Planta Med 2012; 78 - CL2
DOI: 10.1055/s-0032-1320237

Fungal BIS-Naphthopyrones as inhibitors of botulinum neurotoxin serotype A

JH Cardellina II 1, VI Roxas-Duncan 1, V Montgomery 1, V Eccard 1, Y Campbell 1, X Hu 2, GJ Tawa 2, I Khavrutskii 2, A Wallqvist 2, JB Gloer 3, NL Phatak 3, U Höller 3, AG Soman 3, BK Joshi 3, SM Hein 3, DT Wicklow 4, LA Smith 5
  • 1Division of Integrated Toxicology, U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD
  • 2Biotechnology High Performance Computer Software Application Institute, Telemedicine and Advanced Technology Research Center, U.S. Army Medical Research and Materiel Command, Frederick, MD
  • 3Department of Chemistry, University of Iowa, Iowa City, IA
  • 4Bacterial Foodborne Pathogens and Mycology Research Unit, Agricultural Research Service, USDA, Peoria, IL
  • 5Senior Research Scientist for Medical Countermeasures Technology, U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD

An in silico screen of the NIH Molecular Library Small Molecule Repository (MLSMR) of ˜350,000 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 analogs 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.