Abstract
Inspired by our previous studies to discover novel human immunodeficiency virus-1(HIV-1)non-nucleoside reverse transcriptase inhibitors(NNRTIs)by targeting the tolerant region Ⅱ of the NNRTIs binding pocket(NNIBP),a series of novel benzo[4,5]thieno[2,3-d]pyrimidine derivatives were designed through structure-based drug design as novel potent HIV-1 NNRTIs.The results showed that compound 16b was the most active inhibitor,exhibiting 50％effective concentration(EC50)values from 0.021 μmol/L to 0.298 μmol/L against wild-type(WT)and a panel of NNRTIs-resistant HIV-1 strains.Moreover,16b was demonstrated with a significantly low 50％cytotoxicity concentration(CC50)value(＞200μmol/L)and high selectivity index(SI)values.In addition,16b yielded moderate reverse transcriptase(RT)enzyme inhibi-tion with a 50％inhibition concentration(IC50)value of 0.183 μmol/L,which demonstrated that it acted as HIV-1 NNRTIs.The binding mode of 16b with RT was also illustrated via molecular docking.Overall,this work provided a novel lead compound for developing potent HIV-1 NNRTIs.
基金项目
National Natural Science Foundation of China(NSFC)(81973181)
National Natural Science Foundation of China(NSFC)(82273773)
Shandong Provincial Natural Science Foundation(ZR2020YQ61)
Shandong Provincial Natural Science Foundation(ZR2020JQ31)
Qilu Young Scholars Program of Shandong University and Taishan Scholar Program at Shandong Province()
NETL
NSTL
万方数据