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Antimicrob. Agents Chemother. doi:10.1128/AAC.01369-06
Copyright (c) 2006, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Pyrazinoic Acid and its n-Propyl Ester Inhibit Fatty Acid Synthase I in Replicating Tubercle Bacilli

Infectious Diseases Division, Kaplan Medical Center, affiliated to The Hebrew University, Israel; Department of Microbiology and Immunology, Howard Hughes Medical Institute, Albert Einstein College of Medicine, Bronx, New York, 10461.; Department of Chemistry, State University of New York at Albany (SUNY- Albany), Albany, NY

^* To whom correspondence should be addressed. Email: oren_z{at}clalit.org.il,

	Abstract

The activity of different analogs of pyrazinamide on Mycobacterium. tuberculosis fatty acid synthase type I in replicating bacilli was studied. Palmitic acid biosynthesis was diminished by 96% in bacilli treated with n-propyl pyrazinoate, 94% with 5-chloro-pyrazinamide, and 97% with pyrazinoic acid, the pharmacologically-active agent of pyrazinamide. We conclude that the minimal structure of pyrazine ring with an acyl group is sufficient for FASI inhibition and antimycobacterial activity..

This article has been cited by other articles:

• Ngo, S. C., Zimhony, O., Chung, W. J., Sayahi, H., Jacobs, W. R. Jr., Welch, J. T. (2007). Inhibition of Isolated Mycobacterium tuberculosis Fatty Acid Synthase I by Pyrazinamide Analogs. Antimicrob. Agents Chemother. 51: 2430-2435 [Abstract] [Full Text]