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Probing cytochrome P450-mediated activation with a truncated azinomycin analogue
Vinader, Victoria Sadiq, Maria Huang, M.Y. Elsalem, Lina M.I. Cui, H.J. Searcey, M.
Vinader, Victoria
Sadiq, Maria
Huang, M.Y.
Elsalem, Lina M.I.
Cui, H.J.
Searcey, M.
Publication Date
2015
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(c) 2015 Royal Society of Chemistry. Full-text reproduced in accordance with the publisher's self-archiving policy.
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Yes
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openAccess
Accepted for publication
14/10/2014
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Abstract
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.
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Accepted manuscript
Citation
Vinader V, Sadiq M, Sutherland M et al (2015) Probing cytochrome P450-mediated activation with a truncated azinomycin analogue. MedChemComm. 6(1): 187-191.
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Article