Molecular design of antifungal agents.
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.
Kubo
Isao
I
Department of Environmental Science, Policy and Management, University of California, Berkeley, California 94720-3112, USA. ikubo@uclink4.berkeley.edu
Xiao
Ping
P
Nihei
Ken-Ichi
K
Fujita
Ken-Ichi
K
Yamagiwa
Yoshiro
Y
Kamikawa
Tadao
T
D015195:Drug Design; D005659:Fungicides, Industrial / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D015394:Molecular Structure; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000254:growth & development; D013329:Structure-Activity Relationship; D013501:Surface-Active Agents / Q000494:pharmacology
D005659:Fungicides, Industrial; D013501:Surface-Active Agents; C460680:nonyl gallate; D005707:Gallic Acid