Fungal bis-Naphthopyrones as Inhibitors of Botulinum Neurotoxin Serotype A

ACS Med Chem Lett. 2012 Apr 2;3(5):387-91. doi: 10.1021/ml200312s. eCollection 2012 May 10.


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 (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.

Keywords: binding free energy; botulinum neurotoxin serotype A; chaetochromin; in silico screen; natural products; talaroderxine; thermodynamic integration.