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 ORCID:, 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
UEA Research Groups: Faculty of Science > Research Groups > Medicinal Chemistry (former - to 2017)
Faculty of Science > Research Groups > Chemical Biology and Medicinal Chemistry (former - to 2021)
Depositing User: Pure Connector
Date Deposited: 17 Apr 2015 14:04
Last Modified: 21 Oct 2022 00:14
DOI: 10.1039/C4MD00411F


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