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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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Supplementary files

Article information


Submitted
15 Sep 2014
Accepted
14 Oct 2014
First published
22 Oct 2014

Med. Chem. Commun., 2015,6, 187-191
Article type
Concise Article
Author version available

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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