Molecular Docking Of Bioactive Compounds From Mangosteen Peel (Garcinia Mangostana L.) And Design Of New Quercetin Derivatives As MAO-A Inhibitors For Anti-Stress Potential

Abstract

Stress is associated with an imbalance of neurotransmitters in the central nervous system. Monoamine Oxidase A (MAO-A) plays a role in the metabolism of monoamine neurotransmitters and therefore, has potential as a target for the development of anti-stress agents. Mangosteen peel (Garcinia mangostana L.) contains various bioactive compounds with potential for development as anti-stress agent candidates. This study aimed to analyze the interactions of bioactive compounds from mangosteen peel with MAO-A through molecular docking and to evaluate drug-likeness, ADME, toxicity, and structural modification of the selected compound. An in silico study was conducted on 70 bioactive compounds using PyRx-AutoDock Vina with MAO-A (PDB ID: 2Z5X). Validation was performed by redocking the native ligand Harmine. The selected compounds were subsequently analyzed using SwissADME, pkCSM, and Toxtree. Redocking of Harmine produced an RMSD of 1.581 Å and a binding affinity of −8.2 kcal/mol, indicating that the method was valid. The four best-performing compounds were Quercetin, Apigenin, Smeathxanthone A, and Epicatechin, with binding affinity of −9.0, −8.9, −8.6, and −7.4 kcal/mol, respectively. Quercetin was selected based on its lowest binding affinity and similarity of amino acid residue interactions with the native ligand. Modification of Quercetin produced (Z)-4-(prop-1-en-1-yl)-3,6-dihydro-[1,1'-biphenyl]-2,3',4'-triol with a binding affinity of −8.7 kcal/mol and an RMSD of 1.321 Å, accompanied by an improved ADME profile and low toxicity. The modified compound has potential for further development as an anti-stress agent candidate targeting MAO-A, however, further in vitro and in vivo studies are required.