Probing cytochrome P450-mediated activation with a truncated azinomycin analogue

Vinader, Victoria, Sadiq, Maria, Sutherland, Mark, Huang, Menying, Loadman, Paul, Elsalem, Lina, Shnyder, Steven, Cui, Hongjuan, Afarinkia, Kamyar, Searcey, Mark, Patterson, Laurence and Pors, Klaus (2015) Probing cytochrome P450-mediated activation with a truncated azinomycin analogue. MedChemComm, 6. pp. 187-191. ISSN 2040-2511

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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.

Item Type: Article
Uncontrolled Keywords: prodrug ,azinomycin,cytochrome p-450 cyp1a1
Faculty \ School: Faculty of Science > School of Pharmacy
Depositing User: Pure Connector
Date Deposited: 17 Apr 2015 14:04
Last Modified: 16 Jul 2021 23:50
DOI: 10.1039/C4MD00411F

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