Molecular Design of Antifungal Agents

Abstract

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 microg/mL (42 microM), followed by octyl gallate (2) with an MFC of 25 microg/mL (89 microM). 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.

Inhibitive Effects of Alkyl Gallates on Hyaluronidase and Collagenase

“…9,10) The gallate esters of n-alkanols also act as potent antioxidants, and propyl, octyl, and dodecyl (lauryl) gallates are permitted additives for antioxidation in foods in the United States 11) although they are not natural compounds. Furthermore, some of these alkyl gallates, including octyl gallate, have been reported to be useful as multifunctional food additives, as they have antibrowning, 12) antifungal, 13) and antibacterial 14) effects. To determine whether alkyl gallates are also useful as cosmeceutical ingredients, in the present study, we have identified their inhibitory activities against hyaluronidase and collagenase.…”

“…15) To confirm the structure of the synthesized products, the 1 H-NMR spectrum was recorded on a JEOL JNM-AL400 spectrometer (400 MHz) in deuterium methanol and compared with previously reported data. 12,13,[15][16][17] To evaluate radical scavenging activity against the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, a sample (alkyl gallate) was dissolved in 2 ml of methanol and mixed with 0.5 ml of a DPPH solution (0.4 mg/ml) in methanol. After incubation at room temperature for 30 min in air, the remaining DPPH was determined by measuring the absorbance at 520 nm, and the radicalscavenging activity was estimated as described by Yoshida et al…”

New aspect of gallic esters: marked effect on termite feeding

“…6) Gallic esters are known to have various bioactivities, including anti-oxidative, anti-browning, anti-bacterial, anti-fungal activities. [7][8][9][10][11][12][13] We herein report that their effects on termite feeding are altered by carbon chain lengths.…”

Antimicrobial Activity of Ethanol Extract from Leaves ofCasearia sylvestris.

“…Shibata et al (2005) verified that the presence of alkyl gallates synergistically increases the sensitivity of S. aureus to β-lactam antibiotics. Also, Kubo et al (2002) showed that S. cerevisiae is sensitive to alkyl gallate derivatives with bigger hydrophobicity index. We have verified that MGDE was in a general way less efficient than IGDE for inhibiting microbial growth.…”