Molecular docking of Carica papaya leaves as antihypertensive at ACE and angiotensin II receptor

Angiotensin Converting Enzyme (ACE) inhibitor and Angiotensin II Reseptor Blocker (ARB) are a treatment mechanism for patients with hypertension. Papaya leaves have been proven to have the potential to lower blood pressure in hypertensive rat models through the mechanism of ACE inhibition. However, this study has not yet identified the active compounds that act as antihypertensive agents or predicted their safety. This study aims to predict the mechanisms of action of the active compounds in papaya leaves as antihypertensive agents through ACE and Angiotensin II Receptor Type 1 (AT1R) inhibition in silico, and to determine the potential for their development as oral drugs and their safety. The study uses computational design with 3D structures of the target proteins ACE and AT1R downloaded from the Protein Data Bank (PDB). The ligands, which are active compounds from Carica papaya leaves, were obtained from literature, and their 3D structures were downloaded from PubChem. The docking process was carried out using AutoDock Tools. Physicochemical predictions and pharmacokinetics predictions were conducted using the SwissADME and pkCSM websites. The indicators used for the affinity of active compounds are free energy and structural similarity of ligands compared to the drugs control. Solubility and pharmacokinetics follow the 5 criteria of Lipinski's rule, and the values for absorption, distribution, metabolism, and excretion, as well as hepatotoxicity or IC50. The docking results on the ACE protein indicate that the active compounds rutin, luteolin, epicatechin, and caffeic acid have free binding energy values below ΔG -7 kcal/mol. Meanwhile, on the AT1R protein, the active compounds carpaine and rutin show free binding energy values closest to ΔG -7 kcal/mol. Caffeic acid, Carpaine, Epicatechin, and Luteolin have good solubility and meet the 5 criteria of Lipinski's rule.The active compound carpaine has potential on both ACE and AT1R target proteins but exhibits weaker affinity compared to the control drug.