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Design, synthesis, and biological evaluation of benzo[4,5]thieno[2,3-d]pyrimidine derivatives as novel HIV-1 NNRTIs
- Source :
- Chinese Chemical Letters; 20240101, Issue: Preprints
- Publication Year :
- 2024
-
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 16bwas 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, 16bwas demonstrated with a significantly low 50% cytotoxicity concentration (CC50) value (>200 µmol/L) and high selectivity index (SI) values. In addition, 16byielded moderate reverse transcriptase (RT) enzyme inhibition 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 16bwith RT was also illustrated viamolecular docking. Overall, this work provided a novel lead compound for developing potent HIV-1 NNRTIs.
Details
- Language :
- English
- ISSN :
- 10018417
- Issue :
- Preprints
- Database :
- Supplemental Index
- Journal :
- Chinese Chemical Letters
- Publication Type :
- Periodical
- Accession number :
- ejs63618296
- Full Text :
- https://doi.org/10.1016/j.cclet.2023.108827