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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Detalles Bibliográficos
Autores: Ramirez, Daniela Andrea, Marchevsky, Eduardo Jorge, Luco, Juan Maria, Camargo, Alejandra Beatriz
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/104663
Acceso en línea:http://hdl.handle.net/11336/104663
Access Level:acceso abierto
Palabra clave:QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP (QSAR)
CYP2A6
INHIBITORS
ORGANOSULFUR COMPOUNDS
https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
Descripción
Sumario: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.