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Quantitative structure-activity relationship to elucidate human CYP2A6 inhibition by organosulfur compounds

CYP2A6 is a human enzyme responsible for the metabolic elimination of nicotine, and it is also involved in the activation of procarcinogenic nitrosamines, especially those present in tobacco smoke. Several investigations have reported that reducing this enzyme activity may contribute to anti-smoking...

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Autores principales: Ramirez, Daniela A., Marchevsky, Eduardo J., Luco, Juan M., Camargo, Alejandra B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: International Association of Physical Chemists 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8957234/
https://www.ncbi.nlm.nih.gov/pubmed/35350661
http://dx.doi.org/10.5599/admet.678
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author Ramirez, Daniela A.
Marchevsky, Eduardo J.
Luco, Juan M.
Camargo, Alejandra B.
author_facet Ramirez, Daniela A.
Marchevsky, Eduardo J.
Luco, Juan M.
Camargo, Alejandra B.
author_sort Ramirez, Daniela A.
collection PubMed
description CYP2A6 is a human enzyme responsible for the metabolic elimination of nicotine, and it is also involved in the activation of procarcinogenic nitrosamines, especially those present in tobacco smoke. Several investigations have reported that reducing this enzyme activity may contribute to anti-smoking therapy as well as reducing the risk of promutagens in the body. For these reasons, several authors investigate selective inhibitors molecules toward this enzyme. The aim of this study was to evaluate the interactions between a set of organosulfur compounds and the CYP2A6 enzyme by a quantitative structure-activity relationship (QSAR) analysis. The present work provides a better understanding of the mechanisms involved, with the final goal of providing information for the future design of CYP2A6 inhibitors based on dietary compounds. The reported activity data were modeled by means of multiple regression analysis (MLR) and partial least-squares (PLS) techniques. The results indicate that hydrophobic and steric factors govern the union, while electronic factors are strongly involved in the case of monosulfides.
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spelling pubmed-89572342022-03-28 Quantitative structure-activity relationship to elucidate human CYP2A6 inhibition by organosulfur compounds Ramirez, Daniela A. Marchevsky, Eduardo J. Luco, Juan M. Camargo, Alejandra B. ADMET DMPK Original Scientific Paper CYP2A6 is a human enzyme responsible for the metabolic elimination of nicotine, and it is also involved in the activation of procarcinogenic nitrosamines, especially those present in tobacco smoke. Several investigations have reported that reducing this enzyme activity may contribute to anti-smoking therapy as well as reducing the risk of promutagens in the body. For these reasons, several authors investigate selective inhibitors molecules toward this enzyme. The aim of this study was to evaluate the interactions between a set of organosulfur compounds and the CYP2A6 enzyme by a quantitative structure-activity relationship (QSAR) analysis. The present work provides a better understanding of the mechanisms involved, with the final goal of providing information for the future design of CYP2A6 inhibitors based on dietary compounds. The reported activity data were modeled by means of multiple regression analysis (MLR) and partial least-squares (PLS) techniques. The results indicate that hydrophobic and steric factors govern the union, while electronic factors are strongly involved in the case of monosulfides. International Association of Physical Chemists 2019-08-05 /pmc/articles/PMC8957234/ /pubmed/35350661 http://dx.doi.org/10.5599/admet.678 Text en Copyright © 2019 by the authors. https://creativecommons.org/licenses/by/3.0/This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/ (https://creativecommons.org/licenses/by/3.0/) ).
spellingShingle Original Scientific Paper
Ramirez, Daniela A.
Marchevsky, Eduardo J.
Luco, Juan M.
Camargo, Alejandra B.
Quantitative structure-activity relationship to elucidate human CYP2A6 inhibition by organosulfur compounds
title Quantitative structure-activity relationship to elucidate human CYP2A6 inhibition by organosulfur compounds
title_full Quantitative structure-activity relationship to elucidate human CYP2A6 inhibition by organosulfur compounds
title_fullStr Quantitative structure-activity relationship to elucidate human CYP2A6 inhibition by organosulfur compounds
title_full_unstemmed Quantitative structure-activity relationship to elucidate human CYP2A6 inhibition by organosulfur compounds
title_short Quantitative structure-activity relationship to elucidate human CYP2A6 inhibition by organosulfur compounds
title_sort quantitative structure-activity relationship to elucidate human cyp2a6 inhibition by organosulfur compounds
topic Original Scientific Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8957234/
https://www.ncbi.nlm.nih.gov/pubmed/35350661
http://dx.doi.org/10.5599/admet.678
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