IN-VITRO STUDIES ON MODE OF ACTION OF ANTIFUNGAL 8.O.4'-NEOLIGNANS OCCURRING IN CERTAIN SPECIES OF VIROLA AND RELATED GENERA OF MYRISTICACEAE

Neutral racemic antifungal alcohols of 8.O.4'-neolignan type, were eva luated for inhibitory activity towards the fungal cell wall, using the whole cell Neurospora crassa hyphal growth inhibition assay. Results strongly suggested that these compounds could act by inhibiting cell w all polymer synthesis or assembly. Active compounds were tested for th eir inhibitory activities against (1,3)-beta-glucan synthase, an enzym e that catalyzes the synthesis of the major wall polymer (l,3)-beta-gl ucan. Although these compounds were found to be inhibitors of the enzy me (inhibition ranging between 2 and 72% at 250 mu g/ml), comparison o f these results with those from agar dilution assays, allow us to infe r that these compounds do not act via the inhibition of glucan synthas e. In addition, ketones with same pattern of substitution as alcohols, which have no antifungal properties in agar dilution assays, still di splayed similar glucan synthase inhibition. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.