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Phytoconstituents of Withania somnifera unveiled Ashwagandhanolide as a potential drug targeting breast cancer: Investigations through computational, molecular docking and conceptual DFT studies
Breast cancer is the second most common malignancy in females worldwide and poses a great challenge that necessitates the identification of novel therapeutic agents from several sources. This research aimed to study the molecular docking and molecular dynamics simulations of four proteins (such as P...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Public Library of Science
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9536605/ https://www.ncbi.nlm.nih.gov/pubmed/36201520 http://dx.doi.org/10.1371/journal.pone.0275432 |
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author | Gowtham, Hittanahallikoppal Gajendramurthy Murali, Mahadevamurthy Singh, Sudarshana Brijesh Shivamallu, Chandan Pradeep, Sushma Shivakumar, C. S. Anandan, Satish Thampy, Anjana Achar, Raghu Ram Silina, Ekaterina Stupin, Victor Ortega-Castro, Joaquín Frau, Juan Flores-Holguín, Norma Amruthesh, Kestur Nagaraj Kollur, Shiva Prasad Glossman-Mitnik, Daniel |
author_facet | Gowtham, Hittanahallikoppal Gajendramurthy Murali, Mahadevamurthy Singh, Sudarshana Brijesh Shivamallu, Chandan Pradeep, Sushma Shivakumar, C. S. Anandan, Satish Thampy, Anjana Achar, Raghu Ram Silina, Ekaterina Stupin, Victor Ortega-Castro, Joaquín Frau, Juan Flores-Holguín, Norma Amruthesh, Kestur Nagaraj Kollur, Shiva Prasad Glossman-Mitnik, Daniel |
author_sort | Gowtham, Hittanahallikoppal Gajendramurthy |
collection | PubMed |
description | Breast cancer is the second most common malignancy in females worldwide and poses a great challenge that necessitates the identification of novel therapeutic agents from several sources. This research aimed to study the molecular docking and molecular dynamics simulations of four proteins (such as PDB: 6CBZ, 1FDW, 5GWK and 2WTT) with the selected phytochemicals from Withania somnifera to identify the potential inhibitors for breast cancer. The molecular docking result showed that among 44 compounds, two of them, Ashwagandhanolide and Withanolide sulfoxide have the potential to inhibit estrogen receptor alpha (ERα), 17-beta-hydroxysteroid -dehydrogenase type 1 (17β-HSD1), topoisomerase II alpha (TOP2A) and p73 tetramerization domain that are expressed during breast cancer. The molecular dynamics (MD) simulations results suggested that Ashwagandhanolide remained inside the binding cavity of four targeted proteins and contributed favorably towards forming a stable protein-ligand complex throughout the simulation. Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) properties confirmed that Ashwagandhanolide is hydrophobic and has moderate intestinal permeability, good intestinal absorption, and poor skin permeability. The compound has a relatively low VDss value (-1.652) and can be transported across ABC transporter and good central nervous system (CNS) permeability but did not easily cross the blood-brain barrier (BBB). This compound does not possess any mutagenicity, hepatotoxicity and skin sensitization. Based on the results obtained, the present study highlights the anticancer potential of Ashwagandhanolide, a compound from W. somnifera. Furthermore, in vitro and in vivo studies are necessary to perform before clinical trials to prove the potentiality of Ashwagandhanolide. |
format | Online Article Text |
