Design, synthesis and activity evaluation of novel pyridinone derivatives as anti-HIV-1 dual(RT/IN) inhibitors  

新型吡啶酮类HIV-1双靶点(RT/IN)抑制剂的设计、合成及生物活性评估（英文）

作　　者：Quanzhi Yang Tao Sheng Ningning Fan Yameng Hao Yuanyuan Cao Ying Guo Zhili Zhang Chao Tian Junyi Liu Xiaowei Wang 杨全志;盛涛;樊宁宁;郝亚萌;曹源源;郭莹;张志丽;田超;刘俊义;王孝伟(北京大学医学部药学院化学生物学系,北京100191)

机构地区：Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China

出　　处：《Journal of Chinese Pharmaceutical Sciences》2017年第1期31-44,共14页中国药学（英文版）

基　　金：National Natural Science Foundation of China(Grant No.21172014,812111023 and 81172733);grants from the Ministry of Science and Technology of China(Grant No.200 9ZX09301-010)

摘　　要：Three series of novel anti-immunodeficiency virus 1 （HIV-1） dual （RT/1N） inhibitors were rationally designed by introducing a functioning diketo acid （DKA） into pyridin-2-one scaffold. To efficiently analyze inhibitory activity, these compounds were screened against HIV-1 RT and IN respectively via surface plasmon resonance （SPR）, and active compounds were subsequently evaluated by enzyme assay. It was noteworthy that compound A2 exhibited moderate activity against both HIV-1 RT and IN. This result provided information for further development of pyridinone analogues as potent dual HIV-1 inhibitors.本文以吡啶酮类逆转录酶抑制剂和二酮酸类(DKA)整合酶抑制剂为先导化合物,选取必要的药效团进行高度整合并对其进行合理优化,设计出的三个系列的HIV-1 RT/IN双靶点抑制剂。采用表面等离子共振(SPR)技术及酶联免疫吸附法对目标化合物分别进行了体外抗HIV-1 RT和IN的生物活性测定。实验结果表明,化合物A2对逆转录酶和整合酶都表现出较好的抑制活性,为深入研究该类化合物作为HIV-1双靶点抑制剂提供了相关信息。

关 键 词：Pyridinone derivatives HIV-1 dual inhibitor Reverse transcriptase INTEGRASE 

分 类 号：R91[医药卫生—药学] R914.5