In-silico design of new enalapril analogs (ACE inhibitors) using QSAR and molecular docking models

Abstract

Angiotensin-converting-enzyme inhibitors (ACEI) are a group of drugs primarily used in the treatment of cardiovascular disease. In this study, MLR and PLS QSAR models were developed to evaluate the antihypertensive activity of new enalapril analogs, while binding affinities between each analog and ACE were determined with AutoDock. Consequently, analogs presenting para and meta trifluoromethyl substitutions, and a N,N-dialkyl aliphatic amide were the most promising analogs, exhibiting an IC50 of 0.009 nM and affinity energies of −8.9 kcal/mol, surpassing those of enalapril. Furthermore, all promising analogs were predicted to be less toxic than enalapril according to the software PreADMET.

Keywords

• IECA
• QSAR
• Docking
• IC50
• MLR
• PLS