition state, and the opposite enantiomers can be obtained simply by changing cinchonidine-derived catalyst to the cinchonine analogue.

  6. Impact of lipid oxidation-derived aldehydes and ascorbic acid on the antioxidant activity of model melanoidins.

    PubMed

    Kitrytė, Vaida; Adams, An; Venskutonis, Petras Rimantas; De Kimpe, Norbert

    2012-12-01

    As the heat-induced formation of antioxidants throughout the Maillard reaction is known, this study was undertaken to evaluate the impact of lipid oxidation-derived aldehydes and ascorbic acid in Maillard model systems on the resulting antioxidant activity. For this purpose, various fractions of melanoidin-like polycondensation products were obtained from mixtures of amino acids (glycine, lysine, arginine) and lipid oxidation-derived aldehydes (hexanal, (E)-2-hexenal), in the presence or absence of glucose or ascorbic acid. All fractions showed a significant radical scavenging capacity (DPPH assay) and ferric reducing power (FRAP assay). The activity varied according to the composition of the model system tested, although some similar trends were discovered in both assays applied. The presence of lipid oxidation products in the browning products augmented the antioxidant activity in specific cases. For instance, the combined presence of arginine, hexanal and glucose in heated model systems resulted in a significantly higher antioxidant capacity. With an exception of ascorbic acid-containing model systems, melanoidin-like polycondensation products possessed significantly stronger antioxidant activities than the corresponding unheated initial reactant mixtures. Water-soluble high molecular weight (>12kDa) and nonsoluble fractions comprised the major part of the antioxidants derived from amino acid/lipid oxidation product model systems, with or without glucose or ascorbic acid. PMID:22953854

  7. n-3 fatty acid-derived lipid mediators in the brain: new weapons against oxidative stress and inflammation.

    PubMed

    Farooqui, A A

    2012-01-01

    Neuroprotectins, resolvins, and maresins are subfamilies of endogenous oxygenated metabolites derived from n-3 or ω-3 fatty acids (eicosapentaenoic and docosahexaenoic acids). These metabolites are associated with signal transduction processes involved in downregulation of oxidative stress, neuroinflammation and apoptosis. Eicosapentaenoic acid-derived E-series resolvins (RvE₁ and RvE₂) and docosahexaenoic acid-derived D-series resolvins (RvD₁ and RvD₂) and neuroprotectins have potent anti-inflammatory and proresolution, and antioxidant properties. They not only retard excessive inflammatory process, but also promote resolution by enhancing clearance of apoptotic cells and debris from inflamed brain tissue and vasculature leading to tissue homeostasis. These actions may underlie the beneficial effects of eicosapentaenoic acid and docosahexaenoic acid in normal human health, neurotraumatic and neurodegenerative diseases. Aspirin initiates resolution not only by exerting antithrombotic actions, but also triggering biosynthesis of specific and stereoselective epimers of resolvins, protectins, and maresins. In addition during the onset of resolution, these lipid mediators also display potent protective roles in neural systems, liver, lungs, and eyes. Potent anti-inflammatory actions of resolvins, and protectins in models of chronic human diseases indicate that down-regulation in resolution pathways may contribute to the decrease in the intensity of many chronic neurodegenerative and visceral diseases. PMID:22204329

  8. Solution properties and emulsification properties of amino acid-based gemini surfactants derived from cysteine.

    PubMed

    Yoshimura, Tomokazu; Sakato, Ayako; Esumi, Kunio

    2013-01-01

    Amino acid-based anionic gemini surfactants (2C(n)diCys, where n represents an alkyl chain with a length of 10, 12, or 14 carbons and "di" and "Cys" indicate adipoyl and cysteine, respectively) were synthesized using the amino acid cysteine. Biodegradability, equilibrium surface tension, and dynamic light scattering were used to characterize the properties of gemini surfactants. Additionally, the effects of alkyl chain length, number of chains, and structure on these properties were evaluated by comparing previously reported gemini surfactants derived from cystine (2C(n)Cys) and monomeric surfactants (C(n)Cys). 2C(n)diCys shows relatively higher biodegradability than does C(n)Cys and previously reported sugar-based gemini surfactants. Both critical micelle concentration (CMC) and surface tension decrease when alkyl chain length is increased from 10 to 12, while a further increase in chain length to 14 results in increased CMC and surface tension. This indicates that long-chain gemini surfactants have a decreased aggregation tendency due to the steric hindrance of the bulky spacer as well as premicelle formation at concentrations below the CMC and are poorly packed at the air/water interface. Formation of micelles (measuring 2 to 5 nm in solution) from 2C(n)diCys shows no dependence on alkyl chain length. Further, shaking the mixtures of aqueous 2C(n)diCys surfactant solutions and squalane results in the formation of oil-in-water type emulsions. The highly stable emulsions are formed using 2C₁₂diCys or 2C₁₄diCys solution and squalane in a 1:1 or 2:1 volume ratio.

  9. A proapoptotic effect of valproic acid on progenitors of embryonic stem cell-derived glutamatergic neurons

    PubMed Central

    Fujiki, R; Sato, A; Fujitani, M; Yamashita, T

    2013-01-01

    Valproic acid (VPA) is a branched-chain saturated fatty acid with a long history of clinical use as an antiepileptic drug (AED). VPA is also known to inhibit histone deacetylases (HDACs) and to cause diverse effects on neural progenitor cells (NPCs) and neurons. Although the neuroprotective or neurodestructive effects of VPA have been investigated in heterogeneous cell populations, in this study, we used homogeneous populations of NPCs and glutamatergic cortical pyramidal neurons, which were differentiated from embryonic stem (ES) cells. At therapeutic concentrations, VPA had a proapoptotic effect on ES cell-derived NPCs of glutamatergic neurons, but not on their progeny. This effect of VPA most likely occurred through the inhibition of HDACs, because similar phenotypes were observed following treatment with other HDAC inhibitors (HDACis) such as trichostatin A and sodium butyrate. The proapoptotic phenotype was not observed when cells were exposed to a structural analog of VPA, valpromide (VPM), which has the same antiepileptic effect as VPA, but does not inhibit HDACs. Western blotting confirmed that treatment with HDACis, but not VPM, significantly increased the levels of histone H3 acetylation in NPCs. HDACi treatments did not affect the survival of neurons, although the acetylation levels were increased to a limited extent. These results, which are based on a homogeneous culture system, suggest that VPA inhibits HDAC activity and induces the apoptosis of NPCs that are fated to differentiate into glutamatergic neurons. The dose-dependent effects of VPA both on apoptosis and hyperacetylation of histone H3 in NPCs supported this notion. These cell type- and differentiation stage-specific effects of VPA imply that dysfunction of HDACs during pregnancy significantly increase the risk of congenital malformations associated with VPA administration. PMID:23788034

