Studi In Silico Molekuler Turunan Kumarin sebagai Kandidat Inhibitor ER-α pada Antikanker Payudara

Abstract

Cancer is one of the leading causes of death worldwide, prompting the development of new candidate therapeutic agents. Coumarin derivatives have potential anticancer activity, but their pharmacokinetic characteristics, toxicity, and binding affinity for the target receptor require evaluation. This study aims to evaluate the suitability of 11 coumarin derivatives as candidate anticancer agents based on Lipinski’s Rule of Five, absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles, and binding affinities predicted through molecular docking. The study was conducted in silico through compound screening, docking method validation, and analysis of interactions with the target receptor. Validation by redocking the native ligand to the 3ERT receptor structure yielded an RMSD value of 0.696 Å, supporting the method’s ability to reproduce the native ligand’s binding pose. Of the 11 compounds evaluated, 6 passed screening and underwent further analysis through molecular docking. The analysis showed that suberosin had the best predicted binding affinity among the compounds that passed screening, with an estimated binding free energy (ΔG) of −6.3707 kcal/mol and a predicted inhibition constant (Kᵢ) of 21.4175 μM. Based on the screening and molecular docking results, suberosin is the most promising coumarin derivative candidate among the compounds analyzed. These findings provide a computational basis for prioritizing suberosin for in vitro and in vivo testing as a candidate anticancer agent.