喹啉杂合体的抗结核活性

Quinoline Hybrids with Anti-tubercular Potential

结核病主要由结核分枝杆菌引起,具有高发病率和死亡率等特点,是全球最具传染性的致命疾病之一。一线抗结核药物在结核患者的治疗中发挥着至关重要的作用,但结核分枝杆菌可通过内在性和获得性机制快速产生耐药性,降低了这些药物的疗效。因此,开发新型抗结核药物势在必行。喹啉类化合物可与结核分枝杆菌的多个作用靶点相结合,具有潜在的抗结核活性。喹啉母核可能是寻找新型抗结核药物的优秀骨架。特别值得一提的是,喹啉类抗结核药物贝达喹啉是继利福平之后50多年来首次问世的抗结核新药,2016年被中国国家食品药品监督管理总局批准用来联合治疗成人耐多药肺结核,这也是我国首次上市治疗耐多药肺结核新药。其中,喹啉杂合体可同时作用于结核分枝杆菌的多个结合靶点,对药敏型和耐药结核均显示出潜在的活性,引起了药物化学家的普遍关注。本文探讨了喹啉杂合体的抗结核活性及构—效关系,为进一步研究提供参考。

Tuberculosis(TB),caused predominately by Mycobacterium tuberculosis(MTB),is the most infectious lethal disease globally with high morbidity and mortality rates.The first-line anti-TB agents play a pivotal role in the treatment of TB patients,but the rapid development of drug-resistant strains through intrinsic and acquired mechanisms reduces their efficacy.Hence,it's urgent to develop novel anti-TB agents.Quinoline derivatives have the potential to have anti-TB activity since they may interact with a variety of MTB targets.It's worth to notice that the quinoline derivative bedaquiline,the first marketed anti-TB agent after rifampicin,has already been approved for the treatment of multidrug-resistant TB(MDR-TB),demonstrating that quinoline moiety is a useful skeleton for the development of novel anti-TB agents.In particular,quinoline hybrids may offer novel anti-TB drugs due to their potential to act on many sites in MTB strains and their activity against both drug-sensitive and drug-resistant MTB,which has attracted widespread attention from medicinal chemists.In this paper,the anti-TB potential and the structure-activity relationship of quinoline hybrids are discussed,which will provide a reference for further research.