Doxorubicin-3'-NH-oestrone-17-oxime-ethyl-carbonyl, a doxorubicin-oestrone conjugate that does not redox cycle in rat liver microsomes.
In summary doxorubicin-3'-NH-oestrone-17-oximethyl-carbonyl (Dox-Oes) is a covalent adduct of the anthracycline antitumor agent doxorubicin and oestrogen. Dox-Oes does not generate free radicals in rat liver microsomes as detected by electron spin resonance spectroscopy or redox cycle as shown by lack of superoxide anion formation and NADPH oxidation. Furthermore Dox-Oes actually inhibits free radical formation by doxorubicin used in equimolar amounts. The lack of free radical formation by doxorubicin when covalently linked to oestrone supports the development of Dox-Oes as a non-cardiotoxic derivative whilst potentially improving its targeting to oestrogen positive breast tumour cells.
Hartman
N G
NG
University of Cambridge, Department and MRC Centre of Clinical Oncology and Radiotherapeutics, U.K.
Patterson
L H
LH
Workman
P
P
Suarato
A
A
Angelucci
F
F
D000818:Animals; D002478:Cells, Cultured; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004970:Estrone / Q000031:analogs & derivatives* / Q000494:pharmacology; D005609:Free Radicals; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D051381:Rats; D013481:Superoxides / Q000032:analysis
D005609:Free Radicals; D013481:Superoxides; D004970:Estrone; D009249:NADP; D004317:Doxorubicin