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Toluene Dioxygenase-Catalyzed cis-Dihydroxylation of Quinolines: A Molecular Docking Study and Chemoenzymatic Synthesis of Quinoline Arene Oxides
Molecular docking studies of quinoline and 2-chloroquinoline substrates at the active site of toluene dioxygenase (TDO), were conducted using Autodock Vina, to identify novel edge-to-face interactions and to rationalize the observed stereoselective cis-dihydroxylation of carbocyclic rings and format...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907597/ https://www.ncbi.nlm.nih.gov/pubmed/33644006 http://dx.doi.org/10.3389/fbioe.2020.619175 |
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author | Boyd, Derek R. Sharma, Narain D. Loke, Pui L. Carroll, Jonathan G. Stevenson, Paul J. Hoering, Patrick Allen, Christopher C. R. |
author_facet | Boyd, Derek R. Sharma, Narain D. Loke, Pui L. Carroll, Jonathan G. Stevenson, Paul J. Hoering, Patrick Allen, Christopher C. R. |
author_sort | Boyd, Derek R. |
collection | PubMed |
description | Molecular docking studies of quinoline and 2-chloroquinoline substrates at the active site of toluene dioxygenase (TDO), were conducted using Autodock Vina, to identify novel edge-to-face interactions and to rationalize the observed stereoselective cis-dihydroxylation of carbocyclic rings and formation of isolable cis-dihydrodiol metabolites. These in silico docking results of quinoline and pyridine substrates, with TDO, also provided support for the postulated cis-dihydroxylation of electron-deficient pyridyl rings, to give transient cis-dihydrodiol intermediates and the derived hydroxyquinolines. 2-Chloroquinoline cis-dihydrodiol metabolites were used as precursors in the chemoenzymatic synthesis of enantiopure arene oxide and arene dioxide derivatives of quinoline, in the context of its possible mammalian metabolism and carcinogenicity. |
format | Online Article Text |
id | pubmed-7907597 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-79075972021-02-27 Toluene Dioxygenase-Catalyzed cis-Dihydroxylation of Quinolines: A Molecular Docking Study and Chemoenzymatic Synthesis of Quinoline Arene Oxides Boyd, Derek R. Sharma, Narain D. Loke, Pui L. Carroll, Jonathan G. Stevenson, Paul J. Hoering, Patrick Allen, Christopher C. R. Front Bioeng Biotechnol Bioengineering and Biotechnology Molecular docking studies of quinoline and 2-chloroquinoline substrates at the active site of toluene dioxygenase (TDO), were conducted using Autodock Vina, to identify novel edge-to-face interactions and to rationalize the observed stereoselective cis-dihydroxylation of carbocyclic rings and formation of isolable cis-dihydrodiol metabolites. These in silico docking results of quinoline and pyridine substrates, with TDO, also provided support for the postulated cis-dihydroxylation of electron-deficient pyridyl rings, to give transient cis-dihydrodiol intermediates and the derived hydroxyquinolines. 2-Chloroquinoline cis-dihydrodiol metabolites were used as precursors in the chemoenzymatic synthesis of enantiopure arene oxide and arene dioxide derivatives of quinoline, in the context of its possible mammalian metabolism and carcinogenicity. Frontiers Media S.A. 2021-02-12 /pmc/articles/PMC7907597/ /pubmed/33644006 http://dx.doi.org/10.3389/fbioe.2020.619175 Text en Copyright © 2021 Boyd, Sharma, Loke, Carroll, Stevenson, Hoering and Allen. http://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 | Bioengineering and Biotechnology Boyd, Derek R. Sharma, Narain D. Loke, Pui L. Carroll, Jonathan G. Stevenson, Paul J. Hoering, Patrick Allen, Christopher C. R. Toluene Dioxygenase-Catalyzed cis-Dihydroxylation of Quinolines: A Molecular Docking Study and Chemoenzymatic Synthesis of Quinoline Arene Oxides |
title | Toluene Dioxygenase-Catalyzed cis-Dihydroxylation of Quinolines: A Molecular Docking Study and Chemoenzymatic Synthesis of Quinoline Arene Oxides |
title_full | Toluene Dioxygenase-Catalyzed cis-Dihydroxylation of Quinolines: A Molecular Docking Study and Chemoenzymatic Synthesis of Quinoline Arene Oxides |
title_fullStr | Toluene Dioxygenase-Catalyzed cis-Dihydroxylation of Quinolines: A Molecular Docking Study and Chemoenzymatic Synthesis of Quinoline Arene Oxides |
title_full_unstemmed | Toluene Dioxygenase-Catalyzed cis-Dihydroxylation of Quinolines: A Molecular Docking Study and Chemoenzymatic Synthesis of Quinoline Arene Oxides |
title_short | Toluene Dioxygenase-Catalyzed cis-Dihydroxylation of Quinolines: A Molecular Docking Study and Chemoenzymatic Synthesis of Quinoline Arene Oxides |
title_sort | toluene dioxygenase-catalyzed cis-dihydroxylation of quinolines: a molecular docking study and chemoenzymatic synthesis of quinoline arene oxides |
topic | Bioengineering and Biotechnology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907597/ https://www.ncbi.nlm.nih.gov/pubmed/33644006 http://dx.doi.org/10.3389/fbioe.2020.619175 |
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