Design, Synthesis and Evaluation of Some Novel 1-phenyl-3-(5-phenyl-1H-imidazol-1-yl) Thiourea Derivatives as Anti-HIV Agents.

Abstract

Objective: In the present study, a series of nineteen compound of 1-phenyl-3-(5-phenyl1H-imidazol-1-yl) thiourea derivatives (5a-9b) were designed, synthesized, characterized by physicochemical and spectral data (IR, 1H NMR, and mass spectroscopy) and evaluated for their Anti-HIV activity with the aim to develop novel substituted imidazole derivatives with broad-spectrum chemotherapeutic properties.Methods: Compounds (5a-9b) were designed by using Glide 5.0 to carry out binding mode analysis of N-substituted imidazoles against reverse transcriptase enzyme of wild type as well as resistant strains of HIV-1 virus with PDB ID: 1RT2, synthesized by reacting various substituted anilines and substituted phenacyl bromides in four steps and evaluated their anti HIV activity as well as cytotoxicity assay through MTT colorimetric measure.Results: Compounds 6a, 6b, 6c, 6d, 7c, 9a and 9b being the most active exhibited therapeutic index that were >22.4, 31.1, 30.5, 51.5, 34.6, 30.5 and 85.6 compared to Zidovudine (AZT) having therapeutic index (TI) 514342.6. Compound 9b showed the highest docking score -12.47 in the active site of the HIV protein of 1RT2 as well better in vitro anti-HIV activity.

Keywords: Molecular docking; Imidazole derivatives; Reverse transcription; Non-nucleoside; reverse transcriptase inhibitors (NNRTI); Anti-HIV