Pyrazinamide is a pyrazine that is used therapeutically as an antitubercular agent.Target: AntibacterialPyrazinamide is a prodrug that stops the growth of Mycobacterium tuberculosis. Pyrazinoic acid was thought to inhibit the enzyme fatty acid synthase (FAS) I, which is required by the bacterium to synthesise fatty acids although this has been discounted. It was also suggested that the accumulation of pyrazinoic acid disrupts membrane potential and interferes with energy production, necessary for survival of M. tuberculosis at an acidic site of infection. Pyrazinoic acid binds to the ribosomal protein S1 (RpsA) and inhibits trans-translation. This may explain the ability of the drug to kill dormant mycobacteria [1-4].
References:
[1]. Zhang, Y. and D. Mitchison, The curious characteristics of pyrazinamide: a review. Int J Tuberc Lung Dis, 2003. 7(1): p. 6-21.
[2]. Zimhony, O., et al., Pyrazinamide inhibits the eukaryotic-like fatty acid synthetase I (FASI) of Mycobacterium tuberculosis. Nat Med, 2000. 6(9): p. 1043-7.
[3]. Boshoff, H.I., V. Mizrahi, and C.E. Barry, 3rd, Effects of pyrazinamide on fatty acid synthesis by whole mycobacterial cells and purified fatty acid synthase I. J Bacteriol, 2002. 184(8): p. 2167-72.
[4]. Shi, W., et al., Pyrazinamide inhibits trans-translation in Mycobacterium tuberculosis. Science, 2011. 333(6049): p. 1630-2.