- Coumaric acid derivatives as tyrosinase inhibitors: Efficacy studies through in silico, in vitro and ex vivo approaches
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p-Coumaric acid is a known inhibitor of tyrosinase, an enzyme involved in the initial steps of the melanin synthesis in human and other species. However, its low lipophilicity impairs its penetration through skin and efficacy as antimelanogenic agent indeed. Accordingly, this paper reports the assessment of several coumaric acid derivatives as tyrosinase inhibitors and antimelanogenic agents in in vitro, in silico and ex vivo assays. The compounds were designed with modifications in the aromatic and acid moieties of p-coumaric acid, being the coumarate esters the most promising derivatives. The compounds showed higher tyrosinase inhibitory activity (pIC50 3.7–4.2) than the parent acid, being compounds 1d, 1e and 1f the most potent inhibitors. Docking analysis showed that these esters are competitive inhibitors per se, and act independently of a redox mechanism as suggested by DPPH assays. Moreover, the esters showed efficacy in reducing the melanin deposition in human skin fragments at 0.1% concentration, especially compound 1e. In summary, there is an important equilibria between tyrosinase affinity and lipophilicity that must be considered to get effective antimelanogenic agents with adequate permeability in the skin.
- Fernandes, Jo?o Paulo S.,Ferrarini, Márcio,Mercaldi, Vitória Gallo,Nazato, Lucas Idacir Sbrugnera,Padovani, Giovana,Sufi, Bianca da Silva,Varela, Marina Themoteo
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- Alkyl and aryl derivatives based on p-coumaric acid modification and inhibitory action against leishmania braziliensis and plasmodium falciparum
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In low-income populations, neglected diseases are the principal cause of mortality. Of these, leishmaniasis and malaria, being parasitic, protozoan infections, affect millions of people worldwide and are creating a public health problem. The present work evaluates the leishmanicidal and antiplasmodial action of a series of twelve p-coumaric acid derivatives. Of the tested derivatives, eight presented antiparasitic activities 1-3, 8-12. The hexyl p-coumarate derivative (9) (4.14 ± 0.55 μg/mL; selectivity index (SI) = 2.72) showed the highest leishmanicidal potency against the Leishmania braziliensis amastigote form. The results of the molecular docking study suggest that this compound inhibits aldehyde dehydrogenase (ALDH), mitogen-activated kinase protein (MPK4), and DNA topoisomerase 2 (TOP2), all of which are key enzymes in the development of Leishmania braziliensis. The data indicate that these enzymes interact via Van derWaals bonds, hydrophobic interactions, and hydrogen bonds with phenolic and aliphatic parts of this same compound. Of the other compounds analyzed, methyl p-coumarate (64.59 ± 2.89 μg/mL; IS = 0.1) demonstrated bioactivity against Plasmodium falciparum. The study reveals that esters presenting a p-coumarate substructure are promising for use in synthesis of derivatives with good antiparasitic profiles.
- De Sousa, Dami?o P.,Lopes, Susiany P.,Pérez-Castillo, Yunierkis,Robledo, Sara M.,Yepe, Lina M.
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supporting information
(2020/08/24)
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- Antiallergic activity of rosmarinic acid esters is modulated by hydrophobicity, and bulkiness of alkyl side chain
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Methyl, propyl and hexyl esters of rosmarinic, caffeic and p-coumaric acids were tested for antiallergic activity, and rosmarinic acid propyl ester exhibited the greatest β-hexosaminidase release suppression (IC50, 23.7 μM). Quadratic correlations between pIC50 and cLogP (r2 = 0.94, 0.98, and 1.00, respectively) were observed in each acid ester series. The antiallergic activity is modulated by hydrophobicity, and alkyl chain bulkiness.
- Zhu, Fengxian,Xu, Zhongming,Yonekura, Lina,Yang, Ronghua,Tamura, Hirotoshi
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p. 1178 - 1182
(2015/10/05)
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- Synthesis and Study of Novel Mesogenic Homologous Series: 4-(4′- n -alkoxy benzoyloxy)- n -propyl Cinnamates
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A novel homologous series of liquid crystals viz. 4-(4′-n-alkoxy benzoyloxy) n-propyl cinnamates comprising of 11 homologues has been synthesized. It is a middle ordered melting type of series with exhibition of smectic and nematic mesophases. The first to fifth members of the series are non-mesomorphic. Mesomorphic behavior commences from the sixth homologue. The octyloxy (C8) and decyloxy (C10) homologues are polymesomorphic. The smectic-nematic and nematic-isotropic transition curves behave in a normal manner except for the hexadecyl derivative, which slightly deviates from normal behavior (N-I). An odd-even effect was not observed for the N-I or Sm-N transition curves. The texture of nematic phase is threaded or Schlieren and that of the smectic phase is focal conic fan shaped of the smectic-A type. Transition temperatures and textures of mesophases were observed through an optical polarizing microscope equipped with a heating stage. Thermal stability and mesomorphic characteristics are compared with a structurally related series. Analytical and spectral data support the structure of the molecules.
