Metabolites Isolated from Senecio nutans Sch. Bip and Their Synthesized Oximes Inhibit Angiotensin I-Converting Enzyme Activity in Vascular Smooth Muscle

Angiotensin-Converting Enzyme (ACE) plays a pivotal role in the renin-angiotensin system, modulating blood pressure and electrolyte homeostasis by deactivating bradykinin and activating angiotensin II. Metabolites from <i>Senecio nutans</i> (<b>1</b> and <b>3</b>), a plant indigenous to the Andean region of the Atacama Desert, and their respective oximes, <b>2</b> and <b>4</b>, were subjected to molecular docking analysis, employing six ACE crystal structures. ACE activity assays revealed that oximes exhibited superior inhibitory effects compared to metabolites. Among the compounds investigated, <b>2</b> emerged as the most potent ACE inhibitor (<b>2</b> = 11.5 μM and <b>4</b> = 13.4 μM). The vascular contractile response to Angiotensin I showed significant (<i>p</i> < 0.05) reductions in Ang I contraction with <b>2</b>, <b>3</b>, and <b>4</b> (97 ± 6%, 81 ± 6%, 81 ± 3% compared to control), while <b>1</b> exhibited no such effect. These results reinforce the potential of <b>2</b> as a promising ACE inhibitor and highlight its impact on vascular contractility. As such, it is a promising candidate for ACE inhibition and hypertension treatment.