Integrated approach for studying anti-angiotensin converting enzyme activity of triazole derivatives to down-regulate diabetes

Abstract

The effects of triazole and its derivatives as anti-angiotensin converting enzyme activity were investigated using combined computational approach. This work is directed at examining the anti-angiotensin converting enzyme activity of the studied triazole derivatives via density functional theory and molecular modeling studies using in silico approach. This work was executed using Spartan 14 for optimization. The downloaded receptor (human angiotensin-converting enzyme (PDB ID: 3NXQ)) from protein data bank by removing water molecules and other small molecules downloaded with the target before subjecting it to docking calculation and molecular dynamic simulation studies. In this work, we discovered that addition of methyl and 2-ethyl-1H-indole to triazole as parent compound enhanced the activity of compound 4 and this was revealed via the predicted highest occupied molecular orbital (HOMO) (-4.53 eV) and energy gap (3.73 eV). More so, Compound 4 with -10.5 kcal/mol possess the highest strength to impede human angiotensin-converting enzyme (PDB ID: 3NXQ) than other investigated compound and the metformin. The developed quantitative structure activity relationship (QSAR) with squared correlation coefficient (R²) of 0.745234 and adjusted R² of 0.617852 proved to be valid and predictable which was confirmed via the predicted percentage inhibiting concentration (%IC₅₀). The molecular dynamic simulation and pharmacokinetic studies of the compound ((Compound 4) and the reference drug (metformin)) that possess the highest binding affinity were investigated and reported. These findings may give insight into developing library of drug-like triazole-based compounds as proficient anti-diabetic agents.