Pyrazinoic Acid and Its n -Propyl Ester Inhibit Fatty Acid Synthase Type I in Replicating Tubercle Bacilli
- 1 February 2007
- journal article
- research article
- Published by American Society for Microbiology in Antimicrobial Agents and Chemotherapy
- Vol. 51 (2), 752-754
- https://doi.org/10.1128/aac.01369-06
Abstract
The activity of different analogs of pyrazinamide on Mycobacterium tuberculosis fatty acid synthase type I (FASI) in replicating bacilli was studied. Palmitic acid biosynthesis was diminished by 96% in bacilli treated with n-propyl pyrazinoate, 94% in bacilli treated with 5-chloro-pyrazinamide, and 97% in bacilli treated 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.Keywords
This publication has 23 references indexed in Scilit:
- Mode of action of pyrazinamide: disruption of Mycobacterium tuberculosis membrane transport and energetics by pyrazinoic acidJournal of Antimicrobial Chemotherapy, 2003
- American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of AmericaAmerican Journal of Respiratory and Critical Care Medicine, 2003
- Effects of Pyrazinamide on Fatty Acid Synthesis by Whole Mycobacterial Cells and Purified Fatty Acid Synthase IJournal of Bacteriology, 2002
- Mutations in pncA, a gene encoding pyrazinamidase/nicotinamidase, cause resistance to the antituberculous drug pyrazinamide in tubercle bacillusNature Medicine, 1996
- Quantitative Structure−Activity Relationships for the in Vitro Antimycobacterial Activity of Pyrazinoic Acid EstersJournal of Medicinal Chemistry, 1996
- Pyrazinoic Acid Esters with Broad Spectrum in Vitro Antimycobacterial ActivityJournal of Medicinal Chemistry, 1995
- Activity of n-propyl pyrazinoate against pyrazinamide-resistant Mycobacterium tuberculosis: investigations into mechanism of action of and mechanism of resistance to pyrazinamideAntimicrobial Agents and Chemotherapy, 1995
- Pyrazinamide and Pyrazinoic Acid Activity against Tubercle Bacilli in Cultured Human Macrophages and in the BACTEC SystemThe Journal of Infectious Diseases, 1990
- Determination of pyrazinamide MICs for Mycobacterium tuberculosis at different pHs by the radiometric methodAntimicrobial Agents and Chemotherapy, 1988
- The sterilizing value of rifampicin and pyrazinamide in experimental short course chemotherapyTubercle, 1978