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J Med Chem. 2005 Mar 10;48(5):1596-609.

Structure-based design, synthesis, and study of potent inhibitors of beta-ketoacyl-acyl carrier protein synthase III as potential antimicrobial agents.

Author information

1
Departments of Medicinal Chemistry, Protein Biochemistry and Structural Biology, Quorex Pharmaceuticals Inc., 1890 Rutherford Road, Suite 200, Carlsbad, CA 92008, USA. zhenie@phoenixpharmaco.com

Abstract

Fatty acid biosynthesis is essential for bacterial survival. Components of this biosynthetic pathway have been identified as attractive targets for the development of new antibacterial agents. FabH, beta-ketoacyl-ACP synthase III, is a particularly attractive target, since it is central to the initiation of fatty acid biosynthesis and is highly conserved among Gram-positive and -negative bacteria. Small molecules that inhibit FabH enzymatic activity have the potential to be candidates within a novel class of selective, nontoxic, broad-spectrum antibacterials. Using crystallographic structural information on these highly conserved active sites and structure based drug design principles, a benzoylaminobenzoic acid series of compounds was developed as potent inhibitors of FabH. This inhibitor class demonstrates strong antibacterial activity against Gram-positive and selected Gram-negative organisms.

PMID:
15743201
DOI:
10.1021/jm049141s
[Indexed for MEDLINE]

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