摘要
尽管已有31种上市的单靶点抗HIV药物和高效抗逆转录病毒疗法用于AIDS的临床治疗,但寻找安全高效的新型抗HIV药物仍是全世界面临的一项严峻挑战。单组分多靶点药物具有降低耐药的可能性、简化给药剂量及提高患者服药顺从性等优点,现已成为抗HIV药物研发领域的热点。HIV整合酶(IN)和核糖核酸酶H (RNase H)均为病毒复制过程中的关键酶,是药物开发的重要靶标。近年来,通过合理药物设计和筛选途径,发现了多种结构类型的HIV IN和RNase H (IN/RNase H)双靶点抑制剂。本文主要对化学合成类HIV IN/RNase H双靶点抑制剂的研究进展进行介绍,以望对多靶点抗HIV药物的研发有所启示。
Antiretroviral therapy has been used for treating AIDS with 31 single-target anti-HIV drugs currently on market. Searching for safe and effective of novel anti-HIV drugs remains a challenge worldwide. Multi-targets single-structure compounds referred to as designed multiple ligands(DMLs) have become a hot topic of producing anti-HIV drugs recently due to reduction in the likelihood of drug resistance, simplified dosing and improved patient adherence. Integrase(IN) and ribonuclease H(RNase H) are two indispensable enzymes in HIV republication,therefore are two important targets for developing anti-HIV drugs. Recently, diverse dual inhibitors of HIV IN and RNase H(IN/RNase H) have been developed via rational drug design and screening. This review summarizes the advances in chemically synthesized dual inhibitors of HIV IN/RNase H to provide the information for developing multi-targets anti-HIV drugs.
作者
康家雄
朱江
李爱秀
靳玉瑞
KANG Jia-xiong;ZHU Jiang;LI Ai-xiu;JIN Yu-rui(Drug Design Laboratory of the Basic Courses Department,Logistics University of PAP, Tianjin 300309, China;Department of Health Service, Logistics University of PAP, Tianjin 300309, China;Tianjin Key Laboratory for Biomarkers of Occupational and Environmental Hazard, Tianjin 300309, China)
出处
《药学学报》
CAS
CSCD
北大核心
2019年第8期1392-1401,共10页
Acta Pharmaceutica Sinica
基金
国家自然科学基金项目(81241114,30472166)
天津市科技攻关计划重点科技攻关专项基金资助项目(06YFGZSH07000)
武警后勤学院研究生创新课题(WHYC201605)
武警后勤学院科研创新团队