  10. Bio-derived poly(gamma-glutamic acid) nanogels as controlled anticancer drug delivery carriers.

    PubMed

    Bae, Hee Ho; Cho, Mi Young; Hong, Ji Hyeon; Poo, Haryoung; Sung, Moon-Hee; Lim, Yong Taik

    2012-12-01

    We have developed a novel type of polymer nanogel loaded with anticancer drug based on bio-derived poly(gamma- glutamic acid) (gamma-PGA). gamma-PGA is a highly anionic polymer that is synthesized naturally by microbial species, most prominently in various bacilli, and has been shown to have excellent biocompatibility. Thiolated gamma-PGA was synthesized by covalent coupling between the carboxyl groups of gamma-PGA and the primary amine group of cysteamine. Doxorubicin (Dox)-loaded gamma-PGA nanogels were fabricated using the following steps: (1) an ionic nanocomplex was formed between thiolated gamma-PGA as the negative charge component, and Dox as the positive charge component; (2) addition of poly(ethylene glycol) (PEG) induced hydrogen-bond interactions between thiol groups of thiolated gamma-PGA and hydroxyl groups of PEG, resulting in the nanocomplex; and (3) disulfide crosslinked gamma-PGA nanogels were fabricated by ultrasonication. The average size and surface charge of Dox-loaded disulfide cross-linked gamma-PGA nanogels in aqueous solution were 136.3 +/- 37.6 nm and -32.5 +/- 5.3 mV, respectively. The loading amount of Dox was approximately 38.7 microgram per mg of gamma-PGA nanogel. The Dox-loaded disulfide cross-linked gamma-PGA nanogels showed controlled drug release behavior in the presence of reducing agents, glutathione (GSH) (1- 10 mM). Through fluorescence microscopy and FACS, the cellular uptake of gamma-PGA nanogels into breast cancer cells (MCF-7) was analyzed. The cytotoxic effect was evaluated using the MTT assay and was determined to be dependent on both the concentration and treatment time of gamma-PGA nanogels. The bio-derived gamma-PGA nanogels are expected to be a well-designed delivery carrier for controlled drug delivery applications. PMID:23221543

  11. Human GAPDH Is a Target of Aspirin’s Primary Metabolite Salicylic Acid and Its Derivatives

    PubMed Central

    Manohar, Murli; Harraz, Maged M.; Park, Sang-Wook; Schroeder, Frank C.; Snyder, Solomon H.; Klessig, Daniel F.

    2015-01-01

    The plant hormone salicylic acid (SA) controls several physiological processes and is a key regulator of multiple levels of plant immunity. To decipher the mechanisms through which SA’s multiple physiological effects are mediated, particularly in immunity, two high-throughput screens were developed to identify SA-binding proteins (SABPs). Glyceraldehyde 3-Phosphate Dehydrogenase (GAPDH) from plants (Arabidopsis thaliana) was identified in these screens. Similar screens and subsequent analyses using SA analogs, in conjunction with either a photoaffinity labeling technique or surface plasmon resonance-based technology, established that human GAPDH (HsGAPDH) also binds SA. In addition to its central role in glycolysis, HsGAPDH participates in several pathological processes, including viral replication and neuronal cell death. The anti-Parkinson’s drug deprenyl has been shown to suppress nuclear translocation of HsGAPDH, an early step in cell death and the resulting cell death induced by the DNA alkylating agent N-methyl-N’-nitro-N-nitrosoguanidine. Here, we demonstrate that SA, which is the primary metabolite of aspirin (acetyl SA) and is likely responsible for many of its pharmacological effects, also suppresses nuclear translocation of HsGAPDH and cell death. Analysis of two synthetic SA derivatives and two classes of compounds from the Chinese medicinal herb Glycyrrhiza foetida (licorice), glycyrrhizin and the SA-derivatives amorfrutins, revealed that they not only appear to bind HsGAPDH more tightly than SA, but also exhibit a greater ability to suppress translocation of HsGAPDH to the nucleus and cell death. PMID:26606248

  12. Human GAPDH Is a Target of Aspirin's Primary Metabolite Salicylic Acid and Its Derivatives.

    PubMed

    Choi, Hyong Woo; Tian, Miaoying; Manohar, Murli; Harraz, Maged M; Park, Sang-Wook; Schroeder, Frank C; Snyder, Solomon H; Klessig, Daniel F

    2015-01-01

    The plant hormone salicylic acid (SA) controls several physiological processes and is a key regulator of multiple levels of plant immunity. To decipher the mechanisms through which SA's multiple physiological effects are mediated, particularly in immunity, two high-throughput screens were developed to identify SA-binding proteins (SABPs). Glyceraldehyde 3-Phosphate Dehydrogenase (GAPDH) from plants (Arabidopsis thaliana) was identified in these screens. Similar screens and subsequent analyses using SA analogs, in conjunction with either a photoaffinity labeling technique or surface plasmon resonance-based technology, established that human GAPDH (HsGAPDH) also binds SA. In addition to its central role in glycolysis, HsGAPDH participates in several pathological processes, including viral replication and neuronal cell death. The anti-Parkinson's drug deprenyl has been shown to suppress nuclear translocation of HsGAPDH, an early step in cell death and the resulting cell death induced by the DNA alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine. Here, we demonstrate that SA, which is the primary metabolite of aspirin (acetyl SA) and is likely responsible for many of its pharmacological effects, also suppresses nuclear translocation of HsGAPDH and cell death. Analysis of two synthetic SA derivatives and two classes of compounds from the Chinese medicinal herb Glycyrrhiza foetida (licorice), glycyrrhizin and the SA-derivatives amorfrutins, revealed that they not only appear to bind HsGAPDH more tightly than SA, but also exhibit a greater ability to suppress translocation of HsGAPDH to the nucleus and cell death. PMID:26606248

