ArticleBioorganic & medicinal chemistry2007
O2-acetoxymethyl-protected diazeniumdiolate-based NSAIDs (NONO-NSAIDs): synthesis, nitric oxide release, and biological evaluation studies.
Article in Bioorganic & medicinal chemistry, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed.
- Hybrid/Chimera Drugs - Part 1 - Drug Hybrids Affecting Diseases of the Central Nervous System.Current medicinal chemistry · 2025Review
- Fifty Years of Diazeniumdiolate Research: A Tribute to Dr. Larry K. Keefer.Critical reviews in oncogenesis · 2023Article
- Opportunities for Nitric Oxide in Potentiating Cancer Immunotherapy.Pharmacological reviews · 2022Review
- The evolving landscape for cellular nitric oxide and hydrogen sulfide delivery systems: A new era of customized medications.Biochemical pharmacology · 2020Review
- Combination of nitric oxide and drug delivery systems: tools for overcoming drug resistance in chemotherapy.Journal of controlled release : official journal of the Controlled Release Society · 2017Review
- Therapeutic Delivery of HJournal of the American Chemical Society · 2016Article
- Synthesis and chemical and biological comparison of nitroxyl- and nitric oxide-releasing diazeniumdiolate-based aspirin derivatives.Journal of medicinal chemistry · 2013Article
- Effects of nitric oxide-releasing nonsteroidal anti-inflammatory drugs (NONO-NSAIDs) on melanoma cell adhesion.Toxicology and applied pharmacology · 2012Article
- Nitroxide derivatives of non-steroidal anti-inflammatory drugs exert anti-inflammatory and superoxide dismutase scavenging properties in A459 cells.British journal of pharmacology · 2012Article
- Nitric Oxide-Releasing Hybrid Drugs Target Cellular Processes Through S-Nitrosylation.Forum on immunopathological diseases and therapeutics · 2012Article
- Anti-Inflammatory Drug Design Using a Molecular Hybridization Approach.Pharmaceuticals (Basel, Switzerland) · 2011Review
- Structurally Diverse Nitric Oxide-Releasing Poly(propylene Imine) Dendrimers.Chemistry of materials : a publication of the American Chemical Society · 2011Article
- Synthesis of N-arylidene-2-(2-Phenoxyphenyl) Acetohydrazides as Anti-Inflammatory Agents.Iranian journal of pharmaceutical research : IJPR · 2011Article
- Nanoprodrugs of NSAIDs: Preparation and Characterization of Flufenamic Acid Nanoprodrugs.Journal of drug delivery · 2011Article
- Comparison between 3-Nitrooxyphenyl acetylsalicylate (NO-ASA) and O2-(acetylsalicyloxymethyl)-1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate (NONO-ASA) as safe anti-inflammatory, analgesic, antipyretic, antioxidant prodrugs.The Journal of pharmacology and experimental therapeutics · 2010Article
- (1S,4S,5S,8R)-8-Nitro-oxy-2,6-dioxa-bicyclo-[3.3.0]octan-4-yl 3,4,5-triacetoxy-benzoate.Acta crystallographica. Section E, Structure reports online · 2009Article
- Mechanistic studies on the reaction between R2N-NONOates and aquacobalamin: evidence for direct transfer of a nitroxyl group from R2N-NONOates to cobalt(III) centers.Angewandte Chemie (International ed. in English) · 2009Article
- NO-donating NSAIDs and cancer: an overview with a note on whether NO is required for their action.Nitric oxide : biology and chemistry · 2008Review
- Synthesis, nitric oxide release, and anti-leukemic activity of glutathione-activated nitric oxide prodrugs: Structural analogues of PABA/NO, an anti-cancer lead compound.Bioorganic & medicinal chemistry · 2008Article
- Synthesis and in vitro anti-leukemic activity of structural analogues of JS-K, an anti-cancer lead compound.Bioorganic & medicinal chemistry letters · 2008Article
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
A novel group of O2-acetoxymethyl-protected diazeniumdiolate-based non-steroidal anti-inflammatory prodrugs (NONO-NSAIDs) were synthesized by esterifying the carboxylate group of aspirin, ibuprofen, or indomethacin with O2-acetoxymethyl 1-[N-(2-hydroxyethyl)-N-methylamino]diazeniumdiolate. The resulting nitric oxide (*NO)-releasing prodrugs (7-9) did not exhibit in vitro cyclooxygenase (COX) inhibitory activity against the COX-1 and COX-2 isozymes (IC50s>100 microM). In contrast, prodrugs 7 and 8 significantly decreased carrageenan-induced rat paw edema showing enhanced in vivo anti-inflammatory activities (ID50's=552 and 174 micromol/kg, respectively) relative to those of the parent NSAIDs aspirin (ID50=714 micromol/kg) and ibuprofen (ID50=326 micromol/kg). The rate of porcine liver esterase-mediated *NO release from prodrugs 7-9 (2 mol of *NO/mol of test compound in 0.6-6.5 min) was substantially higher compared to that observed without enzymatic catalysis (about 1 mol of *NO/mol of test compound in 40-48 h). These incubation studies suggest that both *NO and the parent NSAID would be released upon in vivo activation (hydrolysis) by esterases. Data acquired in an in vivo ulcer index (UI) assay showed that NONO-aspirin (UI=0.8), NONO-indomethacin (UI=1.3), and particularly NONO-ibuprofen (UI=0) were significantly less ulcerogenic compared to the parent drugs aspirin (UI=57), ibuprofen (UI=46) or indomethacin (UI=34) at equimolar doses. The release of aspirin and *NO from the NONO-aspirin (7) prodrug constitutes a potentially beneficial property for the prophylactic prevention of thrombus formation and adverse cardiovascular events such as stroke and myocardial infarction.
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