Neochetracin: An Unusual Chetracin-Type Epithiodiketopiperazine Derivative Produced by the Fungus Amesia atrobrunnea

Abstract

Epithiodiketopiperazines are a widely distributed class of secondary metabolites originating from an NRPS biosynthetic pathway and featuring diverse biological activities. In this study, the soil-borne fungus Amesia atrobrunnea FMR 19325 was found to produce a novel chetracin-like epithiodiketopiperazine, neochetracin (1), featuring a unique C-11a'-S-N cross-linkage, along with the known congener, chetracin B (2). Chemical structures were elucidated based on HR-ESI-MS and comprehensive 1D/2D NMR spectroscopic analyses. The relative configuration of 1 was distinguished based on a ROESY experiment while its absolute configuration remains undetermined. Chetracin B was found to be a more potent cytotoxic agent compared with its new congener. Compounds 1 and 2 also exerted strong antibacterial effects against the tested bacteria; however, our results suggested that the presence of the C-11a'-S-N cross-linkage in 1 resulted in the total or partial loss of activity against Gram-negative bacteria.