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.

• Authors: Daniela Andrei, Anna E Maciag, Harinath Chakrapani, Michael L Citro, Larry K Keefer, Joseph E Saavedra
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 51 Issue 24 Pg. 7944-52 (Dec 25 2008) ISSN: 1520-4804 [Electronic] United States
• PMID: 19053760 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural)

Chemical References

• Azo Compounds
• Nitric Oxide Donors
• Prodrugs
• diazeniumdiolate
• Nitric Oxide
• Glutathione

Topics

• Azo Compounds (chemistry, pharmacology)
• Cell Line, Tumor
• Cell Proliferation
• Chemistry, Pharmaceutical (methods)
• Drug Design
• Drug Screening Assays, Antitumor
• Glutathione (chemistry)
• HL-60 Cells
• Humans
• Inhibitory Concentration 50
• Models, Chemical
• Nitric Oxide (chemistry)
• Nitric Oxide Donors (chemistry)
• Prodrugs (chemistry)