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 .mu.M. Some derivatives of bisdethiobis(methylthio)gliotoxin (1) were synthesized and their inhibitory activities on 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 .mu.M).

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