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.
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.
Original language | English |
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Pages (from-to) | 187-191 |
Number of pages | 5 |
Journal | MedChemComm |
Volume | 6 |
Early online date | 22 Oct 2014 |
DOIs | |
Publication status | Published - 2015 |
Keywords
- Prodrug
- Azinomycin
- Cytochrome P-450 CYP1A1
Profiles
-
Mark Searcey
- School of Pharmacy - Pro-Vice-Chancellor
- Norwich Institute for Healthy Aging - Member
Person: Research Centre Member, Academic, Teaching & Research