Probing cytochrome P450-mediated activation with a truncated azinomycin analogue

Autor:	Vinader, Victoria, Sadiq, Maria, Sutherland, Mark, Huang, M.Y., Loadman, Paul, Elsalem, Lina M.I., Shnyder, Steven, Cui, H.J., Afarinkia, Kamyar, Searcey, M., Patterson, Laurence H., Pors, Klaus
Jazyk:	angličtina
Rok vydání:	2015
Předmět:	Antitumor antibiotics Sequence selectivity Colon-cancer cyp2w1 DNA Cytotoxicity Expression Mechanism Epoxide Liver
Druh dokumentu:	Článek
DOI:	10.1039/c4md00411f
Popis:	Yes A deactivated alkene precursor (IC50=81 mu M) to the azinomycin epoxide natural product can be bioactivated by several cytochromes P450 (CYP) to generate antiproliferative metabolites with increased potency (IC50=1-30 mu M) 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.
Databáze:	Networked Digital Library of Theses & Dissertations
Externí odkaz:	http://hdl.handle.net/10454/9419 Zobrazit plný text záznamu