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Issue 1, 2015
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Probing cytochrome P450-mediated activation with a truncated azinomycin analogue

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Abstract

A deactivated alkene precursor (IC50 = 81 μM) to the azinomycin epoxide natural product can be bioactivated by several cytochromes P450 (CYP) to generate antiproliferative metabolites with increased potency (IC50 = 1–30 μM) in CHOwt cells. CYP1A1 and 3A4 were shown to generate exclusively the unnatural and the natural-configured azinomycin epoxide diastereoisomer respectively, while CYP1B1 produced both epoxides in a 3 : 1 mixture. The antiproliferative activity is linked to DNA damage as demonstrated using the comet assay.

Graphical abstract: Probing cytochrome P450-mediated activation with a truncated azinomycin analogue

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Publication details

The article was received on 15 Sep 2014, accepted on 14 Oct 2014 and first published on 22 Oct 2014


Article type: Concise Article
DOI: 10.1039/C4MD00411F
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Med. Chem. Commun., 2015,6, 187-191

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    Probing cytochrome P450-mediated activation with a truncated azinomycin analogue

    V. Vinader, M. Sadiq, M. Sutherland, M. Huang, P. M. Loadman, L. Elsalem, S. D. Shnyder, H. Cui, K. Afarinkia, M. Searcey, L. H. Patterson and K. Pors, Med. Chem. Commun., 2015, 6, 187
    DOI: 10.1039/C4MD00411F

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