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ADMET and DMPK, Vol. 7 No. 3, 2019.

Original scientific paper

https://doi.org/10.5599/admet.678

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

Daniela A. Ramirez ; Instituto de Biología Agrícola de Mendoza (IBAM), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET). Almirante Brown 500, Chacras de Coria, Mendoza, Argentina
Eduardo J. Marchevsky ; Área de Química Analítica, Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, Chacabuco y Pedernera 5700 San Luis, Argentina
Juan M. Luco ; Área de Química Analítica, Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, Chacabuco y Pedernera 5700 San Luis, Argentina
Alejandra B. Camargo ; Instituto de Biología Agrícola de Mendoza (IBAM), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET). Almirante Brown 500, Chacras de Coria, Mendoza, Argentina

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Abstract

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.

Keywords

Quantitative structure-activity relationship (QSAR); CYP2A6; Inhibitors; Organosulfur compounds

Hrčak ID:

224003

URI

https://hrcak.srce.hr/224003

Publication date:

5.8.2019.

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