  13. Evaluation of the toxicity data for peracetic acid in deriving occupational exposure limits: a minireview.

    PubMed

    Pechacek, Nathan; Osorio, Magdalena; Caudill, Jeff; Peterson, Bridget

    2015-02-17

    Peracetic acid (PAA) is a peroxide-based chemistry that is highly reactive and can produce strong local effects upon direct contact with the eyes, skin and respiratory tract. Given its increasing prominence in industry, attention has focused on health hazards and associated risks for PAA in the workplace. Occupational exposure limits (OEL) are one means to mitigate risks associated with chemical hazards in the workplace. A mini-review of the toxicity data for PAA was conducted in order to determine if the data were sufficient to derive health-based OELs. The available data for PAA frequently come from unpublished studies that lack sufficient study details, suffer from gaps in available information and often follow unconventional testing methodology. Despite these limitations, animal and human data suggest sensory irritation as the most sensitive endpoint associated with inhalation of PAA. Rodent RD50 data (the concentration estimated to cause a 50% depression in respiratory rate) were selected as the critical studies in deriving OELs. Based on these data, a range of 0.36-0.51mg/m(3) (0.1-0.2ppm) was calculated for a time-weighted average (TWA), and 1.2-1.7mg/m(3) (0.4-0.5ppm) as a range for a short-term exposure limit (STEL). These ranges compare favorably to other published OELs for PAA. Considering the applicable health hazards for this chemistry, a joint TWA/STEL OEL approach for PAA is deemed the most appropriate in assessing workplace exposures to PAA, and the selection of specific values within these proposed ranges represents a risk management decision. PMID:25542141

  14. A mushroom-derived amino acid, ergothioneine, is a potential inhibitor of inflammation-related DNA halogenation.

    PubMed

    Asahi, Takashi; Wu, Xiaohong; Shimoda, Hiroshi; Hisaka, Shinsuke; Harada, Etsuko; Kanno, Tomomi; Nakamura, Yoshimasa; Kato, Yoji; Osawa, Toshihiko

    2016-01-01

    Myeloperoxidase (MPO)-generated halogenating molecules, such as hypochlorous acid and hypobromous acid (HOBr), in inflammatory regions are postulated to contribute to disease progression. In this study, we showed that ergothioneine (EGT), derived from an edible mushroom, inhibited MPO activity as well as the formation of 8-bromo-2'-deoxyguanosine in vitro. The HOBr scavenging effect of EGT is higher than those of ascorbic acid and glutathione. We initially observed that the administration of Coprinus comatus, an edible mushroom containing a high amount of EGT, inhibited the UV-B-induced inflammatory responses and DNA halogenation, suggesting that EGT is a promising anti-inflammatory agent from mushrooms.

  15. An organic solvent-tolerant phenolic acid decarboxylase from Bacillus licheniformis for the efficient bioconversion of hydroxycinnamic acids to vinyl phenol derivatives.

    PubMed

    Hu, Hongfei; Li, Lulu; Ding, Shaojun

    2015-06-01

    A new phenolic acid decarboxylase gene (blpad) from Bacillus licheniformis was cloned and overexpressed in Escherichia coli. The full-length blpad encodes a 166-amino acid polypeptide with a predicted molecular mass and pI of 19,521 Da and 5.02, respectively. The recombinant BLPAD displayed maximum activity at 37 °C and pH 6.0. This enzyme possesses a broad substrate specificity and is able to decarboxylate p-coumaric, ferulic, caffeic, and sinapic acids at the relative ratios of specific activities 100:74.59:34.41:0.29. Kinetic constant K m values toward p-coumaric, ferulic, caffeic, and sinapic acids were 1.64, 1.55, 1.93, and 2.45 mM, and V max values were 268.43, 216.80, 119.07, and 0.78 U mg(-1), respectively. In comparison with other phenolic acid decarboxylases, BLPAD exhibited remarkable organic solvent tolerance and good thermal stability. BLPAD showed excellent catalytic performance in biphasic organic/aqueous systems and efficiently converted p-coumaric and ferulic acids into 4-vinylphenol and 4-vinylguaiacol. At 500 mM of p-coumaric and ferulic acids, the recombinant BLPAD produced a total 60.63 g l(-1) 4-vinylphenol and 58.30 g l(-1) 4-vinylguaiacol with the conversion yields 97.02 and 70.96 %, respectively. The low yield and product concentration are the crucial drawbacks to the practical bioproduction of vinyl phenol derivatives using phenolic acid decarboxylases. These unusual properties make BLPAD a desirable biocatalyst for commercial use in the bioconversion of hydroxycinnamic acids to vinyl phenol derivatives via enzymatic decarboxylation in a biphasic organic/aqueous reaction system. PMID:25547838

  16. Lewis base activation of Lewis acids: catalytic, enantioselective addition of glycolate-derived silyl ketene acetals to aldehydes.

    PubMed

    Denmark, Scott E; Chung, Won-Jin

    2008-06-20

    A catalytic system involving silicon tetrachloride and a chiral, Lewis basic bisphosphoramide catalyst is effective for the addition of glycolate-derived silyl ketene acetals to aldehydes. It was found that the sense of diastereoselectivity could be modulated by changing the size of the substituents on the silyl ketene acetals. In general, the trimethylsilyl ketene acetals derived from methyl glycolates with a large protecting group on the alpha-oxygen provide enantiomerically enriched alpha,beta-dihydroxy esters with high syn-diastereoselectivity, whereas the tert-butyldimethylsilyl ketene acetals derived from bulky esters of alpha-methoxyacetic acid provide enantiomerically enriched alpha,beta-dihydroxy esters with high anti-diastereoselecitvity.

  17. Synthesis and biological activity of ester derivatives of mycophenolic acid and acridines/acridones as potential immunosuppressive agents.

    PubMed

    Cholewinski, Grzegorz; Iwaszkiewicz-Grzes, Dorota; Trzonkowski, Piotr; Dzierzbicka, Krystyna

    2016-12-01

    Improved derivatives of mycophenolic acid (MPA) are necessary to reduce the frequency of adverse effects, this drug exerts in treated patients. In this study, MPA was coupled with N-(ω-hydroxyalkyl)-9-acridone-4-carboxamides or N-(ω-hydroxyalkyl)acridine-4-carboxamides to give respective ester conjugates upon Yamaguchi protocol. This esterification required protection of phenol group in MPA. Designed conjugates revealed higher potency in vitro than parent MPA. Acridine derivatives were more active than acridone analogs and length of the alkyl linker between MPA and heterocyclic units influenced the observed cytotoxicity. Derivatives 2b, 2d, 3a, 3b displayed the most promising immunosuppressive activity.

