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Goyal et al. J Cancer Metastasis Treat 2021;7:18 Journal of Cancer
DOI: 10.20517/2394-4722.2020.143
Metastasis and Treatment

Original Article Open Access

Identification of CYP 2A6 inhibitors in an effort to
mitigate the harmful effects of the phytochemical

nicotine

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1
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Navneet Goyal , Jayalakshmi Sridhar , Camilla Do , Melyssa Bratton , Shahensha Shaik , Quan Jiang ,
Maryam Foroozesh 1
1
Department of Chemistry, Xavier University of Louisiana, New Orleans, LA 70125, USA.
2
Cell and Molecular Biology and Bioinformatic Core, College of Pharmacy, Xavier University of Louisiana, New Orleans, LA
70125, USA.
Correspondence to: Prof. Maryam Foroozesh, Department of Chemistry, Xavier University of Louisiana, New Orleans, LA 70125,
USA. E-mail: mforooze@xula.edu
How to cite this article: Goyal N, Sridhar J, Do C, Bratton M, Shaik S, Jiang Q, Foroozesh M. Identification of CYP 2A6 inhibitors
in an effort to mitigate the harmful effects of the phytochemical nicotine. J Cancer Metastasis Treat 2021;7:18.
https://dx.doi.org/10.20517/2394-4722.2020.143
Received: 22 Dec 2020 First Decision: 27 Jan 2021 Revised: 8 Feb 2021 Accepted: 3 Mar 2021 Available online: 14 Apr 2021

Academic Editor: Sanjay Gupta Copy Editor: Yue-Yue Zhang Production Editor: Yue-Yue Zhang

Abstract
Aim: In this study, our goal was to study the inhibition of nicotine metabolism by P450 2A6, as a means for
reduction in tobacco use and consequently the prevention of smoking-related cancers. Nicotine, a phytochemical,
is an addictive stimulant, responsible for the tobacco-dependence in smokers. Many of the other phytochemicals in
tobacco, including polycyclic aromatic hydrocarbons, N-nitrosamines, and aromatic amines, are potent systemic
carcinogens. Tobacco smoking causes about one of every five deaths in the United States annually. Nicotine
plasma concentration is maintained by the smokers’ smoking behavior within a small range. Nicotine is
metabolized by cytochrome P450s 2A6 and 2A13 to cotinine. This metabolism causes a decrease in nicotine
plasma levels, which in turn leads to increased tobacco smoking, and increased exposure to the tobacco
carcinogens.

Methods: Using the phytochemical nicotine as a lead structure, and taking its interactions with the P450 2A6
binding pocket into consideration, new pyridine derivatives were designed and synthesized as potential selective
mechanism-based inhibitors for this enzyme.

© The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing,
adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as
long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and
indicate if changes were made.

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