Molecular Docking Investigation of Muntingia calabura L. Bioactive Compounds as Estrogen Receptor-α (ER-α) Inhibitors for Anticancer Therapy

Abstract

Introduction — Cancer is one of the leading causes of death in the world and its development is related to genetic changes and dysregulation of cellular signaling pathways. Kersen leaves (Muntingia calabura L.) are known to contain various bioactive compounds that have the potential to be natural anticancer agents. This study aims to evaluate the anticancer potential of kersen leaf bioactive compounds against Estrogen Receptor-α (ER-α) receptors through an in silico approach.

Methods — The study was conducted using PASS Online for prediction of biological activity, SwissADME for drug-likeness evaluation based on Lipinski's Rule of Five, molecular docking using PyRx AutoDock against ER-α receptors, and ADMET analysis using PreADMET and Toxtree.

Results — A total of 11 bioactive compounds were successfully identified from Kersen leaves. The results of PASS Online showed that all compounds had potential anticancer activity with a higher Pa value than Pi. Drug-likeness tests showed 8 of the 11 compounds met the Lipinski criteria. The results of molecular docking showed that 3'-Hydroxydaidzein (MC9) had the best binding affinity to ER-α receptors with a binding affinity value of −8.7 kcal/mol, lower than N-acetylcysteine (−6.6 kcal/mol). ADMET analysis showed that MC9 had high intestinal absorption (93.604%), good permeability, and was neither carcinogenic nor mutagenic in nature.

Conclusions — The compound 3'-Hydroxydaidzein (MC9) has the potential to be a candidate for natural anticancer agents through ER-α receptor inhibition because it exhibits a strong binding affinity, meets drug-likeness criteria, and has a good pharmacokinetic and safety profile.