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In-silico Investigations of quinine and quinidine as potential Inhibitors of AKR1B1 and AKR1B10: Functional and structural characterization
The aberrant expression of aldo keto reductases (AKR1B1 & AKR1B10) has been extensively studied in different types of cancer especially the colon cancer but a very few studies have yet been reported regarding the discovery of inhibitors for the treatment of colon cancer by targeting these isozym...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9612481/ https://www.ncbi.nlm.nih.gov/pubmed/36301939 http://dx.doi.org/10.1371/journal.pone.0271602 |
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author | Ejaz, Syeda Abida Saeed, Amna Birmani, Pervez Rashid Katubi, Khadijah Mohammedsalaeh Elqahtani, Zainab Mufarreh Al-Buriahi, M. S. Ujan, Rabail Siddique, Farhan Ahmed, Samia ben Alrowaili, Z. A. |
author_facet | Ejaz, Syeda Abida Saeed, Amna Birmani, Pervez Rashid Katubi, Khadijah Mohammedsalaeh Elqahtani, Zainab Mufarreh Al-Buriahi, M. S. Ujan, Rabail Siddique, Farhan Ahmed, Samia ben Alrowaili, Z. A. |
author_sort | Ejaz, Syeda Abida |
collection | PubMed |
description | The aberrant expression of aldo keto reductases (AKR1B1 & AKR1B10) has been extensively studied in different types of cancer especially the colon cancer but a very few studies have yet been reported regarding the discovery of inhibitors for the treatment of colon cancer by targeting these isozymes. Therefore, there is a need of selective inhibitors of both targets for the eradication of colon cancer. Currently, the study is focused on the exploration of two quinolone compounds i.e., (S)-(6-Methoxyquinolin-4-yl)[(1S,2R,4S,5R)-5-vinylquinuclidin-2-yl]methanol (Quinidine) and (R)-(6-Methoxyquinolin-4-yl)[(1S,2S,4S,5R)-5-vinylquinuclidin-2-yl]methanol (Quinine) as the potential inhibitors of AKR1B1 and AKR1B10 via detailed in-silico approach. The structural properties including vibrational frequencies, dipole moment, polarizability and the optimization energies were estimated using density functional theory (DFT) calculations; where both compounds were found chemically reactive. After that, the optimized structures were used for the molecular docking studies and here quinidine was found more selective towards AKR1B1 and quinine exhibited maximum inhibition of AKR1B10. The results of molecular docking studies were validated by molecular dynamics simulations which provided the deep insight of stability of protein ligand complex. At the end, the ADMET properties were determined to demonstrate the druglikeness properties of both selected compounds. These findings suggested further exploration of both compounds at molecular level using different in-vivo and in-vitro approaches that will lead to the designing of potential inhibitor of AKR1B1/AKR1B10 for curing colon cancer and related malignancies. |
format | Online Article Text |
id | pubmed-9612481 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-96124812022-10-28 In-silico Investigations of quinine and quinidine as potential Inhibitors of AKR1B1 and AKR1B10: Functional and structural characterization Ejaz, Syeda Abida Saeed, Amna Birmani, Pervez Rashid Katubi, Khadijah Mohammedsalaeh Elqahtani, Zainab Mufarreh Al-Buriahi, M. S. Ujan, Rabail Siddique, Farhan Ahmed, Samia ben Alrowaili, Z. A. PLoS One Research Article The aberrant expression of aldo keto reductases (AKR1B1 & AKR1B10) has been extensively studied in different types of cancer especially the colon cancer but a very few studies have yet been reported regarding the discovery of inhibitors for the treatment of colon cancer by targeting these isozymes. Therefore, there is a need of selective inhibitors of both targets for the eradication of colon cancer. Currently, the study is focused on the exploration of two quinolone compounds i.e., (S)-(6-Methoxyquinolin-4-yl)[(1S,2R,4S,5R)-5-vinylquinuclidin-2-yl]methanol (Quinidine) and (R)-(6-Methoxyquinolin-4-yl)[(1S,2S,4S,5R)-5-vinylquinuclidin-2-yl]methanol (Quinine) as the potential inhibitors of AKR1B1 and AKR1B10 via detailed in-silico approach. The structural properties including vibrational frequencies, dipole moment, polarizability and the optimization energies were estimated using density functional theory (DFT) calculations; where both compounds were found chemically reactive. After that, the optimized structures were used for the molecular docking studies and here quinidine was found more selective towards AKR1B1 and quinine exhibited maximum inhibition of AKR1B10. The results of molecular docking studies were validated by molecular dynamics simulations which provided the deep insight of stability of protein ligand complex. At the end, the ADMET properties were determined to demonstrate the druglikeness properties of both selected compounds. These findings suggested further exploration of both compounds at molecular level using different in-vivo and in-vitro approaches that will lead to the designing of potential inhibitor of AKR1B1/AKR1B10 for curing colon cancer and related malignancies. Public Library of Science 2022-10-27 /pmc/articles/PMC9612481/ /pubmed/36301939 http://dx.doi.org/10.1371/journal.pone.0271602 Text en © 2022 Ejaz 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 Ejaz, Syeda Abida Saeed, Amna Birmani, Pervez Rashid Katubi, Khadijah Mohammedsalaeh Elqahtani, Zainab Mufarreh Al-Buriahi, M. S. Ujan, Rabail Siddique, Farhan Ahmed, Samia ben Alrowaili, Z. A. In-silico Investigations of quinine and quinidine as potential Inhibitors of AKR1B1 and AKR1B10: Functional and structural characterization |
title | In-silico Investigations of quinine and quinidine as potential Inhibitors of AKR1B1 and AKR1B10: Functional and structural characterization |
title_full | In-silico Investigations of quinine and quinidine as potential Inhibitors of AKR1B1 and AKR1B10: Functional and structural characterization |
title_fullStr | In-silico Investigations of quinine and quinidine as potential Inhibitors of AKR1B1 and AKR1B10: Functional and structural characterization |
title_full_unstemmed | In-silico Investigations of quinine and quinidine as potential Inhibitors of AKR1B1 and AKR1B10: Functional and structural characterization |
title_short | In-silico Investigations of quinine and quinidine as potential Inhibitors of AKR1B1 and AKR1B10: Functional and structural characterization |
title_sort | in-silico investigations of quinine and quinidine as potential inhibitors of akr1b1 and akr1b10: functional and structural characterization |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9612481/ https://www.ncbi.nlm.nih.gov/pubmed/36301939 http://dx.doi.org/10.1371/journal.pone.0271602 |
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