| Literature DB >> 29670703 |
Dongwei Kang1, Zhao Wang1, Heng Zhang1, Gaochan Wu1, Tong Zhao1, Zhongxia Zhou1, Zhipeng Huo1, Boshi Huang1, Da Feng1, Xiao Ding1, Jian Zhang1, Xiaofang Zuo1, Lanlan Jing1, Wei Luo1, Samuel Guma1, Dirk Daelemans2, Erik De Clercq2, Christophe Pannecouque2, Peng Zhan1, Xinyong Liu1.
Abstract
Based on the detailed analysis of the binding mode of diarylpyrimidines (DAPYs) with HIV-1 RT, we designed several subseries of novel NNRTIs, with the aim to probe biologically relevant chemical space of solvent-exposed tolerant regions in NNRTIs binding pocket (NNIBP). The most potent compound 21a exhibited significant activity against the whole viral panel, being about 1.5-2.6-fold (WT, EC50 = 2.44 nM; L100I, EC50 = 4.24 nM; Y181C, EC50 = 4.80 nM; F227L + V106A, EC50 = 17.8 nM) and 4-5-fold (K103N, EC50 = 1.03 nM; Y188L, EC50 = 7.16 nM; E138K, EC50 = 3.95 nM) more potent than the reference drug ETV. Furthermore, molecular simulation was conducted to understand the binding mode of interactions of these novel NNRTIs and to provide insights for the next optimization studies.Entities:
Year: 2018 PMID： 29670703 PMCID： PMC5900328 DOI： 10.1021/acsmedchemlett.8b00054
Source DB: PubMed Journal: ACS Med Chem Lett ISSN： 1948-5875 Impact factor: 4.345