MOLECULAR DOCKING STUDY OF INDONESIAN PLANT-DERIVED BIOACTIVE COMPOUND TARGETING ESTROGEN RECEPTOR ALPHA (1L2J) IN CERVICAL CANCER

Abstract

Cervical cancer remains a leading cause of cancer-related mortality among women worldwide, with estrogen receptor alpha (ER-?) playing a key role in carcinogenesis. Although tamoxifen is an established ER-? antagonist, its clinical use is limited by drug resistance and tissue-specific adverse effects. Indonesian medicinal plants contain diverse phytochemicals with potential as alternative ER-? inhibitors. This study evaluated the binding affinities and molecular interaction profiles of six Indonesian plant-derived bioactive compounds against the ER-? ligand-binding domain (PDB ID: 1L2J) using molecular docking in MOE 2015.10, with tamoxifen as the reference ligand. Docking validation by re-docking the native ligand produced an RMSD of 1.5487 Å, confirming the reliability of the protocol. Among the tested compounds, carissanol exhibited the strongest binding affinity (S-score: ?14.7293 kcal/mol), surpassing tamoxifen (?12.7112 kcal/mol), and formed a key hydrogen bond with Gln305, along with extensive hydrophobic interactions. Quercetin also demonstrated strong binding (?13.5099 kcal/mol), whereas piperidine showed the weakest affinity (?5.5143 kcal/mol). These findings suggest that carissanol from Carissa spinarum L. is a promising natural lead compound targeting ER-? and merits further in vitro and in vivo investigations. Keywords: Cervical cancer, Estrogen Receptor Alpha, Molecular Docking, Carissanol, 1L2J