  18. Cytotoxicity of copper(II)-complexes with some S-alkyl derivatives of thiosalicylic acid. Crystal structure of the binuclear copper(II)-complex with S-ethyl derivative of thiosalicylic acid

    NASA Astrophysics Data System (ADS)

    Nikolić, Miloš V.; Mijajlović, Marina Ž.; Jevtić, Verica V.; Ratković, Zoran R.; Novaković, Slađana B.; Bogdanović, Goran A.; Milovanović, Jelena; Arsenijević, Aleksandar; Stojanović, Bojana; Trifunović, Srećko R.; Radić, Gordana P.

    2016-07-01

    The spectroscopically predicted structure of the obtained copper(II)-complex with S-ethyl derivative of thiosalicylic acid was confirmed by X-ray structural study and compared to previously reported crystal structure of the Cu complex with S-methyl derivative. Single crystals suitable for X-ray measurements were obtained by slow crystallization from a water solution. Cytotoxic effects of S-alkyl (R = benzyl (L1), methyl (L2), ethyl (L3), propyl (L4) and butyl (L5)) derivatives of thiosalicylic acid and the corresponding binuclear copper(II)-complexes on murine colon carcinoma cell lines, CT26 and CT26.CL25 and human colon carcinoma cell line HCT-116 were reported here. The analysis of cancer cell viability showed that all the tested complexes had low cytotoxic effect on murine colon carcinoma cell lines, but several times higher cytotoxicity on normal human colon carcinoma cells.

  19. Structure, stability, and antiplatelet activity of O-acyl derivatives of salicylic acid and lipophilic esters of acetylsalicylate.

    PubMed

    Zavodnik, Ilya B; Lapshina, Elena; Sudnikovich, Elena; Boncler, Magdalena; Luzak, Bogusława; Rózalski, Marcin; Helińska, Magdalena; Watała, Cezary

    2009-01-01

    The anti-thrombotic activity of acetylsalicylic acid (ASA) has been shown to be due to specific irreversible acetylation of blood platelet cyclooxygenase. The aim of our study was to investigate the associations between the antiplatelet activities of derivatives of both ASA and salicylic acid (SA), as well as the structure, stability, and molecular properties of these compounds. Homologous series of O-acyl derivatives of salicylic acid (propionyl-, butyrylsalicylic acids, PSA, BSA) and lipophilic dodecyl (C12)-, hexadecyl (C16)-, and cholesteryl acetylsalicylates were synthesized and tested for structure-activity relationships. The molecular properties (heat of formation, molecular surface area, dipole moment) of ASA and SA derivatives obtained by theoretical calculations changed with the increasing length of the acyl or alkyl residue. The inhibition of whole blood platelet aggregation and the reduction in thromboxane (TX) generation by O-acyl derivatives were concentration-dependent and decreased along with increasing the length of acyl hain. These effects correlated with the extent of platelet reactivity and P-selectin expression inhibition in collagen-activated platelets. In contrast to ASA and O-acyl derivatives of SA, none of the lipophilic ASA derivatives had a significant inhibitory effect on platelet aggregation. In conclusion, all SA and ASA derivatives studied under in vitro conditions showed much lower antiplatelet activities than ASA itself, despite their higher affinity to plasma proteins or membrane components and their equivalent ability to acetylate protein free amino groups.We suggest the significance of the carboxylic group, dipole moment, geometry, and size of these pharmaceuticals in their ability to bind to the active site of cyclooxygenase and their antiplatelet efficacy.

  20. Oligonucleoside alkyl or arylphosphonate derivatives capable of crosslinking with or cleaving nucleic acids

    DOEpatents

    Miller, P.S.; Ts'o, P.O.P.

    1999-06-15

    A composition for inactivating a target nucleic acid which comprises an oligonucleoside alkyl or arylphosphonate analogue which is complementary to the sequence of the target nucleic acid is provided. It includes a functional group which reacts with the target nucleic acid to render the target nucleic acid inactive or nonfunctional. 16 figs.

  1. Oligonucleoside alkyl or arylphosphonate derivatives capable of crosslinking with or cleaving nucleic acids

    DOEpatents

    Miller, Paul S.; Ts'o, Paul O.P.

    1999-06-15

    A composition for inactivating a target nucleic acid which comprises an oligonucleoside alkyl or arylphosphonate analogue which is complementary to the sequence of the target nucleic acid and includes a functional group which reacts with the target nucleic acid to render the target nucleic acid inactive or nonfunctional.

  2. Development of a bioprocess to convert PET derived terephthalic acid and biodiesel derived glycerol to medium chain length polyhydroxyalkanoate.

    PubMed

    Kenny, Shane T; Runic, Jasmina Nikodinovic; Kaminsky, Walter; Woods, Trevor; Babu, Ramesh P; O'Connor, Kevin E

    2012-08-01

    Sodium terephthalate (TA) produced from a PET pyrolysis product and waste glycerol (WG) from biodiesel manufacture were supplied to Pseudomonas putida GO16 in a fed-batch bioreactor. Six feeding strategies were employed by altering the sequence of TA and WG feeding. P. putida GO16 reached 8.70 g/l cell dry weight (CDW) and 2.61 g/l PHA in 48 h when grown on TA alone. When TA and WG were supplied in combination, biomass productivity (g/l/h) was increased between 1.3- and 1.7-fold and PHA productivity (g/l/h) was increased 1.8- to 2.2-fold compared to TA supplied alone. The monomer composition of the PHA accumulated from TA or WG was predominantly composed of 3-hydroxydecanoic acid. PHA monomers 3-hydroxytetradeeanoic acid and 3-hydroxytetradecenoic acid were not present in PHA accumulated from TA alone but were present when WG was supplied to the fermentation. When WG was either the sole carbon source or the predominant carbon source supplied to the fermentation the molecular weight of PHA accumulated was lower compared to PHA accumulated when TA was supplied as the sole substrate. Despite similarities in data for the properties of the polymers, PHAs produced with WG present in the PHA accumulation phase were tacky while PHA produced where TA was the sole carbon substrate in the polymer accumulation phase exhibited little or no tackiness at room temperature. The co-feeding of WG to fermentations allows for increased utilisation of TA. The order of feeding of WG and TA has an effect on TA utilisation and polymer properties. PMID:22581066

  3. Development of a bioprocess to convert PET derived terephthalic acid and biodiesel derived glycerol to medium chain length polyhydroxyalkanoate.

