New oxadiazol-5-ones derivatives and their performance as angiotensin-converting enzyme (ACE) inhibitors

Abstract

Angiotensin-converting enzyme inhibitors are widely used in treating arterial hypertension, acting on the renin-angiotensin-aldosterone system and controlling blood pressure. We present a novel, greener, and faster methodology to assess the 1,2,4-oxadiazol-5-one ring and perform molecular modifications to obtain angiotensin-converting enzyme (ACE) inhibitors using this heterocyclic core. Molecular docking simulations indicate that the tested compounds exhibited an affinity for the ACE binding site, with scores comparable to the commercial inhibitor lisinopril. However, in vitro assays revealed that the compounds were ineffective in inhibiting ACE activity. The lack of inhibition may be related to the compounds' more apolar nature. These results emphasize the importance of integrating computational and experimental approaches in developing new drugs, providing valuable insights for planning future studies to optimize the activity of synthesized compounds.