Probing cytochrome P450-mediated activation with a truncated azinomycin analogue. Issue 1 (29th October 2014)

• Record Type: Journal Article
• Authors: Vinader, Victoria; Sadiq, Maria; Sutherland, Mark; Huang, Mengying; Loadman, Paul M.; Elsalem, Lina; Shnyder, Steven D.; Cui, Hongjuan; Afarinkia, Kamyar; Searcey, Mark; Patterson, Laurence H.; Pors, Klaus
• Is Part Of: MedChemComm. Volume 6:Issue 1(2015:Jan.)
• Page Start: 187
• Page End: 191
• Publication Date: 2014-10-29
• Subjects: Pharmaceutical chemistry -- Periodicals; 615.19
• DOI: 10.1039/c4md00411f
• Languages: English
• ISSNs: 2040-2503

Abstract

Abstract : Selective cytochrome P450 bioactivation of truncated azinomycin. Abstract : 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.