Citrinin hydrate inhibits serotonin N-acetyltransferase catalyzing the conversion of serotonin to N-acetylserotonin

Abstract

In an attempt to search for serotonin N-acetyltransferase (arylalkylamine N-acetyltransferase, AA-NAT) inhibitors from microbial metabolites, we found the culture broth of Penicillium sp. 80722 which showed a strong inhibitory activity against AA-NAT. The active principle has been identified as citrinin hydrate through bioassay-guided fractionation of cultural broth, and structure elucidation derived by spectroscopic analyses. Citrinin hydrate inhibits AA-NAT with an IC50 value of 173 μM in a dose-dependent manner. Although citrinin hydrate was previously isolated as human rhinovirus 3C-protease inhibitor, this was recognized as the first AA-NAT inhibitor isolated from natural sources.