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Pharmaceuticals 2017, 10(4), 81; doi:10.3390/ph10040081

Molecular Docking and 3D-Pharmacophore Modeling to Study the Interactions of Chalcone Derivatives with Estrogen Receptor Alpha

1
Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, Jln. Raya Bandung Sumedang KM. 21, Jatinangor 45363, West Java, Indonesia
2
Department of Pharmacology, Faculty of Pharmacy, Universitas Padjadjaran, Jln. Raya Bandung-Sumedang KM. 21, Jatinangor 45363, West Java, Indonesia
3
Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jln. Raya Bandung-Sumedang KM. 21, Jatinangor 45363, West Java, Indonesia
4
Inte: Ligand GmbH, Mariahilferstrasse 74B/11, A-1070 Vienna, Austria
5
Department of Pharmaceutical Chemistry, Faculty of Life Sciences, University of Vienna, Althanstraße 14, A-1090 Vienna, Austria
*
Author to whom correspondence should be addressed.
Received: 21 August 2017 / Revised: 9 October 2017 / Accepted: 15 October 2017 / Published: 16 October 2017
(This article belongs to the Special Issue Chemoinformatics and Drug Design)
View Full-Text   |   Download PDF [6845 KB, uploaded 16 October 2017]   |  

Abstract

Tamoxifen is the most frequently used anti-estrogen adjuvant treatment for estrogen receptor-positive breast cancer. However, it is associated with an increased risk of several serious side–effects, such as uterine cancer, stroke, and pulmonary embolism. The 2′,4′-dihydroxy-6-methoxy-3,5-dimethylchalcone (ChalcEA) from plant leaves of Eugenia aquea, has been found to inhibit the proliferation of MCF-7 human breast cancer cells in a dose-dependent manner, with an IC50 of 74.5 μg/mL (250 μM). The aim of this work was to study the molecular interactions of new ChalcEA derivatives formed with the Estrogen Receptor α (ERα) using computer aided drug design approaches. Molecular docking using Autodock 4.2 was employed to explore the modes of binding of ChalcEA derivatives with ERα. The 3D structure-based pharmacophore model was derived using LigandScout 4.1 Advanced to investigate the important chemical interactions of the ERα-tamoxifen complex structure. The binding energy and the tamoxifen-pharmacophore fit score of the best ChalcEA derivative (HNS10) were −12.33 kcal/mol and 67.07 kcal/mol, respectively. The HNS10 interacted with Leu346, Thr347, Leu349, Ala350, Glu353, Leu387, Met388, Leu391, Arg394, Met421, and Leu525. These results suggest that the new ChalcEA derivatives could serve as the lead compound for potent ERα inhibitor in the fight against breast cancer. View Full-Text
Keywords: chalcone; molecular docking; structure-based 3D pharmacophore modeling; anti-breast cancer; estrogen receptor α; MCF-7 chalcone; molecular docking; structure-based 3D pharmacophore modeling; anti-breast cancer; estrogen receptor α; MCF-7
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Muchtaridi, M.; Syahidah, H.N.; Subarnas, A.; Yusuf, M.; Bryant, S.D.; Langer, T. Molecular Docking and 3D-Pharmacophore Modeling to Study the Interactions of Chalcone Derivatives with Estrogen Receptor Alpha. Pharmaceuticals 2017, 10, 81.

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