Bioinformatic analysis of some natural antihypertensive compounds from medicinal plants as promising inhibitory agents against Angiotensin-Converting Enzyme

Angiotensin Converting Enzyme (ACE) inhibition has been a promising avenue for anti-hypertensive drug development. Our study investigated the inhibitory potential of bioactive compounds derived from six medicinal plants (Allium sativum L., Zingiber officinale Roscoe, Acalypha godseffiana Mast., Moringa oleifera Lam., Vernonia amygdalina Delile, and Rauvolfia vomitoria Afzel.) against ACE using in silico methods. Thirty-one (31) bioactive compounds were screened while Ramipril, and Enalapril were employed as control drugs. 3D structures and canonical Simplified Molecular Input Line Entry System (SMILES) of the bioactive compounds and control drugs were obtained from the PubChem online server. Drug-likeness assessment of the bioactive compounds and protein-ligand docking of successful compounds were conducted using SwissADME online server and AutoDock Vina software. ADMET (absorption, distribution, metabolism, excretion, toxicity) analysis was also done to evaluate the suitability of the hit ligands for further drug development. Of the 31 compounds screened, 17 passed at least four of the five standard rules of drug-likeness determination, while the control drugs (Ramipril and Enalapril) failed one of the rules. Ajmaline, Apigenin, Quercetin, Cryptolepine, Luteolin, Hydroxyvernolide, Kaempferol and Vernodalol had higher binding energies of -9.6 kcal/mol, -8.7 kcal/mol, -8.5 kcal/mol, -8.4 kcal/mol, -8.4 kcal/mol, -8.3 kcal/mol, -8.3 kcal/mol and -7.8 kcal/mol, respectively than Ramipril and Enalapril (-7.6 kcal/mol, and -7.5 kcal/mol). The higher binding energies and the stability of their binding interactions denote these hit ligands as potential antihypertensive drugs targeting ACE. However, wet lab experimental investigation is necessary to validate the inhibitory activity of these compounds and elucidate their mechanisms of action.