Abstract
Hypertension is a significant health concern globally, necessitating the exploration of novel therapeutic agents. This study aimed to computationally screen imidazole derivatives for potential antihypertensive activity and assess their pharmacokinetic and toxicity profiles. Molecular docking simulations were employed to evaluate the binding affinities of imidazole compounds towards hypertension-related receptor targets, namely angiotensin-converting enzyme (ACE) and angiotensin II receptor (AT1R).
Molecular docking simulations were employed to assess the binding affinities of 20 imidazole ligands towards ACE and AT1R. Subsequently, ADMET properties were evaluated to gauge the pharmacokinetic profiles of the identified compounds. Toxicity profiling using ProTox-3.0 software provided insight into the safety profiles of these imidazole ligands. Tanimoto coefficient analysis with ChemAxon’s Marvin suite compared these compounds with established antihypertensive drugs, serving as a benchmark for safety and efficacy assessment.
Among the twenty imidazole compounds, 1-ethyl-2-methylbenzimidazole, 5-methyl-2-nitro-1H-imidazole, 4,5-diphenyl-1H-imidazole, and 5-phenyl-1H-imidazole showed promising binding affinities towards ACE and AT1R. These compounds exhibited favorable pharmacokinetic profiles, indicating their potential suitability for further development as antihypertensive agents. However, toxicity profiling revealed a moderate level of drug toxicity for the identified imidazole ligands. Tanimoto coefficient analysis comparing the structural and hence the functional similarities of these imidazole derivatives with the standards and their potential as viable treatment options for hypertension showed a moderate similarity.
The identified imidazole compounds hold promise as potential antihypertensive agents, as evidenced by their strong binding affinities towards hypertension-related receptor targets and favorable pharmacokinetic profiles. Despite the moderate level of drug toxicity observed, the relative safety and efficacy of these compounds compared to established antihypertensive drugs suggest their potential utility in hypertension management. However, further experimental modification, optimization, and validation are necessary to confirm their efficacy and safety in vivo.
