Small molecule inhibitors of anthrax lethal factor toxin

John D Williams; Atiyya R Khan; Steven C Cardinale; Michelle M Butler; Terry L Bowlin; Norton P Peet

doi:10.1016/j.bmc.2013.11.009

Small molecule inhibitors of anthrax lethal factor toxin

Bioorg Med Chem. 2014 Jan 1;22(1):419-34. doi: 10.1016/j.bmc.2013.11.009. Epub 2013 Nov 13.

Authors

John D Williams¹, Atiyya R Khan¹, Steven C Cardinale¹, Michelle M Butler¹, Terry L Bowlin¹, Norton P Peet²

Affiliations

¹ Microbiotix, Inc., Department of Medicinal Chemistry, One Innovation Drive, Worcester, MA 01605, United States; Microbiotix, Inc., Department of Molecular Biology, One Innovation Drive, Worcester, MA 01605, United States.
² Microbiotix, Inc., Department of Medicinal Chemistry, One Innovation Drive, Worcester, MA 01605, United States; Microbiotix, Inc., Department of Molecular Biology, One Innovation Drive, Worcester, MA 01605, United States. Electronic address: npeet@comcast.net.

Abstract

This manuscript describes the preparation of new small molecule inhibitors of Bacillus anthracis lethal factor. Our starting point was the symmetrical, bis-quinolinyl compound 1 (NSC 12155). Optimization of one half of this molecule led to new LF inhibitors that were desymmetrized to afford more drug-like compounds.

Keywords: Anthrax; Bacillus anthracis; Botulinum neurotoxin A; Desymmetrized; Hybrid compound; Lethal factor; Light chain; Matrix metalloprotease; Quinoline; Zinc metalloprotease.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Antigens, Bacterial / chemistry*
Bacillus anthracis / growth & development*
Bacterial Toxins / chemistry*
Humans
Models, Molecular

Substances

Antigens, Bacterial
Bacterial Toxins
anthrax toxin

Grants and funding

R43 AI066476/AI/NIAID NIH HHS/United States