Ang Chee Wei, Jarrad Angie M, Cooper Matthew A, Blaskovich Mark A T
The Institute for Molecular Bioscience, The University of Queensland , St Lucia, Queensland 4072, Australia.
J Med Chem. 2017 Sep 28;60(18):7636-7657. doi: 10.1021/acs.jmedchem.7b00143. Epub 2017 May 22.
Infectious diseases claim millions of lives every year, but with the advent of drug resistance, therapeutic options to treat infections are inadequate. There is now an urgent need to develop new and effective treatments. Nitroimidazoles are a class of antimicrobial drugs that have remarkable broad spectrum activity against parasites, mycobacteria, and anaerobic Gram-positive and Gram-negative bacteria. While nitroimidazoles were discovered in the 1950s, there has been renewed interest in their therapeutic potential, particularly for the treatment of parasitic infections and tuberculosis. In this review, we summarize different classes of nitroimidazoles that have been described in the literature in the past five years, from approved drugs and clinical candidates to examples undergoing preclinical or early stage development. The relatively "nonspecific" mode of action and resistance mechanisms of nitromidazoles are discussed, and contemporary strategies to facilitate nitroimidazole drug development are highlighted.
传染病每年夺去数百万人的生命，但随着耐药性的出现，治疗感染的选择并不充足。目前迫切需要开发新的有效治疗方法。硝基咪唑类是一类抗菌药物，对寄生虫、分枝杆菌以及厌氧革兰氏阳性菌和革兰氏阴性菌具有显著的广谱活性。虽然硝基咪唑类药物在20世纪50年代就已被发现，但人们对其治疗潜力重新产生了兴趣，特别是在治疗寄生虫感染和结核病方面。在本综述中，我们总结了过去五年文献中描述的不同类别的硝基咪唑类药物，从已批准的药物和临床候选药物到正在进行临床前或早期开发的例子。讨论了硝基咪唑类药物相对“非特异性”的作用方式和耐药机制，并强调了促进硝基咪唑类药物开发的当代策略。
