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
出版年:2019
卷:93
期:4
页码:582-589
DOI:10.1111/cbdd.13455
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.
收录类别:SCOPUS;SCIE
资源类型:期刊论文
原文链接:https://www.scopus.com/inward/record.uri?eid=2-s2.0-85060617101&doi=10.1111%2fcbdd.13455&partnerID=40&md5=1aaef8ffd10e67e40c92df55a070e02c
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