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Amomum subulatum: A treasure trove of anti-cancer compounds targeting TP53 protein using in vitro and in silico techniques
Cancer is a primary global health concern, and researchers seek innovative approaches to combat the disease. Clinical bioinformatics and high-throughput proteomics technologies provide powerful tools to explore cancer biology. Medicinal plants are considered effective therapeutic agents, and compute...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10189520/ https://www.ncbi.nlm.nih.gov/pubmed/37206196 http://dx.doi.org/10.3389/fchem.2023.1174363 |
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author | Ali, Sadaqat Noreen, Asifa Qamar, Adeem Zafar, Imran Ain, Quratul Nafidi, Hiba-Allah Bin Jardan, Yousef A. Bourhia, Mohammed Rashid, Summya Sharma, Rohit |
author_facet | Ali, Sadaqat Noreen, Asifa Qamar, Adeem Zafar, Imran Ain, Quratul Nafidi, Hiba-Allah Bin Jardan, Yousef A. Bourhia, Mohammed Rashid, Summya Sharma, Rohit |
author_sort | Ali, Sadaqat |
collection | PubMed |
description | Cancer is a primary global health concern, and researchers seek innovative approaches to combat the disease. Clinical bioinformatics and high-throughput proteomics technologies provide powerful tools to explore cancer biology. Medicinal plants are considered effective therapeutic agents, and computer-aided drug design (CAAD) is used to identify novel drug candidates from plant extracts. The tumour suppressor protein TP53 is an attractive target for drug development, given its crucial role in cancer pathogenesis. This study used a dried extract of Amomum subulatum seeds to identify phytocompounds targeting TP53 in cancer. We apply qualitative tests to determine its phytochemicals (Alkaloid, Tannin, Saponin, Phlobatinin, and Cardic glycoside), and found that alkaloid composed of 9.4% ± 0.04% and Saponin 1.9% ± 0.05% crude chemical constituent. In the results of DPPH Analysis Amomum subulatum Seeds founded antioxidant activity, and then we verified via observing methanol extract (79.82%), BHT (81.73%), and n-hexane extract (51.31%) found to be positive. For Inhibition of oxidation, we observe BHT is 90.25%, and Methanol (83.42%) has the most significant proportion of linoleic acid oxidation suppression. We used diverse bioinformatics approaches to evaluate the effect of A. subulatum seeds and their natural components on TP53. Compound-1 had the best pharmacophore match value (53.92), with others ranging from 50.75 to 53.92. Our docking result shows the top three natural compounds had the highest binding energies (−11.10 to −10.3 kcal/mol). The highest binding energies (−10.9 to −9.2 kcal/mol) compound bonded to significant sections in the target protein’s active domains with TP53. Based on virtual screening, we select top phytocompounds for targets which highly fit based on pharmacophore score and observe these compounds exhibited potent antioxidant activity and inhibited cancer cell inflammation in the TP53 pathway. Molecular Dynamics (MD) simulations indicated that the ligand was bound to the protein with some significant conformational changes in the protein structure. This study provides novel insights into the development of innovative drugs for the treatment of cancer disorders. |
format | Online Article Text |
id | pubmed-10189520 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-101895202023-05-18 Amomum subulatum: A treasure trove of anti-cancer compounds targeting TP53 protein using in vitro and in silico techniques Ali, Sadaqat Noreen, Asifa Qamar, Adeem Zafar, Imran Ain, Quratul Nafidi, Hiba-Allah Bin Jardan, Yousef A. Bourhia, Mohammed Rashid, Summya Sharma, Rohit Front Chem Chemistry Cancer is a primary global health concern, and researchers seek innovative approaches to combat the disease. Clinical bioinformatics and high-throughput proteomics technologies provide powerful tools to explore cancer biology. Medicinal plants are considered effective therapeutic agents, and computer-aided drug design (CAAD) is used to identify novel drug candidates from plant extracts. The tumour suppressor protein TP53 is an attractive target for drug development, given its crucial role in cancer pathogenesis. This study used a dried extract of Amomum subulatum seeds to identify phytocompounds targeting TP53 in cancer. We apply qualitative tests to determine its phytochemicals (Alkaloid, Tannin, Saponin, Phlobatinin, and Cardic glycoside), and found that alkaloid composed of 9.4% ± 0.04% and Saponin 1.9% ± 0.05% crude chemical constituent. In the results of DPPH Analysis Amomum subulatum Seeds founded antioxidant activity, and then we verified via observing methanol extract (79.82%), BHT (81.73%), and n-hexane extract (51.31%) found to be positive. For Inhibition of oxidation, we observe BHT is 90.25%, and Methanol (83.42%) has the most significant proportion of linoleic acid oxidation suppression. We used diverse bioinformatics approaches to evaluate the effect of A. subulatum seeds and their natural components on TP53. Compound-1 had the best pharmacophore match value (53.92), with others ranging from 50.75 to 53.92. Our docking result shows the top three natural compounds had the highest binding energies (−11.10 to −10.3 kcal/mol). The highest binding energies (−10.9 to −9.2 kcal/mol) compound bonded to significant sections in the target protein’s active domains with TP53. Based on virtual screening, we select top phytocompounds for targets which highly fit based on pharmacophore score and observe these compounds exhibited potent antioxidant activity and inhibited cancer cell inflammation in the TP53 pathway. Molecular Dynamics (MD) simulations indicated that the ligand was bound to the protein with some significant conformational changes in the protein structure. This study provides novel insights into the development of innovative drugs for the treatment of cancer disorders. Frontiers Media S.A. 2023-04-26 /pmc/articles/PMC10189520/ /pubmed/37206196 http://dx.doi.org/10.3389/fchem.2023.1174363 Text en Copyright © 2023 Ali, Noreen, Qamar, Zafar, Ain, Nafidi, Bin Jardan, Bourhia, Rashid and Sharma. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Chemistry Ali, Sadaqat Noreen, Asifa Qamar, Adeem Zafar, Imran Ain, Quratul Nafidi, Hiba-Allah Bin Jardan, Yousef A. Bourhia, Mohammed Rashid, Summya Sharma, Rohit Amomum subulatum: A treasure trove of anti-cancer compounds targeting TP53 protein using in vitro and in silico techniques |
title |
Amomum subulatum: A treasure trove of anti-cancer compounds targeting TP53 protein using in vitro and in silico techniques |
title_full |
Amomum subulatum: A treasure trove of anti-cancer compounds targeting TP53 protein using in vitro and in silico techniques |
title_fullStr |
Amomum subulatum: A treasure trove of anti-cancer compounds targeting TP53 protein using in vitro and in silico techniques |
title_full_unstemmed |
Amomum subulatum: A treasure trove of anti-cancer compounds targeting TP53 protein using in vitro and in silico techniques |
title_short |
Amomum subulatum: A treasure trove of anti-cancer compounds targeting TP53 protein using in vitro and in silico techniques |
title_sort | amomum subulatum: a treasure trove of anti-cancer compounds targeting tp53 protein using in vitro and in silico techniques |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10189520/ https://www.ncbi.nlm.nih.gov/pubmed/37206196 http://dx.doi.org/10.3389/fchem.2023.1174363 |
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