Sesquiterpenes from Cultures of the Basidiomycete Clitocybe conglobata and Their 11 beta-Hydroxysteroid Dehydrogenase Inhibitory Activity

A new drimane sesquiterpenoid, 3-keto-drimenol (1), were isolated from cultures of the basidiomycete Clitocybe conglobata together with 3 beta-hydroxy-11-acetyldrimene (2), 3 beta-hydroxydrimenol (3), 11,12-dihydroxydrimene (4), 3 beta-hydroxy-11,12-O-isopropyidrimene (5), and 3 beta,11,12-trihydroxydrimene (6). Their structures were established from MS and NMR experiments. Compounds 1, 3, and 6 showed inhibitory activities against two isozymes of 11 beta-hydroxysteroid dehydrogenases with IC50 1.7-8.0 mu g/ml (human 11 beta-HSD1), 10.7-24.1 mu g/ml (mouse 11 beta-HSD1); 177.0-220.0 mu g/ml (human 11 beta-HSD2),250.5-500.2 mu g/ml (mouse 11 beta-HSD2), respectively, which catalyze the interconversion of active cortisol and inactive cortisone.