Synthesis and study of anti-HIV-1 RT activity of 5-benzoyl-4-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-2-one derivatives

• Main Authors: Chander, S., Tang, C. R., Al Maqtari, H. M., Jamalis, J., Penta, A., Hadda, T. B., Sirat, H. M., Zheng, Y. T., Sankaranarayanan, M.
• Format: Article
• Published: Academic Press Inc. 2017
• Subjects: QD Chemistry
• Online Access: http://eprints.utm.my/id/eprint/75438/; https://dx.doi.org/10.1016/j.bioorg.2017.03.013

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 ≤ 25 µM. Moreover, two significantly active compounds of the series, A10 and A11 exhibited IC50 values 8.62 and 6.87 µM 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.