Studies of Platelet Activating Factor (PAF) Antagonists from Microbial Products. I. : Bisdethiobis(methylthio)gliotoxin and Its Derivatives

Abstract

A platelet activating factor (PAF) antagonist, designated as FR-49175, was isolated from fermentation products of Penicillium terlikowskii and identified as bisdethiobis(methylthio)-gliotoxin (1). The IC₅₀ value of this compound for PAF-induced rabbit platelet aggregation was 8.4 μM.Some derivatives of bisdethiobis(methylthio)gliotoxin (1) were synthesized and their inhibitory activities of PAF-induced platelet aggregation were examined. Among these compounds, 5a, 6-anhydrobisdethio-3, 10a-bis(methylthio)gliotoxin (8) showed the most potent PAF inhibitory activity (IC₅₀; 4.4 μM).