Fungal bis-Naphthopyrones as Inhibitors of Botulinum Neurotoxin Serotype A

John H Cardellina; Virginia I Roxas-Duncan; Vicki Montgomery; Vanessa Eccard; Yvette Campbell; Xin Hu; Ilja Khavrutskii; Gregory J Tawa; Anders Wallqvist; James B Gloer; Nisarga L Phatak; Ulrich Höller; Ashish G Soman; Biren K Joshi; Sara M Hein; Donald T Wicklow; Leonard A Smith

doi:10.1021/ml200312s

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Fungal bis-Naphthopyrones as Inhibitors of Botulinum Neurotoxin Serotype A

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Fungal bis-Naphthopyrones as Inhibitors of Botulinum Neurotoxin Serotype A

John H Cardellina, Virginia I Roxas-Duncan, Vicki Montgomery, Vanessa Eccard, Yvette Campbell, Xin Hu, Ilja Khavrutskii, Gregory J Tawa, Anders Wallqvist, James B Gloer, …

ACS Medicinal Chemistry Letters, Vol.3(5), pp.387-391

05/10/2012

DOI: 10.1021/ml200312s

PMCID: PMC4025784

PMID: 24900483

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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.

Letter

natural products

chaetochromin

botulinum neurotoxin serotype A

thermodynamic integration

binding free energy

talaroderxine

in silico screen

Details

Title: Subtitle: Fungal bis-Naphthopyrones as Inhibitors of Botulinum Neurotoxin Serotype A
Creators: John H Cardellina - U.S. Army Medical Research Institute of Infectious Diseases
Virginia I Roxas-Duncan - U.S. Army Medical Research Institute of Infectious Diseases
Vicki Montgomery - U.S. Army Medical Research Institute of Infectious Diseases
Vanessa Eccard - U.S. Army Medical Research Institute of Infectious Diseases
Yvette Campbell - U.S. Army Medical Research Institute of Infectious Diseases
Xin Hu - U.S. Army Medical Research and Materiel Command
Ilja Khavrutskii - U.S. Army Medical Research and Materiel Command
Gregory J Tawa - U.S. Army Medical Research and Materiel Command
Anders Wallqvist - U.S. Army Medical Research and Materiel Command
James B Gloer - University of Iowa
Nisarga L Phatak - University of Iowa
Ulrich Höller - University of Iowa
Ashish G Soman - University of Iowa
Biren K Joshi - University of Iowa
Sara M Hein - University of Iowa
Donald T Wicklow - U.S. Department of Agriculture
Leonard A Smith - U.S. Army Medical Research Institute of Infectious Diseases
Resource Type: Journal article
Publication Details: ACS Medicinal Chemistry Letters, Vol.3(5), pp.387-391
DOI: 10.1021/ml200312s
PMID: 24900483
PMCID: PMC4025784
NLM abbreviation: ACS Med Chem Lett
ISSN: 1948-5875
eISSN: 1948-5875
Publisher: American Chemical Society
Language: English
Date published: 05/10/2012
Academic Unit: Chemistry
Record Identifier: 9983986096702771

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