Fan Yi-Lei, Jin Xiao-Hong, Huang Zhong-Ping, Yu Hai-Feng, Zeng Zhi-Gang, Gao Tao, Feng Lian-Shun
Key Laboratory of Drug Prevention and Control Technology of Zhejiang Province, Zhejiang Police College, Hangzhou, PR China.
School of Nuclear Technology and Chemistry & Biology, Hubei University of Science and Technology, Xianning 437100, PR China.
Eur J Med Chem. 2018 Apr 25;150:347-365. doi: 10.1016/j.ejmech.2018.03.016. Epub 2018 Mar 7.
Tuberculosis still remains one of the most common, communicable, and leading deadliest diseases known to mankind throughout the world. Drug-resistance in Mycobacterium tuberculosis which threatens to worsen the global tuberculosis epidemic has caused great concern in recent years. To overcome the resistance, the development of new drugs with novel mechanisms of actions is of great importance. Imidazole-containing derivatives endow with various biological properties, and some of them demonstrated excellent anti-tubercular activity. As the most emblematic example, 4-nitroimidazole delamanid has already received approval for treatment of multidrug-resistant tuberculosis infected patients. Thus, imidazole-containing derivatives have caused great interests in discovery of new anti-tubercular agents. Numerous of imidazole-containing derivatives were synthesized and screened for their in vitro and in vivo anti-mycobacterial activities against both drug-sensitive and drug-resistant Mycobacterium tuberculosis pathogens. This review aims to outline the recent advances of imidazole-containing derivatives as anti-tubercular agents, and summarize the structure-activity relationship of these derivatives. The enriched structure-activity relationship may pave the way for the further rational development of imidazole-containing derivatives as anti-tubercular agents.
结核病仍然是全世界人类已知的最常见、可传播且致死率最高的疾病之一。近年来，结核分枝杆菌的耐药性有加剧全球结核病流行之势，引发了广泛关注。为克服耐药性，开发具有新型作用机制的新药至关重要。含咪唑衍生物具有多种生物学特性，其中一些表现出优异的抗结核活性。最具代表性的例子是，4-硝基咪唑类药物地拉马尼已获批用于治疗耐多药结核病感染患者。因此，含咪唑衍生物在新型抗结核药物研发中备受关注。众多含咪唑衍生物被合成并筛选其对药物敏感和耐药结核分枝杆菌病原体的体内外抗分枝杆菌活性。本综述旨在概述含咪唑衍生物作为抗结核药物的最新研究进展，并总结这些衍生物的构效关系。丰富的构效关系可为含咪唑衍生物作为抗结核药物的进一步合理开发铺平道路。
