Sustainable In Silico Discovery of Antihypertensive Agents from Papuan Red Fruit Compounds

Abstract

Hypertension remains a leading cause of cardiovascular morbidity and mortality worldwide, while the long-term use of angiotensin-converting enzyme inhibitors (ACEIs) is often associated with adverse effects, drug resistance, and high treatment costs, highlighting the need for safe and affordable natural alternatives. Pandanus conoideus (red fruit), an endemic Papuan plant rich in carotenoids, tocopherols, unsaturated fatty acids, and phenolic compounds, has demonstrated antioxidant and vasoprotective properties that may inhibit ACE activity. This study aimed to evaluate the ACE inhibitory potential of major carotenoids from P. conoideus using an in silico approach. Molecular docking and pharmacokinetic analyses were performed using BIOVIA Discovery Studio, AutoDockTools, and AutoDock Vina to prepare molecular structures, simulate ligand–receptor interactions, and visualize binding conformations. The results showed that ?-carotene, lutein, and capsanthin exhibited stronger binding affinities toward ACE (?8.4 to ?8.7 kcal/mol) than the reference drug captopril (?5.7 kcal/mol). Whereas captopril primarily formed hydrogen bonds with Arg522, carotenoids were stabilized mainly through hydrophobic and van der Waals interactions within the ACE catalytic pocket. Capsanthin demonstrated the most favorable binding configuration by forming additional hydrogen bonds with Phe102 and Gln120, suggesting greater binding stability. These findings indicate that carotenoids from Pandanus conoideus, particularly capsanthin, have promising potential as natural ACE inhibitors and warrant further in vitro and in vivo investigations to validate their antihypertensive efficacy and safety