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Discovery of potent HIV-1 non-nucleoside reverse transcriptase inhibitors by exploring the structure-activity relationship of solvent-exposed regions I

Tijdschriftbijdrage - Tijdschriftartikel

Two novel series of human immunodeficiency virus-1 (HIV-1) non-nucleoside reverse transcriptase inhibitors (NNRTIs) bearing a thiophene[3,2-d]pyrimidine scaffold and sulfonamide linker in the right wing have been identified, which demonstrated activity against the wild-type (WT) HIV-1 strain in MT-4 cells with inhibitory concentrations ranging from micromolar to submicromolar. Especially, against the mutant strains K103N and E138K, most compounds exhibited more potent activity than against WT HIV-1. Compound 7 (EC50  = 0.014, 0.031 μM) achieved the most potent activity against the two mutants, being more effective than that of nevirapine (NVP, EC50  = 7.572, 0.190 μM) and comparable to that of etravirine (ETV, EC50  = 0.004, 0.014 μM). Molecular docking experiments on the novel analogs have also suggested that the extensive network of main chain hydrogen bonds are important in the binding mode, which may provide valuable insights for further optimization.
Tijdschrift: Chemical Biology & Drug Design
ISSN: 1747-0277
Issue: 4
Volume: 93
Pagina's: 430 - 437
Aantal pagina's: 8
Jaar van publicatie:2019
Trefwoorden:Biochemie & -fysica en Moleculaire biologie, Organische en medische scheikunde