- Design, Synthesis, and Antifungal Activity of Alkyl Gallates Against Plant Pathogenic Fungi In Vitro and In Vivo
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A series of alkyl gallates was synthesized by reacting gallic acid with the corresponding alcohols. Their structures were determined on the basis of spectroscopic data, including NMR and MS. The antifungal activities of these compounds against plant pathogenic fungi in vitro and in vivo were assessed.
- Zhao, Xiao-Long,Li, Chun-Qing,Song, Xiao-Mei,Yan, Shuang-Mei,Luo, Du-Qiang
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- Antifungal activity of alkyl gallates against plant pathogenic fungi
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The antifungal activity of alkyl gallates against plant pathogenic fungi was evaluated. All of the fungi tested in this study were susceptible to some alkyl gallates, and the effect of linear alkyl gallates against plant pathogenic fungi was similar to the previously reported effects against Gram-negative and Gram-positive bacteria. We found that branched alkyl gallates showed stronger activity than did linear alkyl gallates with similar log P values. In addition, the antifungal activity of alkyl gallates was correlated with gallate-induced inhibition of the activity of mitochondrial complex II. The antifungal activity of alkyl gallates likely originates, at least in part, from their ability to inhibit the membrane respiratory chain.
- Ito, Shinsaku,Nakagawa, Yasutaka,Yazawa, Satoru,Sasaki, Yasuyuki,Yajima, Shunsuke
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p. 1812 - 1814
(2014/04/17)
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- Alkyl hydroxybenzoic acid derivatives that inhibit HIV-1 protease dimerization
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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, Kid 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.
- Flausino Jr., O. A.,Dufau, L.,Reboud-Ravaux, M.,Regasini, L. O.,Petronio, M. S.,Silva, D. H. S.,Bolzani, V. S.,Rose, T.
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p. 4534 - 4540,7
(2012/12/12)
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- Inhibitive effects of alkyl gallates on Hyaluronidase and collagenase
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A series of the gallate esters of n-alkanols (C1-C12) was examined to determine their inhibitory activities against hyaluronidase and collagenase. Hexyl, heptyl, octyl, nonyl, and decyl gallates inhibited both hyaluronidase and collagenase, and the most potent inhibitor was octyl gallate against both enzymes. Octyl 3, 5- dihydroxybenzoate showed inhibitory effects on hyaluronidase, whereas collagenase was inhibited by octyl 3, 4-dihydroxybenzoate.
- Barla, Florin,Higashijima, Hayato,Funai, Shingo,Sugimoto, Keiichiro,Harada, Naoki,Yamaji, Ryoichi,Fujita, Tomoyuki,Nakano, Yoshihisa,Inui, Hiroshi
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body text
p. 2335 - 2337
(2010/07/17)
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- Alkyl gallates, intensifiers of β-lactam susceptibility in methicillin-resistant Staphylococcus aureus
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We found that ethyl gallate purified from a dried pod of tara (Caesalpinia spinosa) intensified β-lactam susceptibility in methicillin-resistant and methicillin-sensitive strains of Staphylococcus aureus (MRSA and MSSA strains, respectively). This compound and several known alkyl gallates were tested with MRSA and MSSA strains to gain new insights into their structural functions in relation to antimicrobial and β-lactam susceptibility-intensifying activities. The maximum activity of alkyl gallates against MRSA and MSSA strains occurred at 1-nonyl and 1-decyl gallate, with an MIC at which 90% of the isolates tested were inhibited of 15.6 μg/ml. At concentrations lower than the MIC, alkyl gallates synergistically elevated the susceptibility of MRSA and MSSA strains to β-lactam antibiotics. Such a synergistic activity of the alkyl gallates appears to be specific for β-lactam antibiotics, because no significant changes were observed in the MICs of other classes of antibiotics examined in this study. The length of the alkyl chain was also associated with the modifying activity of the alkyl gallates, and the optimum length was C5 to C6. The present work clearly demonstrates that the length of the alkyl chain has a key role in the elevation of susceptibility to β-lactam antibiotics.
- Shibata, Hirofumi,Kondo, Kyoko,Katsuyama, Ryo,Kawazoe, Kazuyoshi,Sato, Yoichi,Murakami, Kotaro,Takaishi, Yoshihisa,Arakaki, Naokatu,Higuti, Tomihiko
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p. 549 - 555
(2007/10/03)
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- Molecular design of antifungal agents
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In a rational approach to the design of antifungal agents against Saccharomyces cerevisiae, a series of alkyl gallates (3,4,5-trihydroxybenzoates) were synthesized and assayed. Nonyl gallate (1) was found to be the most effective with a minimum fungicidal concentration (MFC) of 12.5 μg/mL (42 μM), followed by octyl gallate (2) with an MFC of 25 μg/mL (89 μM). These MFCs are little influenced by pH values. A time-kill curve study indicates that nonyl gallate exhibits fungicidal activity against S. cerevisiae at any growing stage. The antifungal activity of nonyl gallate is due primarily to its ability to act as a nonionic surface-active agent (surfactant). The length of the alkyl group is not a major contributor but plays a role in eliciting the activity to a large extent. As far as alkyl gallates are concerned, their antimicrobial spectra and potency depend largely on the hydrophobic portion of the molecules.
- Kubo, Isao,Xiao, Ping,Nihei, Ken-Ichi,Fujita, Ken-Ichi,Yamagiwa, Yoshiro,Kamikawa, Tadao
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p. 3992 - 3998
(2007/10/03)
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- Anti-Salmonella activity of alkyl gallates
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A series of alkyl gallates (3,4,5-trihydroxybenzoates) was synthesized and tested for their antibacterial activity against Salmonella choleraesuis. Nonyl (C9) and octyl (C8) gallates were noted to be the most effective against this food-borne bacterium, each with a minimum bactericidal concentration (MBC) of 12.5 μg/mL, followed by decyl (C10) gallate, with a MBC of 25 μg/mL. Dodecyl (C12) gallate exhibited activity against S. choleraesuis, with a MBC of 50 μg/mL. Propyl (C3) gallate showed no activity against S. choleraesuis up to 3200 μg/mL. The length of the alkyl group is not a major contributor but plays a role in eliciting the activity to a large extent. The same series of alkyl gallates, regardless of alkyl chain length, all showed nearly the same potent scavenging activity on the 1,1-diphenyl-2-picrylhydrazyl radical, indicating that the length of the alkyl group is not associated with the activity.
- Kubo, Isao,Fujita, Ken-Ichi,Nihei, Ken-Ichi
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p. 6692 - 6696
(2007/10/03)
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