Pyrazinoic acid and its n-propyl ester inhibit fatty acid synthase type I in replicating tubercle bacilli.
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.
Zimhony
Oren
O
Infectious Diseases Division, Kaplan Medical Center, The Hebrew University and Hadassah Jerusalem, P.O. Box 1, Rehovot 76100, Israel. oren_z@clalit.org.il
Vilchèze
Catherine
C
Arai
Masayoshi
M
Welch
John T
JT
Jacobs
William R
WR
D001426:Bacterial Proteins / Q000037:antagonists & inhibitors*; D064429:Fatty Acid Synthases / Q000037:antagonists & inhibitors*; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D011718:Pyrazinamide / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014376:Tuberculosis / Q000188:drug therapy / Q000382:microbiology
C111084:5-chloropyrazinamide; D001426:Bacterial Proteins; D011718:Pyrazinamide; C005296:pyrazinoic acid; C095794:propyl pyrazinoate; D064429:Fatty Acid Synthases; C413881:fatty acid synthase I, mycobacteria