Probing cytochrome P450-mediated activation with a truncated azinomycin analogue
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2015Author
Vinader, VictoriaSadiq, 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
Keyword
Antitumor antibioticsSequence selectivity
Colon-cancer
cyp2w1
DNA
Cytotoxicity
Expression
Mechanism
Epoxide
Liver
Rights
(c) 2015 Royal Society of Chemistry. Full-text reproduced in accordance with the publisher's self-archiving policy.Peer-Reviewed
YesOpen Access status
openAccess
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Show full item recordAbstract
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.Version
Accepted manuscriptCitation
Vinader V, Sadiq M, Sutherland M et al (2015) Probing cytochrome P450-mediated activation with a truncated azinomycin analogue. MedChemComm. 6(1): 187-191.Link to Version of Record
https://doi.org/10.1039/c4md00411fType
Articleae974a485f413a2113503eed53cd6c53
https://doi.org/10.1039/c4md00411f