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Enhanced topoisomerase II-induced DNA breaks and free radical production by a new anthracycline with potent antileukemic activity.

Abstract：

:In a previous study we reported that a new anthracycline derivative (moflomycin) exhibited a higher antileukemic activity compared to other anthracyclines, such as daunorubicin and doxorubicin. To explain the superior antileukemic effect of moflomycin and to disclose a possible structure-activity relationship, we investigated the three main mechanisms by which anthracyclines are though to exert their antitumor effect: DNA binding, free radical production and topoisomerase II inhibition. The DNA interaction was assessed both by DNA binding and DNA unwinding assays, free radical generation was studied by electron spin resonance, and topoisomerase II interaction by analysis of the stimulation of enzyme-induced DNA breaks. The results showed a higher free radical production and a greater stimulation of topoisomerase II-mediated DNA cleavage by moflomycin than doxorubicin, associated with a lower DNA affinity. The different biochemical characteristics of moflomycin, particularly its interaction with topoisomerase II, are related to the structural modifications performed on the chromophore. These properties, associated with a higher stability of the molecule induced by the presence of an iodine atom on the sugar moiety, are probably responsible for the higher antileukemic activity of this compound.

journal_name

Leuk Res

journal_title

Leukemia research

authors

Andrivon W,Saucier JM,Auclair C,Monneret C,Florent JC,Guillosson JJ,Nafziger J

doi

10.1016/0145-2126(95)00155-7

subject

Has Abstract

pub_date

1996-02-01 00:00:00

pages

119-26

issue

2

eissn

0145-2126

issn

1873-5835

pii

0145212695001557

journal_volume

20

pub_type

杂志文章

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