正丙基吡嗪酸酯对耐吡嗪酰胺结核分枝杆菌的活性：吡嗪酰胺作用机制及耐药机制的研究
Activity of n-propyl pyrazinoate against pyrazinamide-resistant Mycobacterium tuberculosis: investigations into mechanism of action of and mechanism of resistance to pyrazinamide.
作者信息
Speirs R J, Welch J T, Cynamon M H
机构信息
Veterans Affairs Medical Center, Syracuse, New York 13210, USA.
出版信息
Antimicrob Agents Chemother. 1995 Jun;39(6):1269-71. doi: 10.1128/AAC.39.6.1269.
Abstract
The mechanism of action of pyrazinamide (PZA) is not known. One hypothesis is that PZA functions as a prodrug of pyrazinoic acid. Susceptibility to PZA correlates with amidase activity of the Mycobacterium tuberculosis isolate in question. PZA-resistant isolates retain susceptibility in vitro to pyrazinoic acid and n-propyl pyrazinoate. Esters of pyrazinoic acid appear to circumvent the requirement for activation by mycobacterial amidase. The MICs of n-propyl pyrazinoate for M. tuberculosis isolates are lower than those of pyrazinoic acid. Further studies to assess the effects of modifications of the alcohol and pyrazine moieties of pyrazinoate esters on in vitro and in vivo antituberculosis activity are under way. This may lead to a candidate compound with enhanced activity against both PZA-susceptible and PZA-resistant M. tuberculosis isolates suitable for clinical development.
摘要
吡嗪酰胺（PZA）的作用机制尚不清楚。一种假说认为，PZA作为吡嗪酸的前体药物发挥作用。对PZA的敏感性与所讨论的结核分枝杆菌分离株的酰胺酶活性相关。对PZA耐药的分离株在体外对吡嗪酸和吡嗪酸正丙酯仍敏感。吡嗪酸酯似乎绕过了被分枝杆菌酰胺酶激活的需求。吡嗪酸正丙酯对结核分枝杆菌分离株的最低抑菌浓度低于吡嗪酸。正在进行进一步研究，以评估吡嗪酸酯的醇和吡嗪部分修饰对体外和体内抗结核活性的影响。这可能会产生一种对PZA敏感和耐药的结核分枝杆菌分离株均具有增强活性的候选化合物，适合进行临床开发。
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