    PubMed

    Kenny, Shane T; Runic, Jasmina Nikodinovic; Kaminsky, Walter; Woods, Trevor; Babu, Ramesh P; O'Connor, Kevin E

    2012-08-01

    Sodium terephthalate (TA) produced from a PET pyrolysis product and waste glycerol (WG) from biodiesel manufacture were supplied to Pseudomonas putida GO16 in a fed-batch bioreactor. Six feeding strategies were employed by altering the sequence of TA and WG feeding. P. putida GO16 reached 8.70 g/l cell dry weight (CDW) and 2.61 g/l PHA in 48 h when grown on TA alone. When TA and WG were supplied in combination, biomass productivity (g/l/h) was increased between 1.3- and 1.7-fold and PHA productivity (g/l/h) was increased 1.8- to 2.2-fold compared to TA supplied alone. The monomer composition of the PHA accumulated from TA or WG was predominantly composed of 3-hydroxydecanoic acid. PHA monomers 3-hydroxytetradeeanoic acid and 3-hydroxytetradecenoic acid were not present in PHA accumulated from TA alone but were present when WG was supplied to the fermentation. When WG was either the sole carbon source or the predominant carbon source supplied to the fermentation the molecular weight of PHA accumulated was lower compared to PHA accumulated when TA was supplied as the sole substrate. Despite similarities in data for the properties of the polymers, PHAs produced with WG present in the PHA accumulation phase were tacky while PHA produced where TA was the sole carbon substrate in the polymer accumulation phase exhibited little or no tackiness at room temperature. The co-feeding of WG to fermentations allows for increased utilisation of TA. The order of feeding of WG and TA has an effect on TA utilisation and polymer properties.

  4. Multiple Targets of Salicylic Acid and Its Derivatives in Plants and Animals

    PubMed Central

    Klessig, Daniel F.; Tian, Miaoying; Choi, Hyong Woo

    2016-01-01

    Salicylic acid (SA) is a critical plant hormone that is involved in many processes, including seed germination, root initiation, stomatal closure, floral induction, thermogenesis, and response to abiotic and biotic stresses. Its central role in plant immunity, although extensively studied, is still only partially understood. Classical biochemical approaches and, more recently, genome-wide high-throughput screens have identified more than two dozen plant SA-binding proteins (SABPs), as well as multiple candidates that have yet to be characterized. Some of these proteins bind SA with high affinity, while the affinity of others exhibit is low. Given that SA levels vary greatly even within a particular plant species depending on subcellular location, tissue type, developmental stage, and with respect to both time and location after an environmental stimulus such as infection, the presence of SABPs exhibiting a wide range of affinities for SA may provide great flexibility and multiple mechanisms through which SA can act. SA and its derivatives, both natural and synthetic, also have multiple targets in animals/humans. Interestingly, many of these proteins, like their plant counterparts, are associated with immunity or disease development. Two recently identified SABPs, high mobility group box protein and glyceraldehyde 3-phosphate dehydrogenase, are critical proteins that not only serve key structural or metabolic functions but also play prominent roles in disease responses in both kingdoms. PMID:27303403

  5. Crystal structure of a lithium salt of a glucosyl derivative of lithocholic acid.

    PubMed

    Gubitosi, Marta; Meijide, Francisco; D'Annibale, Andrea; Vázquez Tato, José; Jover, Aida; Galantini, Luciano; Travaglini, Leana; di Gregorio, Maria Chiara; Pavel, Nicolae V

    2016-09-01

    The crystal structure of a Li(+) salt of a glucosyl derivative of lithocholic acid (lithium 3α-(α-d-glucopyranosyl)-5β-cholan-24-oate) has been solved. The crystal belongs to the orthorhombic system, P212121 spatial group, and includes acetone and water in the structure with a 1:1:2 stoichiometry. Monolayers, having a hydrophobic interior and hydrophilic edges, are recognized in the crystal structure. Li(+) is coordinated to three hydroxyl groups of three different glucose residues, with two of them belonging to the same monolayer. A fourth molecule, located in this monolayer, is involved in the coordination of the cation through the carboxylate ion by an electrostatic interaction, thus completing a distorted tetrahedron. All Li(+)-oxygen distances values are very close to the sum of the ionic radius of Li(+) and van der Waals radius of oxygen. Each steroid molecule is linked to other five steroid molecules through hydrogen bonds. Water and acetone are also involved in the hydrogen bond network. A hierarchical organization can be recognized in the crystal, the helical assembly along 21 screw axes being left-handed. PMID:27394960

  6. Dynamic Covalent Chemistry-based Sensing: Pyrenyl Derivatives of Phenylboronic Acid for Saccharide and Formaldehyde

    NASA Astrophysics Data System (ADS)

    Chang, Xingmao; Fan, Jiayun; Wang, Min; Wang, Zhaolong; Peng, Haonan; He, Gang; Fang, Yu

    2016-08-01

    We synthesized two specially designed pyrenyl (Py) derivatives of phenylboronic acid, PSNB1 and PSNB2, of which PSNB2 self-assemble to form dynamic aggregate in methanol-water mixture (1:99, v/v) via intermolecular H-bonding and pi-pi stacking. Interestingly, the dynamic aggregate shows smart response to presence of fructose (F) as evidenced by fluorescence color change from green to blue. More interestingly, the fluorescence emission of the resulted PSNB2-F changes from blue to green with the addition of formaldehyde (FA). The reason behind is formation of a PSNB2-F dimer via FA cross-linking. Based upon the reactions as found, sensitive and fast sensing of F and FA in water was realized, of which the experimental DLs could be significantly lower than 10 μM for both analytes, and the response times are less than 1 min. It is believed that not only the materials as created may have the potential to find real-life applications but also the strategy as developed can be adopted to develop other dynamic materials.

