Abstrakt

Stability, activation and antymycobacterial activity of pyrazinoic acid esters

Constantino. L

 Tuberculosis is a leading infectious cause of morbility and mortality world-wide, especially in developing countries Pyrazinamide (PZA), a first line agent for the treatment of tuberculosis, is itself a prodrug that requires activation by the bacterial pyrazinamidase to form its active metabolite pyrazinoic acid (POA) 2, which has poor absorption and significant serum binding. Resistance to PZA is attributed to mutations in the mycobacterial gene encoding pyrazinamidase. Since PZA is in fact a prodrug of POA, other prodrugs, like esters 3, could have activity against M. tuberculosis.