Aryl Bis(diazeniumdiolates): Potent Inducers of S-Glutathionylation of Cellular Proteins and Their in Vitro Antiproliferative Activities
- 18 November 2008
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 51 (24), 7944-7952
- https://doi.org/10.1021/jm800831y
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 O2-{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.Keywords
This publication has 47 references indexed in Scilit:
- Synthesis, nitric oxide release, and anti-leukemic activity of glutathione-activated nitric oxide prodrugs: Structural analogues of PABA/NO, an anti-cancer lead compoundBioorganic & Medicinal Chemistry, 2008
- Synthesis and in vitro anti-leukemic activity of structural analogues of JS-K, an anti-cancer lead compoundBioorganic & Medicinal Chemistry Letters, 2008
- Nitric Oxide Prodrugs: Diazeniumdiolate Anions of Hindered Secondary AminesOrganic Letters, 2007
- Glutathionylation pathways in drug responseCurrent Opinion in Pharmacology, 2007
- Mechanisms of reversible protein glutathionylation in redox signaling and oxidative stressCurrent Opinion in Pharmacology, 2007
- JS-K, a GST-activated nitric oxide generator, induces DNA double-strand breaks, activates DNA damage response pathways, and induces apoptosis in vitro and in vivo in human multiple myeloma cellsBlood, 2007
- Piperazine as a Linker for Incorporating the Nitric Oxide-Releasing Diazeniumdiolate Group into Other Biomedically Relevant Functional MoleculesThe Journal of Organic Chemistry, 1999
- Structure, Catalytic Mechanism, and Evolution of the Glutathione TransferasesChemical Research in Toxicology, 1997
- Glutathione S‐Transferases: Structure and Mechanism of an Archetypical Detoxication EnzymePublished by Wiley ,1994
- The Reaction of Nitrogen(II) Oxide with Various Primary and Secondary AminesJournal of the American Chemical Society, 1961