  7. Dynamic Covalent Chemistry-based Sensing: Pyrenyl Derivatives of Phenylboronic Acid for Saccharide and Formaldehyde

    PubMed Central

    Chang, Xingmao; Fan, Jiayun; Wang, Min; Wang, Zhaolong; Peng, Haonan; He, Gang; Fang, Yu

    2016-01-01

    We synthesized two specially designed pyrenyl (Py) derivatives of phenylboronic acid, PSNB1 and PSNB2, of which PSNB2 self-assemble to form dynamic aggregate in methanol-water mixture (1:99, v/v) via intermolecular H-bonding and pi-pi stacking. Interestingly, the dynamic aggregate shows smart response to presence of fructose (F) as evidenced by fluorescence color change from green to blue. More interestingly, the fluorescence emission of the resulted PSNB2-F changes from blue to green with the addition of formaldehyde (FA). The reason behind is formation of a PSNB2-F dimer via FA cross-linking. Based upon the reactions as found, sensitive and fast sensing of F and FA in water was realized, of which the experimental DLs could be significantly lower than 10 μM for both analytes, and the response times are less than 1 min. It is believed that not only the materials as created may have the potential to find real-life applications but also the strategy as developed can be adopted to develop other dynamic materials. PMID:27498703

  8. Curcumin Derivatives as Green Corrosion Inhibitors for α-Brass in Nitric Acid Solution

    NASA Astrophysics Data System (ADS)

    Fouda, A. S.; Elattar, K. M.

    2012-11-01

    1,7- Bis-(4-hydroxy-3-methoxy-phenyl)-hepta-1,6-diene-4-arylazo-3,5-dione I-V have been investigated as corrosion inhibitors for α-brass in 2 M nitric acid solution using weight-loss and galvanostatic polarization techniques. The efficiency of the inhibitors increases with the increase in the inhibitor concentration but decreases with a rise in temperature. The conjoint effect of the curcumin derivatives and KSCN has also been studied. The apparent activation energy ( E a*) and other thermodynamic parameters for the corrosion process have also been calculated. The galvanostatic polarization data indicated that the inhibitors were of mixed-type, but the cathode is more polarized than the anode. The slopes of the cathodic and anodic Tafel lines ( b c and b a) are maintained approximately equal for various inhibitor concentrations. However, the value of the Tafel slopes increases together as inhibitor concentration increases. The adsorption of these compounds on α-brass surface has been found to obey the Frumkin's adsorption isotherm. The mechanism of inhibition was discussed in the light of the chemical structure of the undertaken inhibitors.

  9. Action of some bisquaternary derivatives of phthalic acids and related substances on neuromuscular transmission

    PubMed Central

    Danilov, A. F.; Kvitko, I. J.; Lavrentieva, V. V.; Michelson, M. J.; Porai-Koshits, B. A.; Rozhkova, E. K.; Shelkovnikov, S. A.

    1972-01-01

    1. All the bisquaternary derivatives of terephthalic acid with three methyl groups on each nitrogen atom (PK-107, PK-95, PK-97 and PK-126) were depolarizing neuromuscular blocking agents. The most active was the compound PK-97, in which the two quaternary groups are separated by sixteen atoms and are about 20 Å (2 nm) apart. Activity was reduced many fold either by decreasing the separation to twelve atoms or by increasing it to eighteen atoms. It was also reduced several hundred fold when one trimethylammonium group in PK-97 was replaced by a hydrogen atom (as in PK-119). 2. The presence and position of the ester groups in these compounds is important; depolarizing activity is in most cases greatest when the ester groups are the same distance from the quaternary nitrogen atoms as in acetylcholine, that is, in carbolonium, sebacoyldicholine and PK-154. The monoquaternary analogues of carbolonium and sebacoyldicholine are appreciably active, having between about one-tenth to one-fifth of the activity of their bisquaternary analogues. 3. The relationships between the structure and activity of these compounds are discussed, particular consideration being given to the structure of the chain separating the quaternary groups and the arrangement of acetylcholine receptors on cells and of esterbinding groups within these receptors. PMID:4339387

  10. Biological Significance of Urolithins, the Gut Microbial Ellagic Acid-Derived Metabolites: The Evidence So Far

    PubMed Central

    Espín, Juan Carlos; Larrosa, Mar; García-Conesa, María Teresa; Tomás-Barberán, Francisco

    2013-01-01

    The health benefits attributed to pomegranate have been associated with its high content in polyphenols, particularly ellagitannins. This is also the case for other ellagitannin-containing fruits and nuts including strawberry, raspberry, blackberry, walnuts, and muscadine grapes. The bioavailability of ellagitannins and ellagic acid is however very low. These molecules suffer extensive metabolism by the gut microbiota to produce urolithins that are much better absorbed. Urolithins circulate in plasma as glucuronide and sulfate conjugates at concentrations in the range of 0.2–20 μM. It is therefore conceivable that the health effects of ellagitannin-containing products can be associated with these gut-produced urolithins, and thus the evaluation of the biological effects of these metabolites is essential. Recent research, mostly based on in vitro testing, has shown preliminary evidence of the anti-inflammatory, anticarcinogenic, antiglycative, antioxidant, and antimicrobial effects of urolithins, supporting their potential contribution to the health effects attributed to pomegranate and ellagitannin-rich foods. The number of in vivo studies is still limited, but they show preventive effects of urolithins on gut and systemic inflammation that encourage further research. Both in vivo and mechanistic studies are necessary to clarify the health effects of these metabolites. Attention should be paid when designing these mechanistic studies in order to use the physiologically relevant metabolites (urolithins in gut models and their conjugated derivatives in systemic models) at concentrations that can be reached in vivo. PMID:23781257

  11. Biological significance of urolithins, the gut microbial ellagic Acid-derived metabolites: the evidence so far.

    PubMed

    Espín, Juan Carlos; Larrosa, Mar; García-Conesa, María Teresa; Tomás-Barberán, Francisco

    2013-01-01

    The health benefits attributed to pomegranate have been associated with its high content in polyphenols, particularly ellagitannins. This is also the case for other ellagitannin-containing fruits and nuts including strawberry, raspberry, blackberry, walnuts, and muscadine grapes. The bioavailability of ellagitannins and ellagic acid is however very low. These molecules suffer extensive metabolism by the gut microbiota to produce urolithins that are much better absorbed. Urolithins circulate in plasma as glucuronide and sulfate conjugates at concentrations in the range of 0.2-20  μ M. It is therefore conceivable that the health effects of ellagitannin-containing products can be associated with these gut-produced urolithins, and thus the evaluation of the biological effects of these metabolites is essential. Recent research, mostly based on in vitro testing, has shown preliminary evidence of the anti-inflammatory, anticarcinogenic, antiglycative, antioxidant, and antimicrobial effects of urolithins, supporting their potential contribution to the health effects attributed to pomegranate and ellagitannin-rich foods. The number of in vivo studies is still limited, but they show preventive effects of urolithins on gut and systemic inflammation that encourage further research. Both in vivo and mechanistic studies are necessary to clarify the health effects of these metabolites. Attention should be paid when designing these mechanistic studies in order to use the physiologically relevant metabolites (urolithins in gut models and their conjugated derivatives in systemic models) at concentrations that can be reached in vivo.

