pyrazinamide brands

Molecular formula: C5H5N3O

Pyrazinamide diffuses into active _M. tuberculosis_ that express pyrazinamidase enzyme that converts pyrazinamide to the active form pyrazinoic acid. Pyrazinoic acid can leak out under acidic conditions to be converted to the protonated conjugate acid, which is readily diffused back into the bacilli and accumulate intracellularly. The net effect is that more pyrazinoic acid accumulates inside the bacillus at acid pH than at neutral pH. Pyrazinoic acid was thought to inhibit the enzyme fatty acid synthase (FAS) I, which is required by the bacterium to synthesise fatty acids. However, this theory was thought to have been discounted. However, further studies reproduced the results of FAS I inhibition as the putative mechanism first in whole cell assay of replicating M. tuberculosis bacilli which have shown that pyrazinoic acid and its ester inhibit the synthesis of fatty acids. This study was followed by in vitro assay of tuberculous FAS I enzyme that tested the activity with pyrazinamide, pyrazinoic acid and several classes of pyrazinamide analogs. Pyrazinamide and its analogs inhibited the activity of purified FAS I. It has also been 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 has also been shown to bind to the ribosomal protein S1 (RpsA) and inhibit trans-translation. This may explain the ability of the drug to kill dormant mycobacteria. Pyrazinamide may be bacteriostatic or bactericidal in action, depending on the concentration of the drug attained at the site of the infection and the susceptibility of the infecting organism. In vitro and in vivo, the drug is active only at a slightly acidic pH. The exact mechanism of action of pyrazinamide has not been fully elucidated. The antimycobacterial activity of pyrazinamide appears to partly depend on conversion of the drug to pyrazinoic acid. Susceptible strains of Mycobacterium tuberculosis produce pyrazinamidase, an enzyme that deaminates pyrazinamide to pyrazinoic acid, and the in vitro susceptibility of a given strain of the organism appears to correspond to its pyrazinamidase activity. In vitro studies indicate that pyrazinoic acid has specific antimycobacterial activity against Mycobacterium tuberculosis. In addition, the fact that pyrazinoic acid lowers the pH of the environment below that which is necessary for growth of Mycobacterium tuberculosis appears to contribute to the drug's antimycobacterial activity in vitro. Unknown; pyrazinamide may be bacteriostatic or bactericidal, depending on its concentration and the susceptibility of the organism. It is active in vitro at an acidic pH of 5.6 or less, similar to that found in early, active tubercular inflammatory lesions.

Source: PubChem (NCBI) · compound 1046