ABSTRACT
One of the most common triggers of breast cancer is over-expression of estrogen receptor alpha (ERα). Long-termtherapy of tamoxifen, an ERα antagonist, can reduce patient’s quality of life because of its side effects. In the previousstudy, 2’,4’-dihydroxy-6-methoxy-3,5-dimethylchalcone (ChalcEA) was isolated as an active compound from theEugenia aquea leaves that is responsible for breast cancer treatment with positive ERα, however, the potency is lowerthan tamoxifen. The aim of this study is to find the best-modified chalcone that binds well with the ERα. Drug designapproaches used in this study were Structure-Based (Autodock 4.1) and Ligand-Based (LiganScout 4.1). Prediction ofabsorption, distribution, and toxicity parameters was employed using preADMET and Toxtree. Interactions betweentamoxifen and ERα were determined and the differences in the binding modes between tamoxifen and chalcones wereobserved. Modifina3 had pharmacophore fit score value of 76.42% and the molecular docking studies showed thelowest free energy binding (∆G) of −11.07 kcal/mol while tamoxifen of −10.15 kcal/mol. Modifina3 had absorptionand distribution properties with the percentage human intestinal absorption of 95.90%, CaCO2 of 46.95%, and proteinplasma binding of 93.55%. Toxicity prediction of Modifina3 was categorized in class III and risk assessment requirescompound specific toxicity data. These results suggest that Modifina3 has the potency to be a novel therapeuticcompound for potent ERα inhibitor targeted breast cancer.