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Description
Abstract:
Benzotriazole, a pharmaceutically and medicinally important heterocyclic scaffold, is known for its wider pharmacological potentials, including but not limited to antimicrobial, anti-cancer, and antifungal, etc. activities. We herein established anti-HIV-1 (the non-nucleoside reverse transcriptase inhibitors (NNRTIs) activities for a set of newly designed benzotriazoles using computational methodologies (i.e., molecular docking, Normal mode analysis, etc.). A series of 7 designed compounds (4a-4h) were drawn using ‘ChemDraw’ Professional 15.0 and ‘MM2; the energy was minimized. The binding interactions of docked compounds were visualized using ‘PyMOL. A series of designed benzotriazole (4a-4h) derivatives were docked against non-nucleoside inhibitory binding pocket (NNIBP) of HIV-1 RT (PDB ID:1RT2) receptor using Auto-dock Vina software. Binding mode results showed that among eight designed compounds, compound-4a {1-(4-chlorophenyl)-2-(perbromo-2H-benzo[d][1,2,3]triazol-2-yl)ethan-1-ol} gave the highest docking score of -9.3 Kcal/mol; when compared to the standard Nevirapine (-7.2 Kcal/mol). Binding mode analysis also exhibited hydrogen bond interactions with PRO-236 and LYS-103 amino acids of the NNIBP of 1RT2. Moreover, we also analyzed theoretically pharmacokinetics of designed molecules, which also resulted in promising ADMET profiles. The NMA calculations carried out for the best docked: protein complexes using the ‘iMODS’ server retained relatively good deformability in them (Lower eigenvalue profile). Altogether, NMA results depicted an acceptable range of values. It is therefore concluded that compound 4a; can be used as a lead for preparing further synthetic derivatives acting against HIV-1 targets.
Keywords: Benzotriazole, NNRTIs, NNIBP, HIV-1 RT