Abstract
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•A series of fourteen 5-benzoyl-4-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-2-one derivatives were synthesized.•Compounds were characterized and in-vitro screened against wild HIV-1 RT enzyme.•Cytotoxicity of all compounds were evaluated.•Putative binding modes of best active (A11) and least active (A4) compounds with wild HIV-1 RT were investigated.
In the present study, a series of fourteen 5-benzoyl-4-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-2-one derivatives were designed, synthesized and characterized by appropriate spectral analysis. Further, titled compounds were in-vitro screened against wild HIV-1 RT enzyme using ELISA based colorimetric assay, in which four compounds significantly inhibited the RT activity with IC50≤25µM. Moreover, two significantly active compounds of the series, A10 and A11 exhibited IC50 values 8.62 and 6.87µM respectively, during the in-vitro assay. Structure Activity Relationship (SAR) studies were performed for the synthesized compounds in order to estimate the effect of substitution pattern on the RT inhibitory potency. The cytotoxicity of the synthesized compounds was evaluated against T lymphocytes. Further, putative binding modes of the significantly active (A11) and the least active (A4) compounds with wild HIV-1 RT were also investigated using docking studies.