Fungal bis-Naphthopyrones as Inhibitors of Botulinum Neurotoxin Serotype A

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