近年来结核分枝杆菌外排泵抑制剂研究进展  

Research progress on efflux pump inhibitors of Mycobacterium tuberculosis in recent years

作　　者：郑承鸿 王明华[1] 王菊仙[1] ZHENG Cheng-hong;WANG Ming-hua;WANG Ju-xian(Institute of Medical Biotechnology,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100050,China)

机构地区：[1]中国医学科学院,北京协和医学院,医药生物技术研究所,北京100050

出　　处：《药学学报》2023年第10期2995-3003,共9页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(3214003)。

摘　　要：目前,一线抗结核药物的耐药问题使得对结核病的防治日益困难,这对全球公共卫生造成了严重威胁。研究表明,外排泵是导致细菌产生多药耐药和广泛耐药的重要原因之一,而外排泵抑制剂可以抑制细菌外排抗菌药物,从而降低细菌耐药性。目前有大量天然产物和化学合成物质被报道具有外排泵抑制活性,但因毒性和药代动力学性质等原因至今未运用于临床。因此,本文对近年来报道的结核分枝杆菌外排泵抑制剂的外排泵抑制活性、抗菌活性以及构效关系进行了总结,为研发活性更好、毒性更小的新型外排泵抑制剂提供参考。Currently,the resistance of first-line anti-tuberculosis drugs has made the prevention and treatment of tuberculosis increasingly difficult,posing a serious threat to global public health.Several studies have shown that efflux pumps are one of the important causes for bacteria to develop multi-drug resistance and extremely-drug resistance,and efflux pump inhibitors can inhibit the efflux of antibacterial drugs,thereby reducing bacterial drug resistance.Numerous natural products and synthetic compounds have been reported to possess efflux pump inhibitory activity,but they have not been applied in clinical settings because of their toxicity,pharmacokinetic properties,etc.Therefore,we summarized the efflux pump inhibitory activity,antimicrobial activity,and structure-activity relationships of reported efflux pump inhibitors against Mycobacterium tuberculosis in recent years,providing references for the development of new efflux pump inhibitors with better activity and lower toxicity.

关 键 词：细菌耐药 结核分枝杆菌 外排泵 外排泵抑制剂 抗菌活性 构效关系 

分 类 号：R914[医药卫生—药物化学]