Virtual screening of Zanthoxylum acanthopodium DC. Fruit bioactive compounds as natural angiotensin-converting enzyme inhibitors

Abstract

The angiotensin-converting enzyme inhibitors (ACEi) is a widely prescribed anti-hypertensive drugs targeting the renin-angiotensin system (RAS). These drugs still have limitations due to their side effects. This study aims to identify the potential of bioactive compounds from Andaliman fruit (Zanthoxylum acanthopodium DC.) as natural ACEi for the treatment of hypertension with an in-silico approach. Phytoconstituents from Z. acanthopodium fruits were screened using the SwissADME web server for their bioavailability. The selected compounds were then paired to human ACE (PDB ID: 1O86) by site-specific docking to the ACE binding pocket. The stability of the interaction between ligand and protein was evaluated using molecular dynamics simulations in YASARA software. From a total of 39 compounds, we predict that 5 compounds namely kaempferol, quercetin, abscisic acid, benzophenone, and cis-3,5,3',4'-tetrahydroxystilbene can bind to ACE with good affinity and form interactions with key residues. The presence of these compounds may reduce the binding affinity of angiotensin I to ACE and alter the interaction site. Molecular dynamics simulations show the compounds have good interaction stability with ACE and remain in the active site until the end of the simulation. This study showed that five bioactive compounds from Andaliman fruit act potentially as natural ACE-inhibiting agents.