期刊
JOURNAL OF MEDICINAL CHEMISTRY
卷 51, 期 24, 页码 7944-7952出版社
AMER CHEMICAL SOC
DOI: 10.1021/jm800831y
关键词
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资金
- NIH
- Intramural Research Program of the NIH
- National Cancer Institute
- Center for Cancer Research
- National Cancer Institute [N01-CO-12400]
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.
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