- Chauhan,Doshi,Sheth
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p. 157 - 165
(2015/12/30)
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- Synthesis of alkyl coumarate esters by celite-bound lipase of Bacillus licheniformis SCD11501
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Coumaric acid and its derivatives are known to inhibit UV-induced melanogenesis, skin erythema, angiogenesis, platelet accumulation and osteoclastogenesis besides regulation of bone formation, anti-oxidant and anti-microbial activities. The present study is a novel piece of work in which the syntheses of a series of alkyl coumarates (methyl coumarate, ethyl coumarate, propyl coumarate and butyl coumarate) have been achieved using celite-immobilized lipase of Bacillus licheniformis strain SCD11501 in a water-free medium at 55 C under shaking in a chemical reactor. The maximum yield(s) of coumaric acid based esters i.e. methyl coumarate (69.0%), ethyl coumarate (63.1%), n-propyl coumarate (59.8%) and n-butyl coumarate (55.1%) using celite-immobilized lipase could be achieved after optimizing various reaction parameters such as incubation time, incubation temperature, relative molar concentration of reactants, biocatalyst concentration and amount of molecular sieves added to the reaction system. Molecular sieves had an important effect on the ester synthesis resulting in an enhanced yield. Maximum yield was recorded for methyl coumarate (69.0%) possibly because methyl group causes less stearic hindrance to the catalytic site of the lipase due to which it becomes more accessible for immobilized lipase to undergo esterification. The characterization of synthesized esters was done through FTIR spectroscopy and 1H NMR spectra.
- Sharma, Shivika,Dogra, Priyanka,Chauhan, Ghanshyam S.,Kanwar, Shamsher S.
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- Nitrification inhibitors from the root tissues of Brachiaria humidicola, a tropical grass
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Nitrification inhibitory activity was found in root tissue extracts of Brachiaria humidicola, a tropical pasture grass. Two active inhibitory compounds were isolated by activity-guided fractionation, using recombinant Nitrosomonas europaea containing luxAB genes derived from the bioluminescent marine gram-negative bacterium Vibrio harveyi. The compounds were identified as methyl-p-coumarate and methyl ferulate, respectively. Their nitrification inhibitory properties were confirmed in chemically synthesized preparations of each. The IC50 values of chemically synthesized preparations were 19.5 and 4.4 μM, respectively. The ethyl, propyl, and butyl esters of p-coumaric and ferulic acids inhibited nitrification, whereas the free acid forms did not show inhibitory activity.
- Gopalakrishnan, Subramaniam,Subbarao, Guntur V.,Nakahara, Kazuhiko,Yoshihashi, Tadashi,Ito, Osamu,Maeda, Ikuko,Ono, Hiroshi,Yoshida, Mitsuru
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experimental part
p. 1385 - 1388
(2009/10/01)
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- Carboxylic acid esters of zosteric acid for prevention of biofouling
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Carboxylic acid ester derivatives of zosteric acid are effective in preventing biofouling and are readily formulated into coatings or films. Coating or film compositions of the esters, and methods for their application, are provided which reduce the dissolution of the esters into water or loss to the environment. The Zosteric acid esters of the invention appear to function by preventing adhesion of an organism to a surface rather than by acute toxic activity rendering said compositions more environmentally acceptable.
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Page/Page column 11
(2008/06/13)
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- Synthesis and antifungal activity of cinnamic acid esters
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Cinnamic, p-coumaric and ferulic acids were isolated from pineapple stems (Ananas comosus var. Cayenne). Twenty-four kinds of esters were prepared from these acids, alcohols and the components of Alpinia. Isopropyl 4-hydroxycinnamate (11) and butyl 4-hydroxycinnamate (12) were found to have almost the same effectiveness in antifungal activity against Pythium sp. at l0 ppm as that of the commercial fungicide iprobenfos (Kitazin P).
- Tawata,Taira,Kobamoto,Zhu,Ishihara,Toyama
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p. 909 - 910
(2007/10/03)
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- Melanin inhibitor
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A melanin inhibitor comprising as the reactive component a cinnamic acid derivative of the formula (I) or (II): STR1 in which R' represents an acyl group having 2 to 6 carbon atoms, R1 represents a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, a cycloalkyl group or an alkenyl group, and R2 represents a hydrogen atom, an alkyl group having 1 to 24 carbon atoms, a cycloalkyl group or an alkenyl group. The melanin inhibitors according to the invention are locally applied to affected portions such as of freckles and pigmentary deposits after sunburn without giving any stimulative or allergic troubles to the skin.
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