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Artonin E and Structural Analogs from Artocarpus Species Abrogates Estrogen Receptor Signaling in Breast Cancer
The increasing rate of mortality ensued from breast cancer has encouraged research into safer and efficient therapy. The human Estrogen receptor α has been implicated in the majority of reported breast cancer cases. Molecular docking employing Glide, Schrodinger suite 2015, was used to study the bin...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6272880/ https://www.ncbi.nlm.nih.gov/pubmed/27367662 http://dx.doi.org/10.3390/molecules21070839 |
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author | Etti, Imaobong Abdullah, Rasedee Hashim, Najihah Mohd Kadir, Arifah Abdul, Ahmad Bustamam Etti, Christopher Malami, Ibrahim Waziri, Peter How, Chee Wun |
author_facet | Etti, Imaobong Abdullah, Rasedee Hashim, Najihah Mohd Kadir, Arifah Abdul, Ahmad Bustamam Etti, Christopher Malami, Ibrahim Waziri, Peter How, Chee Wun |
author_sort | Etti, Imaobong |
collection | PubMed |
description | The increasing rate of mortality ensued from breast cancer has encouraged research into safer and efficient therapy. The human Estrogen receptor α has been implicated in the majority of reported breast cancer cases. Molecular docking employing Glide, Schrodinger suite 2015, was used to study the binding affinities of small molecules from the Artocarpus species after their drug-like properties were ascertained. The structure of the ligand-binding domain of human Estrogen receptor α was retrieved from Protein Data Bank while the structures of compounds were collected from PubChem database. The binding interactions of the studied compounds were reported as well as their glide scores. The best glide scored ligand, was Artonin E with a score of −12.72 Kcal when compared to other studied phytomolecules and it evoked growth inhibition of an estrogen receptor positive breast cancer cells in submicromolar concentration (3.8–6.9 µM) in comparison to a reference standard Tamoxifen (18.9–24.1 µM) within the tested time point (24–72 h). The studied ligands, which had good interactions with the target receptor, were also drug-like when compared with 95% of orally available drugs with the exception of Artoelastin, whose predicted physicochemical properties rendered it less drug-like. The in silico physicochemical properties, docking interactions and growth inhibition of the best glide scorer are indications of the anti-breast cancer relevance of the studied molecules. |
format | Online Article Text |
id | pubmed-6272880 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-62728802018-12-28 Artonin E and Structural Analogs from Artocarpus Species Abrogates Estrogen Receptor Signaling in Breast Cancer Etti, Imaobong Abdullah, Rasedee Hashim, Najihah Mohd Kadir, Arifah Abdul, Ahmad Bustamam Etti, Christopher Malami, Ibrahim Waziri, Peter How, Chee Wun Molecules Article The increasing rate of mortality ensued from breast cancer has encouraged research into safer and efficient therapy. The human Estrogen receptor α has been implicated in the majority of reported breast cancer cases. Molecular docking employing Glide, Schrodinger suite 2015, was used to study the binding affinities of small molecules from the Artocarpus species after their drug-like properties were ascertained. The structure of the ligand-binding domain of human Estrogen receptor α was retrieved from Protein Data Bank while the structures of compounds were collected from PubChem database. The binding interactions of the studied compounds were reported as well as their glide scores. The best glide scored ligand, was Artonin E with a score of −12.72 Kcal when compared to other studied phytomolecules and it evoked growth inhibition of an estrogen receptor positive breast cancer cells in submicromolar concentration (3.8–6.9 µM) in comparison to a reference standard Tamoxifen (18.9–24.1 µM) within the tested time point (24–72 h). The studied ligands, which had good interactions with the target receptor, were also drug-like when compared with 95% of orally available drugs with the exception of Artoelastin, whose predicted physicochemical properties rendered it less drug-like. The in silico physicochemical properties, docking interactions and growth inhibition of the best glide scorer are indications of the anti-breast cancer relevance of the studied molecules. MDPI 2016-06-29 /pmc/articles/PMC6272880/ /pubmed/27367662 http://dx.doi.org/10.3390/molecules21070839 Text en © 2016 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Etti, Imaobong Abdullah, Rasedee Hashim, Najihah Mohd Kadir, Arifah Abdul, Ahmad Bustamam Etti, Christopher Malami, Ibrahim Waziri, Peter How, Chee Wun Artonin E and Structural Analogs from Artocarpus Species Abrogates Estrogen Receptor Signaling in Breast Cancer |
title | Artonin E and Structural Analogs from Artocarpus Species Abrogates Estrogen Receptor Signaling in Breast Cancer |
title_full | Artonin E and Structural Analogs from Artocarpus Species Abrogates Estrogen Receptor Signaling in Breast Cancer |
title_fullStr | Artonin E and Structural Analogs from Artocarpus Species Abrogates Estrogen Receptor Signaling in Breast Cancer |
title_full_unstemmed | Artonin E and Structural Analogs from Artocarpus Species Abrogates Estrogen Receptor Signaling in Breast Cancer |
title_short | Artonin E and Structural Analogs from Artocarpus Species Abrogates Estrogen Receptor Signaling in Breast Cancer |
title_sort | artonin e and structural analogs from artocarpus species abrogates estrogen receptor signaling in breast cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6272880/ https://www.ncbi.nlm.nih.gov/pubmed/27367662 http://dx.doi.org/10.3390/molecules21070839 |
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