In silico Molecular Docking and Identification of Bioactive Constituents from Unripe Carica papaya Fruit as Inhibitors of Angiotensin-Converting Enzyme (ACE)

Abstract

Hypertension is a major risk factor for renal and cardiovascular diseases, and angiotensin-converting enzyme (ACE) inhibitors are among the principal therapeutic agents used in its management. This study aimed to predict the ACE-inhibitory activity of unripe C. papaya fruit extract using an in silico approach. GC–MS analysis of the unripe fruit extract indicated the presence of multiple bioactive compounds. Structure-data files for the identified compounds, the standard inhibitor captopril, and ACE complexed with captopril were obtained from PubChem and the Protein Data Bank. The ligand files were converted to PDBQT format for docking. The docking analysis showed binding affinities ranging from −5.8 to −4.1 kcal/mol, while captopril and lisinopril had binding affinities of −5.5 and −7.7 kcal/mol, respectively. Six compounds—cyclooctaneacetic acid, 2-oxo; sucrose; 6,10,14-trimethyl-pentadecan-2-ol; 9,15-octadecadienoic acid, methyl ester, (Z,Z)-; 1-cyclohexylnonene; and [1,4]dioxino[2,3-b]-1,4-dioxin, hexahydro-2,3,6,7-tetramethyl—showed the strongest binding affinities. Similar to the standard drug, these compounds interacted with reported ACE active-site residues, including HIS383, HIS387, GLU384, and GLU411. Pharmacokinetic and toxicity properties were predicted using SwissADME and ProTox-II. The selected compounds showed favourable predicted pharmacological profiles and no predicted hepatotoxicity, immunotoxicity, cytotoxicity, carcinogenicity, or mutagenicity. These findings provide preliminary computational evidence that unripe C. papaya fruit contains constituents with potential ACE-binding activity.