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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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
International Association of Physical Chemists
2019
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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. |
format | Online Article Text |
id | pubmed-8957234 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | International Association of Physical Chemists |
record_format | MEDLINE/PubMed |
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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