  12. Anti-biofilm activity of ultrashort cinnamic acid peptide derivatives against medical device-related pathogens.

    PubMed

    Laverty, Garry; McCloskey, Alice P; Gorman, Sean P; Gilmore, Brendan F

    2015-10-01

    The threat of antimicrobial resistance has placed increasing emphasis on the development of innovative approaches to eradicate multidrug-resistant pathogens. Biofilm-forming microorganisms, for example, Staphylococcus epidermidis and Staphylococcus aureus, are responsible for increased incidence of biomaterial infection, extended hospital stays and patient morbidity and mortality. This paper highlights the potential of ultrashort tetra-peptide conjugated to hydrophobic cinnamic acid derivatives. These peptidomimetic molecules demonstrate selective and highly potent activity against resistant biofilm forms of Gram-positive medical device-related pathogens. 3-(4-Hydroxyphenyl)propionic)-Orn-Orn-Trp-Trp-NH2 displays particular promise with minimum biofilm eradication concentration (MBEC) values of 125 µg/ml against methicillin sensitive (ATCC 29213) and resistant (ATCC 43300) S. aureus and activity shown against biofilm forms of Escherichia coli (MBEC: 1000 µg/ml). Kill kinetics confirms complete eradication of established 24-h biofilms at MBEC with 6-h exposure. Reduced cell cytotoxicity, relative to Gram-positive pathogens, was proven via tissue culture (HaCaT) and haemolysis assays (equine erythrocytes). Existing in nature as part of the immune response, antimicrobial peptides display great promise for exploitation by the pharmaceutical industry in order to increase the library of available therapeutic molecules. Ultrashort variants are particularly promising for translation as clinical therapeutics as they are more cost-effective, easier to synthesise and can be tailored to specific functional requirements based on the primary sequence allowing factors such as spectrum of activity to be varied.

  13. Dynamic Covalent Chemistry-based Sensing: Pyrenyl Derivatives of Phenylboronic Acid for Saccharide and Formaldehyde.

    PubMed

    Chang, Xingmao; Fan, Jiayun; Wang, Min; Wang, Zhaolong; Peng, Haonan; He, Gang; Fang, Yu

    2016-01-01

    We synthesized two specially designed pyrenyl (Py) derivatives of phenylboronic acid, PSNB1 and PSNB2, of which PSNB2 self-assemble to form dynamic aggregate in methanol-water mixture (1:99, v/v) via intermolecular H-bonding and pi-pi stacking. Interestingly, the dynamic aggregate shows smart response to presence of fructose (F) as evidenced by fluorescence color change from green to blue. More interestingly, the fluorescence emission of the resulted PSNB2-F changes from blue to green with the addition of formaldehyde (FA). The reason behind is formation of a PSNB2-F dimer via FA cross-linking. Based upon the reactions as found, sensitive and fast sensing of F and FA in water was realized, of which the experimental DLs could be significantly lower than 10 μM for both analytes, and the response times are less than 1 min. It is believed that not only the materials as created may have the potential to find real-life applications but also the strategy as developed can be adopted to develop other dynamic materials. PMID:27498703

  14. Synthesis and in vitro biocompatibility assessment of a poly(amic acid) derived from ethylenediaminetetraacetic dianhydride.

    PubMed

    Padavan, Donna T; Hamilton, Amanda M; Boughner, Derek R; Wan, Wankei

    2011-01-01

    Poly(amic acid) (PAA) derived from ethylenediaminetetracetic dianhydride shows great potential as a biomaterial suitable for biomedical applications. To evaluate this polymer class further, in vitro cell toxicity (WST-1/ECS, ELISA based) and cell compatibility (cell adhesion and cell proliferation) tests were conducted to establish structure-toxicity relationships. PAAs with a number-average molecular weight ranging between 100 to 200 kg/mol were synthesized at 37°C after 24 h. Porcine radial artery cells (RACs) and descending aorta endothelial cells (ECs) were seeded independently in a 96-well cell culture plate at a cell density of 5000 cells/cm(2) to observe toxic effects. Similarly, RACs and ECs were seeded independently onto PAA coated and uncoated cover slips at a cell density of 7000 cells/cm(2) to observe growth patterns. Our results showed no toxicity after 96 h of incubation and in addition, both RACs and ECs adhered and proliferated on the PAA films, preserving their phenotype during this time. The tested synthetic material seems promising as a future biomaterial and should elicit a desired cellular response upon implantation.

  15. Synthesis and Performance Properties of Cationic Fabric Softeners Derived from Free Fatty Acid of Tallow Fat.

    PubMed

    Mondal, Mithun G; Pratap, Amit Prabhakar

    2016-08-01

    Esterquat cationic softener is basically the class of surface active quaternary ammonium compounds. Esterquat compounds were synthesized and their surface behavior, antibacterial activity and Textile softening properties were investigated. Easily found cheap material was used to synthesize cationic fabric softeners. This fabric softener will be a good for commercially and industrially important because their emulsify activity, rewettability dispersing power and softness. Free fatty acids were derived from tallow oil and were treated with triethanolamine and mono-ethanolamine at 140°C. This diester was quaternaries with dimethyl sulphate and benzyl chloride. The synthesized esterquat compounds were characterized by its cationic content, 1H NMR and FT-IR analysis. In addition to the cationic content, surface tension, CMC (critical micelle concentration), rewettability, fabric softening, emulsification and dispersing power were determined as their surface-active properties. The fabric softening activity of esterquat and esteramide prepared from DMS was better softening activity of fabrics compared to untreated cotton and polyester fabrics cloth. The presented result shows that the esterquat made from BCl exhibit the best dispersing power. The esterquat made from DMS both in TEA and MEA shows good rewettability was determined. PMID:27430381

  16. [Antitoxic properties of pantothenic acid derivatives, precursors of coenzyme A biosynthesis, with regard to kanamycin].

