Fungal bis-Naphthopyrones as Inhibitors of Botulinum Neurotoxin Serotype A.

摘要

An in silico screen of the NIH Molecular Library Small Molecule Repository (MLSMR) of approximately 350000 compounds and confirmatory bioassays led to identification of chaetochromin A (1) as an inhibitor of botulinum neurotoxin serotype A (BoNT A). Subsequent acquisition and testing of analogues of 1 uncovered two compounds, talaroderxines A (2) and B (3), with improved activity. These are the first fungal metabolites reported to exhibit BoNT/A inhibitory activity.