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 evaluated 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 wall polymer synthesis or assembly. Active compounds were tested for their inhibitory activities against (1,3)-beta-glucan synthase, an enzyme that catalyzes the synthesis of the major wall polymer (1,3)-beta-glucan. Although these compounds were found to be inhibitors of the enzyme (inhibition ranging between 2 and 72% at 250 micro/ml), comparison of these results with those from agar dilution assays, allow us to infer that these compounds do not act via the inhibition of glucan synthase. In addition, ketones with same pattern of substitution as alcohols, which have no antifungal properties in agar dilution assays, still displayed similar glucan synthase inhibition.