药学学报, 2019, 54(8): 1392-1401
引用本文:
康家雄, 朱江, 李爱秀, 靳玉瑞. 化学合成类HIV整合酶和核糖核酸酶H双靶点抑制剂的研究进展[J]. 药学学报, 2019, 54(8): 1392-1401.
KANG Jia-xiong, ZHU Jiang, LI Ai-xiu, JIN Yu-rui. Advances in chemical synthesis of dual inhibitors of HIV integrase and ribonuclease H[J]. Acta Pharmaceutica Sinica, 2019, 54(8): 1392-1401.

化学合成类HIV整合酶和核糖核酸酶H双靶点抑制剂的研究进展
康家雄1,2, 朱江2, 李爱秀1,3, 靳玉瑞1
1. 中国人民武装警察部队武警后勤学院基础部药物设计实验室, 天津 300309;
2. 中国人民武装警察部队武警后勤学院卫生勤务系, 天津 300309;
3. 天津市职业与环境危害防制重点实验室, 天津 300309
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。
关键词:    人类免疫缺陷病毒      整合酶      核糖核酸酶H      双靶点抑制剂     
Advances in chemical synthesis of dual inhibitors of HIV integrase and ribonuclease H
KANG Jia-xiong1,2, ZHU Jiang2, LI Ai-xiu1,3, JIN Yu-rui1
1. Drug Design Laboratory of the Basic Courses Department, Logistics University of PAP, Tianjin 300309, China;
2. Department of Health Service, Logistics University of PAP, Tianjin 300309, China;
3. Tianjin Key Laboratory for Biomarkers of Occupational and Environmental Hazard, Tianjin 300309, China
Abstract:
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.
Key words:    human immunodeficiency virus    integrase    ribonuclease H    dual inhibitors   
收稿日期: 2019-04-22
DOI: 10.16438/j.0513-4870.2019-0295
基金项目: 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.
通讯作者: 李爱秀,Tel:86-22-84876331,E-mail:liaixiu2006@126.com
Email: liaixiu2006@126.com
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