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Aryl bis(diazeniumdiolates): potent inducers of S-glutathionylation of cellular proteins and their in vitro antiproliferative activities.

Abstract：

:A number of bis(diazeniumdiolates) that we designed to release up to 4 mol of nitric oxide (NO) and that are structural analogues of the NO prodrug and anticancer lead compound O(2)-{2,4-dinitro-5-[4-(N-methylamino)benzoyloxy]phenyl} 1-(N,N-dimethylamino)diazen-1-ium-1,2- diolate (PABA/NO) were synthesized and studied. A majority of these compounds yielded higher levels of NO, were better inhibitors of proliferation of a number of cancer cell lines, and more rapidly induced substantially increased levels of S-glutathionylation of cellular proteins in comparison with PABA/NO. In most cases, the antiproliferative activity and extents of S-glutathionylation correlated well with levels of intracellular NO release. We report bis(diazeniumdiolates) to be a class of S-glutathionylating agents with potent antiproliferative and S-glutathionylating activity.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Andrei D,Maciag AE,Chakrapani H,Citro ML,Keefer LK,Saavedra JE

doi

10.1021/jm800831y

subject

Has Abstract

pub_date

2008-12-25 00:00:00

pages

7944-52

issue

24

eissn

0022-2623

issn

1520-4804

pii

10.1021/jm800831y

journal_volume

51

pub_type

杂志文章

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