    PubMed

    Moĭseenok, A G; Dorofeev, B F; Sheĭbak, V M; Khomich, T I

    1984-11-01

    The effect of calcium pantothenate (CPN)B 4'-phospho-CPN (PCP), pantetheine (PT) and calcium S-sulfopantetheine (SPN) on acute toxicity of kanamycin sulfate was studied on albino mice. The above derivatives of pantothenic acid except PT lowered the antibiotic toxicity. The coefficient of the antitoxic effect (LD50/ED50) of SPN and PCP was 1.3-1.4 times higher than that of CPN. The combined use of kanamycin (1/5 of the LD50) with CPN, PCP or PT (30 mg/kg bw was equivalent to CPN) for 15 days prevented the increase in the total content of CoA and in the content of the fraction of free CoA and the precursors of its biosynthesis participating in the reaction of N-acetylation in the liver and brain. The contents of these substances were within the normal during the whole experiment. A certain increase in the activity of pantothenate kinase in the liver cytosol due to the use of kanamycin was eliminated by the simultaneous use of PCP and PT. The vitamin-containing compounds PCP and SPN were recommended for the clinical trials as agents preventing complications of kanamycin therapy. PMID:6524887

  17. [Metabolism of pantothenic acid and its derivatives in animals deficient in this enzyme].

    PubMed

    Gurinovich, V A; Moiseenok, A G

    1987-01-01

    Distribution of [14C]labelled metabolites of pantothenic acid (PAA) has been studied in tissues of normal and PAA-deficient rats-weaners 6 h after single injection of the calcium pantothenate (PAA-Ca), calcium 4'-phosphopantothenate (PAA-Ca) or pantethine (PT) preparations. Essential differences in the intertissue distribution of vitamin derivatives to be injected are revealed against a background of a higher vitamin-retaining ability of the PAA-deficient tissues. A degree of radionuclides' biotransformation into CoA permits them to be arranged in the series: PPA-Ca greater than PAA-Ca greater than PT. In PAA-deficient animals which were injected labelled PPA-Ca up to 41% of the liver radioactivity is concentrated in the CoA fraction and the quantity of label in the composition of PAA-protein cytosolium complexes increases considerably. It is supposed that there is a special PAA-depositing system which provides the intracellular CoA biosynthesis. PMID:3686695

  18. Microbial conversion of synthetic and food waste-derived volatile fatty acids to lipids.

    PubMed

    Vajpeyi, Shashwat; Chandran, Kartik

    2015-01-01

    Lipid accumulation in the oleaginous yeast Cryptococcus albidus was evaluated using mixtures of volatile fatty acids (VFA) as substrates. In general, batch growth under nitrogen limitation led to higher lipid accumulation using synthetic VFA. During batch growth, an initial COD:N ratio of 25:1mg COD:mg N led to maximum intracellular lipid accumulation (28.3 ± 0.7% g/g dry cell weight), which is the maximum reported for C. albidus using VFA as the carbon source, without compromising growth kinetics. At this feed COD:N ratio, chemostat cultures fed with synthetic VFA yielded statistically similar intracellular lipid content as batch cultures (29.9 ± 1.9%, g/g). However, batch cultures fed with VFA produced from the fermentation of food waste, yielded a lower lipid content (14.9 ± 0.1%, g/g). The lipid composition obtained with synthetic and food-waste-derived VFA was similar to commercial biodiesel feedstock. We therefore demonstrate the feasibility of linking biochemical waste treatment and biofuel production using VFA as key intermediates.

  19. Anti-biofilm activity of ultrashort cinnamic acid peptide derivatives against medical device-related pathogens.

    PubMed

    Laverty, Garry; McCloskey, Alice P; Gorman, Sean P; Gilmore, Brendan F

    2015-10-01

    The threat of antimicrobial resistance has placed increasing emphasis on the development of innovative approaches to eradicate multidrug-resistant pathogens. Biofilm-forming microorganisms, for example, Staphylococcus epidermidis and Staphylococcus aureus, are responsible for increased incidence of biomaterial infection, extended hospital stays and patient morbidity and mortality. This paper highlights the potential of ultrashort tetra-peptide conjugated to hydrophobic cinnamic acid derivatives. These peptidomimetic molecules demonstrate selective and highly potent activity against resistant biofilm forms of Gram-positive medical device-related pathogens. 3-(4-Hydroxyphenyl)propionic)-Orn-Orn-Trp-Trp-NH2 displays particular promise with minimum biofilm eradication concentration (MBEC) values of 125 µg/ml against methicillin sensitive (ATCC 29213) and resistant (ATCC 43300) S. aureus and activity shown against biofilm forms of Escherichia coli (MBEC: 1000 µg/ml). Kill kinetics confirms complete eradication of established 24-h biofilms at MBEC with 6-h exposure. Reduced cell cytotoxicity, relative to Gram-positive pathogens, was proven via tissue culture (HaCaT) and haemolysis assays (equine erythrocytes). Existing in nature as part of the immune response, antimicrobial peptides display great promise for exploitation by the pharmaceutical industry in order to increase the library of available therapeutic molecules. Ultrashort variants are particularly promising for translation as clinical therapeutics as they are more cost-effective, easier to synthesise and can be tailored to specific functional requirements based on the primary sequence allowing factors such as spectrum of activity to be varied. PMID:26310860

  20. Identification of the monobrominated derivative of Acid Red 52 (Food Red No. 106) in pickled vegetables.

    PubMed

    Ochi, Naoki; Okuda, Tetsuya; Fujii, Hisashi

    2016-09-01

    Two unknown dyes (purple and purplish-red) were detected by TLC in two pickled vegetable (sakura-zuke daikon) samples containing Acid Red 52 (AR) and New Coccine as food colorants. HPLC with diode-array detection and LC/MS analyses suggested that the purple dye is monobrominated AR and the purplish-red dye is its N-desethyl derivative, which would be generated mainly during sample preparation. For the identification of the purple dye, a reference compound was prepared by bromination of AR followed by isolation of the monobrominated AR, the structure of which was elucidated as 4'-brominated AR (4'BrAR) by LC/ToF-MS and (1)H-NMR spectroscopy. The purple dye was confirmed as 4'BrAR by comparison of its retention time, ultraviolet-visible spectrum and mass spectrum with those of the prepared reference compound. To our knowledge, this is the first report of the detection of 4'BrAR in foods. PMID:27662432