id | pubmed-9536605 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-95366052022-10-07 Phytoconstituents of Withania somnifera unveiled Ashwagandhanolide as a potential drug targeting breast cancer: Investigations through computational, molecular docking and conceptual DFT studies Gowtham, Hittanahallikoppal Gajendramurthy Murali, Mahadevamurthy Singh, Sudarshana Brijesh Shivamallu, Chandan Pradeep, Sushma Shivakumar, C. S. Anandan, Satish Thampy, Anjana Achar, Raghu Ram Silina, Ekaterina Stupin, Victor Ortega-Castro, Joaquín Frau, Juan Flores-Holguín, Norma Amruthesh, Kestur Nagaraj Kollur, Shiva Prasad Glossman-Mitnik, Daniel PLoS One Research Article Breast cancer is the second most common malignancy in females worldwide and poses a great challenge that necessitates the identification of novel therapeutic agents from several sources. This research aimed to study the molecular docking and molecular dynamics simulations of four proteins (such as PDB: 6CBZ, 1FDW, 5GWK and 2WTT) with the selected phytochemicals from Withania somnifera to identify the potential inhibitors for breast cancer. The molecular docking result showed that among 44 compounds, two of them, Ashwagandhanolide and Withanolide sulfoxide have the potential to inhibit estrogen receptor alpha (ERα), 17-beta-hydroxysteroid -dehydrogenase type 1 (17β-HSD1), topoisomerase II alpha (TOP2A) and p73 tetramerization domain that are expressed during breast cancer. The molecular dynamics (MD) simulations results suggested that Ashwagandhanolide remained inside the binding cavity of four targeted proteins and contributed favorably towards forming a stable protein-ligand complex throughout the simulation. Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) properties confirmed that Ashwagandhanolide is hydrophobic and has moderate intestinal permeability, good intestinal absorption, and poor skin permeability. The compound has a relatively low VDss value (-1.652) and can be transported across ABC transporter and good central nervous system (CNS) permeability but did not easily cross the blood-brain barrier (BBB). This compound does not possess any mutagenicity, hepatotoxicity and skin sensitization. Based on the results obtained, the present study highlights the anticancer potential of Ashwagandhanolide, a compound from W. somnifera. Furthermore, in vitro and in vivo studies are necessary to perform before clinical trials to prove the potentiality of Ashwagandhanolide. Public Library of Science 2022-10-06 /pmc/articles/PMC9536605/ /pubmed/36201520 http://dx.doi.org/10.1371/journal.pone.0275432 Text en © 2022 Gowtham et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Gowtham, Hittanahallikoppal Gajendramurthy Murali, Mahadevamurthy Singh, Sudarshana Brijesh Shivamallu, Chandan Pradeep, Sushma Shivakumar, C. S. Anandan, Satish Thampy, Anjana Achar, Raghu Ram Silina, Ekaterina Stupin, Victor Ortega-Castro, Joaquín Frau, Juan Flores-Holguín, Norma Amruthesh, Kestur Nagaraj Kollur, Shiva Prasad Glossman-Mitnik, Daniel Phytoconstituents of Withania somnifera unveiled Ashwagandhanolide as a potential drug targeting breast cancer: Investigations through computational, molecular docking and conceptual DFT studies |
title | Phytoconstituents of Withania somnifera unveiled Ashwagandhanolide as a potential drug targeting breast cancer: Investigations through computational, molecular docking and conceptual DFT studies |
title_full | Phytoconstituents of Withania somnifera unveiled Ashwagandhanolide as a potential drug targeting breast cancer: Investigations through computational, molecular docking and conceptual DFT studies |
title_fullStr | Phytoconstituents of Withania somnifera unveiled Ashwagandhanolide as a potential drug targeting breast cancer: Investigations through computational, molecular docking and conceptual DFT studies |
title_full_unstemmed | Phytoconstituents of Withania somnifera unveiled Ashwagandhanolide as a potential drug targeting breast cancer: Investigations through computational, molecular docking and conceptual DFT studies |
title_short | Phytoconstituents of Withania somnifera unveiled Ashwagandhanolide as a potential drug targeting breast cancer: Investigations through computational, molecular docking and conceptual DFT studies |
title_sort | phytoconstituents of withania somnifera unveiled ashwagandhanolide as a potential drug targeting breast cancer: investigations through computational, molecular docking and conceptual dft studies |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9536605/ https://www.ncbi.nlm.nih.gov/pubmed/36201520 http://dx.doi.org/10.1371/journal.pone.0275432 |
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