title: 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.
authors.affiliation: Department of Environmental Science, Policy and Management, University of California, Berkeley, California 94720-3112, USA. ikubo@uclink4.berkeley.edu
authors.forename: Isao
authors.initials: I
authors.lastname: Kubo
authors.forename: Ping
authors.initials: P
authors.lastname: Xiao
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Nihei
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Fujita
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Yamagiwa
authors.forename: Tadao
authors.initials: T
authors.lastname: Kamikawa
mesh_terms: 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
chemical_list: D005659:Fungicides, Industrial; D013501:Surface-Active Agents; C460680:nonyl gallate; D005707:Gallic Acid