Molecular Docking and 3D-Pharmacophore Modeling to Study the Interactions of Chalcone Derivatives with Estrogen Receptor Alpha
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-dimethylcha...
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MDPI AG
2017-10-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/10/4/81 |
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| author | Muchtaridi Muchtaridi Hasna Nur Syahidah Anas Subarnas Muhammad Yusuf Sharon D. Bryant Thierry Langer |
| author_facet | Muchtaridi Muchtaridi Hasna Nur Syahidah Anas Subarnas Muhammad Yusuf Sharon D. Bryant Thierry Langer |
| author_sort | Muchtaridi Muchtaridi |
| collection | DOAJ |
| description | 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. |
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| issn | 1424-8247 |
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| last_indexed | 2024-12-13T08:36:01Z |
| publishDate | 2017-10-01 |
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| series | Pharmaceuticals |
| spelling | doaj.art-4725efac03e24fb0879dd8321c2c06942022-12-21T23:53:38ZengMDPI AGPharmaceuticals1424-82472017-10-011048110.3390/ph10040081ph10040081Molecular Docking and 3D-Pharmacophore Modeling to Study the Interactions of Chalcone Derivatives with Estrogen Receptor AlphaMuchtaridi Muchtaridi0Hasna Nur Syahidah1Anas Subarnas2Muhammad Yusuf3Sharon D. Bryant4Thierry Langer5Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, Jln. Raya Bandung Sumedang KM. 21, Jatinangor 45363, West Java, IndonesiaDepartment of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, Jln. Raya Bandung Sumedang KM. 21, Jatinangor 45363, West Java, IndonesiaDepartment of Pharmacology, Faculty of Pharmacy, Universitas Padjadjaran, Jln. Raya Bandung-Sumedang KM. 21, Jatinangor 45363, West Java, IndonesiaDepartment of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jln. Raya Bandung-Sumedang KM. 21, Jatinangor 45363, West Java, IndonesiaInte: Ligand GmbH, Mariahilferstrasse 74B/11, A-1070 Vienna, AustriaDepartment of Pharmaceutical Chemistry, Faculty of Life Sciences, University of Vienna, Althanstraße 14, A-1090 Vienna, AustriaTamoxifen 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.https://www.mdpi.com/1424-8247/10/4/81chalconemolecular dockingstructure-based 3D pharmacophore modelinganti-breast cancerestrogen receptor αMCF-7 |
| spellingShingle | Muchtaridi Muchtaridi Hasna Nur Syahidah Anas Subarnas Muhammad Yusuf Sharon D. Bryant Thierry Langer Molecular Docking and 3D-Pharmacophore Modeling to Study the Interactions of Chalcone Derivatives with Estrogen Receptor Alpha Pharmaceuticals chalcone molecular docking structure-based 3D pharmacophore modeling anti-breast cancer estrogen receptor α MCF-7 |
| title | Molecular Docking and 3D-Pharmacophore Modeling to Study the Interactions of Chalcone Derivatives with Estrogen Receptor Alpha |
| title_full | Molecular Docking and 3D-Pharmacophore Modeling to Study the Interactions of Chalcone Derivatives with Estrogen Receptor Alpha |
| title_fullStr | Molecular Docking and 3D-Pharmacophore Modeling to Study the Interactions of Chalcone Derivatives with Estrogen Receptor Alpha |
| title_full_unstemmed | Molecular Docking and 3D-Pharmacophore Modeling to Study the Interactions of Chalcone Derivatives with Estrogen Receptor Alpha |
| title_short | Molecular Docking and 3D-Pharmacophore Modeling to Study the Interactions of Chalcone Derivatives with Estrogen Receptor Alpha |
| title_sort | molecular docking and 3d pharmacophore modeling to study the interactions of chalcone derivatives with estrogen receptor alpha |
| topic | chalcone molecular docking structure-based 3D pharmacophore modeling anti-breast cancer estrogen receptor α MCF-7 |
| url | https://www.mdpi.com/1424-8247/10/4/81 |
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