Anti-hypertensive properties of 2-[N-(4-methylbenzenesulfonyl)-1-phenylformamido]-n-(4-nitrophenyl)-3-phenylpropenamide: Experimental and theoretical studies

Abstract

Experimental and theoretical investigation of the anti-hypertensive activity of novel 2-[N-(4-methylbenzenesulfonyl)-1-phenylformamido]-N-(4-nitrophenyl)-3-phenylpropenamide (MBPNPP) was carried out. The experimental approach followed the dietary induction of spontaneously hypertensive adult male Wistar rats (SHRs) using 66% w/v d-fructose and the angiotensin I-converting enzyme (ACE) inhibitory activity assay while the theoretical study was achieved using DFT calculations and molecular docking against hypertension responsive proteins. The Becke-3-Paramater-Lee-Yang-Parr (B3LYP) functional/6–311G++(d,p) basis set was adopted. The molecular electronic properties such as the highest occupied molecular orbital (HOMO), the lowest unoccupied molecular orbital (LUMO) and other chemical reactivity parameters were evaluated to bring to light, the reactivity and stabilization mechanisms of MBPNPP. The highest daily oral dose of MBPNPP (10 mg/kg) significantly prevented increase in systolic blood pressure (SBP) comparable to positive and normal control groups receiving captopril (10 mg/kg/day) and distilled water (5 ml/kg) ad libitum respectively from 167.23 (negative control) to 124.50 and 120.17 (positive control). Molecular simulation was also carried out with target proteins; 2ydm, 2 × 8Y, and 3ZQZ, and the theoretical data expresses a much plausible therapeutic significance towards the control of hypertension. The frontier orbital energy gap of 3.066 eV was an indicator that the charge transfer interaction occurred within the molecule and indicates high chemical reactivity. Relative to the reference drug, Spironolactone, the compound under study showed a significant binding affinity of -9.0 kcal/mol, -8.3 kcal/mol, and -7.9 kcal/mol with the target proteins and better protein-ligand hydrogen bond interactions. The data gathered from the experimental and theoretical analysis including the docking scores showed excellent anti-hypertensive activity by MBPNPP.