A new series of natural antifungals that inhibit p 450 lanosterol c-14 demethylase: II. Mode of action

Abstract

From a Penicillium sp. we identified a new series of antifungals having a tetrahydropyran skeleton with an alkenyl side chain. We elucidated the mode of action of Ro 09-1470, the most active compound of the series. Treatment of Candida albicans with the compound caused an accumulation of C-14 methyl intermediates of ergosterol at concentrations of which no significant interference with the biosyntheses of other macromolecules and respiration was observed. p 450 lanosterol C-14 demethylase (p 45014DM) activity was inhibited and furthermore, the binding of Ro 09-1470 to the heme of the enzyme was demonstrated by a difference spectrum. We conclude that Ro 09-1470 is the first natural antifungal that inhibits the p 45014DM of fungi. © 1992, JAPAN ANTIBIOTICS RESEARCH ASSOCIATION. All rights reserved.