In silico predictive for modification of chalcone with pyrazole derivatives as a novel therapeutic compound for targeted breast cancer treatment

  • Jurnal Internasional Bereputasi
  • Riska Prasetiawati, Adel Zamri, Melisa Intan Barliana, Muchtaridi Muchtaridi
  • Journal of Applied Pharmaceutical Science Vol. 9(02), pp 020-028, February, 2019 Available online at DOI: 10.7324/JAPS.2019.90203 ISSN 2231-3354


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

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