Synthesis, in vitro anti-HIV-1 reverse transcriptase evaluation, molecular modelling, DFT analysis and acute oral toxicity assessment of benzotriazole derivatives.

In this study, we synthesized and assessed a series of benzotriazole derivatives (3–30) for their anti-human immunodeficiency virus (HIV)-1 reverse transcriptase (R.T.) activity and compared them to the standard drug efavirenz. Among these, compound 27 demonstrated noteworthy anti-HIV-1 R.T. activities. In vivo oral toxicity tests on the most potent compound, 27, indicating acceptable acute oral safety. We used molecular docking techniques to investigate the potential interactions between the synthesized compounds (ligands) and a target protein (PDB ID 1RT2) at the molecular level. Additionally, molecular dynamics studies were conducted on compound 27 within the active binding site of the co-crystallized HIV-1 RT structure (PDB ID 1RT2) to understand better the behaviour, interactions, and changes in biomolecular systems at the atomic or molecular scale over time. Finally, the DFT-derived HOMO and LUMO orbitals, along with an analysis of the molecular electrostatic potential map, provide insights into the reactivity characteristics of the molecule.