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Abstract
Hypertension remains a leading cause of cardiovascular morbidity, necessitating novel multitarget inhibitors. Imidazole derivatives exhibit diverse pharmacological activities, including potential modulation of vasoconstrictive pathways, yet few studies integrate computational
screening with synthetic validation for antihypertensive lead discovery. Four imidazole compounds were subjected to molecular docking using AutoDock Vina against
ACE (7bvq), AT1R (7ej8), ETAR (6ke5), and renin (5xpr) to predict binding affinities. The lead compound, 2-methyl-4,5-diphenyl-1H-imidazole, was synthesized via one-pot condensation of benzil, acetaldehyde, and ammonium acetate under reflux, followed by recrystallization. Physicochemical properties, ADMET parameters, and toxicity profiles were evaluated using SwissADME and Pro Tox 3 platforms. Docking revealed 2-methyl-4,5-diphenyl-1H-imidazole as the most potent ligand, with binding energies of -8.9 to -6.9 kcal/mol across all targets, driven by hydrophobic. It displayed high gastrointestinal absorption, blood-brain barrier permeability, balanced lipophilicity, and no
cardiotoxicity or nephrotoxicity. Synthesis yielded 57.36 % of pure yellowish crystals (m.p. 69- 71 °C). Other derivatives showed weaker binding, restricted distribution, or higher genotoxic risks. 2-Methyl-4,5-diphenyl-1H-imidazole is identified as a promising multitarget antihypertensive
lead with favorable drug-like properties and synthetic accessibility. It warrants further biological evaluation in enzyme inhibition, vasorelaxation, and in vivo models to advance toward clinical development.
screening with synthetic validation for antihypertensive lead discovery. Four imidazole compounds were subjected to molecular docking using AutoDock Vina against
ACE (7bvq), AT1R (7ej8), ETAR (6ke5), and renin (5xpr) to predict binding affinities. The lead compound, 2-methyl-4,5-diphenyl-1H-imidazole, was synthesized via one-pot condensation of benzil, acetaldehyde, and ammonium acetate under reflux, followed by recrystallization. Physicochemical properties, ADMET parameters, and toxicity profiles were evaluated using SwissADME and Pro Tox 3 platforms. Docking revealed 2-methyl-4,5-diphenyl-1H-imidazole as the most potent ligand, with binding energies of -8.9 to -6.9 kcal/mol across all targets, driven by hydrophobic. It displayed high gastrointestinal absorption, blood-brain barrier permeability, balanced lipophilicity, and no
cardiotoxicity or nephrotoxicity. Synthesis yielded 57.36 % of pure yellowish crystals (m.p. 69- 71 °C). Other derivatives showed weaker binding, restricted distribution, or higher genotoxic risks. 2-Methyl-4,5-diphenyl-1H-imidazole is identified as a promising multitarget antihypertensive
lead with favorable drug-like properties and synthetic accessibility. It warrants further biological evaluation in enzyme inhibition, vasorelaxation, and in vivo models to advance toward clinical development.
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