Yes / A deactivated alkene precursor (IC50=81 mu M) to the azinomycin epoxide natural product can be bioactivated by several cytochromes P450 (CYP) to generate antiproliferative metabolites with increased potency (IC50=1-30 mu M) 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.
| Identifer | oai:union.ndltd.org:BRADFORD/oai:bradscholars.brad.ac.uk:10454/9419 |
| Date | 2014 October 1922 |
| Creators | Vinader, Victoria, Sadiq, Maria, Sutherland, Mark, Huang, M.Y., Loadman, Paul, Elsalem, Lina M.I., Shnyder, Steven, Cui, H.J., Afarinkia, Kamyar, Searcey, M., Patterson, Laurence H., Pors, Klaus |
| Source Sets | Bradford Scholars |
| Language | English |
| Detected Language | English |
| Type | Article, Accepted manuscript |
| Rights | (c) 2015 Royal Society of Chemistry. Full-text reproduced in accordance with the publisher's self-archiving policy., Unspecified |
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