MedChemComm p. 187 - 191 (2015)
Update date:2022-08-03
Topics:
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
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. This journal is
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