标题：Design, synthesis, and biologic evaluation of novel galloyl derivatives as HIV-1 RNase H inhibitors
作者：Gao, Ping; Wang, Xueshun; Sun, Lin; Cheng, Xiqiang; Poongavanam, Vasanthanathan; Kongsted, Jacob; Alvarez, Mar; Luczkowiak, Joanna; Pa 更多 作者机构：[Gao, Ping; Wang, Xueshun; Sun, Lin; Cheng, Xiqiang; Liu, Xinyong; Zhan, Peng] Shandong Univ, Sch Pharmaceut Sci, Dept Med Chem, Key Lab Chem Biol,Min 更多
通讯作者：Liu, XY;Zhan, P;MenendezArias, L;MenendezArias, L
通讯作者地址：[Liu, XY; Zhan, P]Shandong Univ, Sch Pharmaceut Sci, Dept Med Chem, Key Lab Chem Biol,Minist Educ, Jinan, Shandong, Peoples R China;[MenendezArias, L] 更多
来源：CHEMICAL BIOLOGY & DRUG DESIGN
关键词：galloyl derivatives; HIV-1; RNase H inhibitors
摘要：Human immunodeficiency virus (HIV) reverse transcriptase (RT)-associated ribonuclease H (RNase H) remains as the only enzyme encoded within the viral genome not targeted by current antiviral drugs. In this work, we report the design, synthesis, and biologic evaluation of a novel series of galloyl derivatives with HIV-1 RNase H inhibitory activity. Most of them showed IC(50)s at sub- to low-micromolar concentrations in enzymatic assays. The most potent compound was II-25 that showed an IC50 of 0.72 +/- 0.07 mu M in RNase H inhibition assays carried out with the HIV-1(BH10) RT. II-25 was 2.8 times more potent than beta-thujaplicinol in these assays. Interestingly, II-25 and other galloyl derivatives were also found to inhibit the HIV IN strand transfer activity in vitro. Structure-activity relationships (SAR) studies and molecular modeling analysis predict key interactions with RT residues His539 and Arg557, while providing helpful insight for further optimization of selected compounds.