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Issue 12, 2016
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New hybrid bromopyridine-chalcones as in vivo phase II enzyme inducers: potential chemopreventive agents

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Abstract

Cancer prevention can be achieved by the administration of cancer chemopreventive agents (CCAs) that prevent, delay or reverse the carcinogenic process. CCAs that are able to induce detoxification enzymes, especially monofunctional phase II enzymes, have become an excellent therapeutic strategy. Herein, we report the synthesis of eighteen new potential CCAs, structurally designed to combine (naphtho)chalcone and (bromo)pyridine skeletons. After a selection process involving in vitro phase II induction studies, cytotoxicity against tumoral cells, mutagenicity (the Ames test), and capability for DNA strand breakage (the alkaline comet assay), compound 22, (E)-3-(2-bromopyridin-3-yl)-1-(2-hydroxyphenyl)-2-propen-1-one, was selected for animal studies. The in vivo proof of concept study for derivative 22 demonstrated that it was able to significantly increase the QR and GST activities in the liver, colon and mammary gland without significant induction of the phase I enzyme, CYP. Additionally, we found that for 22 and another in vitro QR activity inducer, (E)-1-(2-hydroxyphenyl)-3-(naphthalen-1-yl)-2-propen-1-one (compound 8), Nrf2 nuclear translocation is operative allowing the exertion of protective effects via the expression of downstream phase II enzymes.

Graphical abstract: New hybrid bromopyridine-chalcones as in vivo phase II enzyme inducers: potential chemopreventive agents

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Publication details

The article was received on 07 Aug 2016, accepted on 16 Sep 2016 and first published on 22 Sep 2016


Article type: Research Article
DOI: 10.1039/C6MD00456C
Citation: Med. Chem. Commun., 2016,7, 2395-2409
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    New hybrid bromopyridine-chalcones as in vivo phase II enzyme inducers: potential chemopreventive agents

    M. Cabrera, H. Cerecetto and M. González, Med. Chem. Commun., 2016, 7, 2395
    DOI: 10.1039/C6MD00456C

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