title: Fungal bis-Naphthopyrones as Inhibitors of Botulinum Neurotoxin Serotype A.
abstract: 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.
authors.affiliation: Division of Integrated Toxicology, U.S. Army Medical Research Institute of Infectious Diseases , Frederick, Maryland 21702-5011.
authors.forename: John H
authors.initials: JH
authors.lastname: Cardellina
authors.affiliation: Division of Integrated Toxicology, U.S. Army Medical Research Institute of Infectious Diseases , Frederick, Maryland 21702-5011.
authors.forename: Virginia I
authors.initials: VI
authors.lastname: Roxas-Duncan
authors.affiliation: Division of Integrated Toxicology, U.S. Army Medical Research Institute of Infectious Diseases , Frederick, Maryland 21702-5011.
authors.forename: Vicki
authors.initials: V
authors.lastname: Montgomery
authors.affiliation: Division of Integrated Toxicology, U.S. Army Medical Research Institute of Infectious Diseases , Frederick, Maryland 21702-5011.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Eccard
authors.affiliation: Division of Integrated Toxicology, U.S. Army Medical Research Institute of Infectious Diseases , Frederick, Maryland 21702-5011.
authors.forename: Yvette
authors.initials: Y
authors.lastname: Campbell
authors.affiliation: Biotechnology High Performance Computer Software Applications Institute, Telemedicine and Advanced Technology Research Center, U.S. Army Medical Research and Materiel Command , Frederick, Maryland 21702.
authors.forename: Xin
authors.initials: X
authors.lastname: Hu
authors.affiliation: Biotechnology High Performance Computer Software Applications Institute, Telemedicine and Advanced Technology Research Center, U.S. Army Medical Research and Materiel Command , Frederick, Maryland 21702.
authors.forename: Ilja
authors.initials: I
authors.lastname: Khavrutskii
authors.affiliation: Biotechnology High Performance Computer Software Applications Institute, Telemedicine and Advanced Technology Research Center, U.S. Army Medical Research and Materiel Command , Frederick, Maryland 21702.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Tawa
authors.affiliation: Biotechnology High Performance Computer Software Applications Institute, Telemedicine and Advanced Technology Research Center, U.S. Army Medical Research and Materiel Command , Frederick, Maryland 21702.
authors.forename: Anders
authors.initials: A
authors.lastname: Wallqvist
authors.affiliation: Department of Chemistry, University of Iowa , Iowa City, Iowa 52242-1294.
authors.forename: James B
authors.initials: JB
authors.lastname: Gloer
authors.affiliation: Department of Chemistry, University of Iowa , Iowa City, Iowa 52242-1294.
authors.forename: Nisarga L
authors.initials: NL
authors.lastname: Phatak
authors.affiliation: Department of Chemistry, University of Iowa , Iowa City, Iowa 52242-1294.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Höller
authors.affiliation: Department of Chemistry, University of Iowa , Iowa City, Iowa 52242-1294.
authors.forename: Ashish G
authors.initials: AG
authors.lastname: Soman
authors.affiliation: Department of Chemistry, University of Iowa , Iowa City, Iowa 52242-1294.
authors.forename: Biren K
authors.initials: BK
authors.lastname: Joshi
authors.affiliation: Department of Chemistry, University of Iowa , Iowa City, Iowa 52242-1294.
authors.forename: Sara M
authors.initials: SM
authors.lastname: Hein
authors.affiliation: Bacterial Foodborne Pathogens and Mycology Research Unit, Agricultural Research Service, U.S. Department of Agriculture , Peoria, Illinois 61604.
authors.forename: Donald T
authors.initials: DT
authors.lastname: Wicklow
authors.affiliation: Senior Research Scientist for Medical Countermeasures Technology, U.S. Army Medical Research Institute of Infectious Diseases , Frederick, Maryland 21702-5011.
authors.forename: Leonard A
authors.initials: LA
authors.lastname: Smith
keywords: binding free energy; botulinum neurotoxin serotype A; chaetochromin; in silico screen; natural products; talaroderxine; thermodynamic integration