EFFECT OF HOMOPTEROCARPIN, A BIOFLAVONOID FROM AFRICAN TEAK(Pterocarpus erinaceous) ON ANGIOTENSIN- CONVERTING ENZYMEACTIVITY

Abstract

Hypertension results to cardiovascular mortalitydue to side effects of synthetic drugs used in prolonged arrangement with synthetic drugs, therefore the use of plants for medicine is gainingmore acceptability worldwide due to its availability, affordability, efficiency and considerable safety. This study was designed to evaluate the inhibitory potentials and kinetics of homopterocarpin on Angiotensin-1-Converting Enzyme (ACE1) activity. In addition, the molecular dynamics involved in the inhibition in silico was studied. The sensitivity and inhibition of ACE1 by homopterocarpin using N-[3-(2-furyl)-acryloyl]-Phe-Gly-Gly (FAPGG) as enzyme substrate was evaluated by Michealis Menten’s approach. The kinetics was determined from Lineweaver–Burk model and IC50 was calculated. In addition,Ki, Vmax, and Km were estimated. Dissociation constant (Kd) was also calculated using Cheng-prusoff’s empirical analysis as well as catalytic efficiency, hills coefficient. Homopterocarpin was use as ligand for molecular interaction whereby lisinopril, a known ACE1 inhibitor was taken as standard comparative analysis. Computational docking analysis was performed using Autodock vina option based on Kcal/mol. Homopterocarpinsignificantly inhibited ACE1 with an IC50 of 170 μg/ml and enzyme kinetic analysis proved that homopterocarpin is non-competitive inhibitors of ACE1with Michaelis Menten constant (Km) which was calculated to be 0.2 μg/ml and a maximum rate of substrate hydrolysis (Vmax) was obtained to be 0.01, 0.009 and 0.06 μg/ml. The inhibitory constant (Ki) was estimated to be 0.19 and dissociation constant (Kd) were calculated to be 5.96, 5.26 and 4.47μg/ml, also the catalytic efficiency (CE) was obtained to be 0.05, 0.045, 0.03. Cooperativity was calculated to be 1.903 using Hill coefficient (nH) indicating positive cooperativity of the inhibition. The molecular docking studies revealed optimum binding energy of homopterocarpin with ACE1 as energy of -7.8kcal as compared to standard -8.6kcal. Molecular docking studies also confirmed that homopterocarpin inhibited ACE1 via interaction with 8 amino acids at the active site and this interaction was stabilized by hydrogen and hydrophobic bonds. The study also showed that homopterocarpin displaced Zn2+ at active site of the enzyme in a manner similar to lisinopril.The study revealed the ACE1 inhibitory potential of homopterocarpin and the mechanism behind its antihypertensive potential. Therefore, homopterocarpin couldbe considered as one of the potential ACE1 inhibitor.