Molecular modeling of plant flavonoids as angiotensin converting enzyme (ACE) inhibitors in hypertension: A docking study

Abstract

Hypertension is one of the most common worldwide diseases that results in the progression of several cardiovascular disorders and stroke. Angiotensin converting enzyme (ACE) has become a major target control for hypertension. Several synthetic ACE inhibitors such as captopril, lisinopril, enalapril etc. are in clinical use but are found to have certain side effects and drug-drug interactions. Therefore, there is a great need to search for more economical, nontoxic and safer inhibitors. Flavonoids, the polyphenolic compounds in plants have been reported for some inhibitory effects against ACE. We conducted a molecular docking study on flavonoid derivatives; flavones, flavonols, flavanones and flavan-3-ols with two angiotensin converting enzymes in complex with synthetic drugs, captopril and lisinopril respectively by ArgusLab 4.0.1 software. The aim of this study is to investigate the binding modes of flavonoid derivatives with ACE to design more safer natural drugs as alternatives to synthetic drugs. The results showed the best binding affinity of ACE with that of Apigenin, a flavone having the lowest binding energy of -8.45kcal/mol in ACE- captopril complex and -8.33 kcal/mol with that of lisinopril complex. This information can be utilized to design potent therapeutic drugs from natural plant flavonoids in the regulation of blood pressure.