Auckland Cancer Society Research Centre, School of Medical Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand.
Future Med Chem. 2010 Aug;2(8):1295-304. doi: 10.4155/fmc.10.207.
PA-824 is an experimental anti-tubercular agent that has a novel mechanism of action. It is effective against both active and persistent forms of the disease and has recently shown early bactericidal activity in a Phase II clinical trial. This review summarizes recent studies on the mode of action of PA-824 and outlines successful efforts to prepare more effective second-generation analogs. PA-824 displays unusual chemistry following both enzymatic and radiolytic reduction, which is clearly related to its activity as an anti-tubercular agent. The nitroreductase enzyme deazaflavin-dependent nitroreductase, reduces PA-824 with loss of the nitro group, generating reactive nitrogen species such as nitric oxide, which appear important in mediating the activity of the drug. Bioreductive drugs such as PA-824 hold the promise of shorter treatment regimens.
PA-824 是一种实验性抗结核药物，具有新颖的作用机制。它对活跃和持续形式的疾病都有效，并且最近在 II 期临床试验中显示出早期杀菌活性。这篇综述总结了 PA-824 的作用模式的最新研究，并概述了制备更有效的第二代类似物的成功努力。PA-824 在酶促和辐射还原后表现出异常的化学性质，这显然与其作为抗结核药物的活性有关。硝基还原酶酶脱氮黄素依赖的硝基还原酶，使 PA-824 失去硝基，生成活性氮物质，如一氧化氮，这似乎在介导药物活性中很重要。像 PA-824 这样的生物还原药物有望缩短治疗方案。
