Antiinflammatory properties of a hydroperoxide compound, structurally related to acetylsalicylic acid

  title={Antiinflammatory properties of a hydroperoxide compound, structurally related to acetylsalicylic acid},
  author={J. Killackey and B. Killackey and I. Cerskus and R. Philp},
Abstract3-Hydroperoxy-3-methylphthalide (3-HMP), a structural analog of acetylsalicylic acid (ASA), was found to have some antiinflammatory properties which are distinct from those of ASA. 3-HMP inhibits human platelet aggregation and ATP release in response to low concentrations of collagen but is less effective than ASA. 3-HMP inhibits prostaglandin and thromboxane production from exogenous [14C]arachidonic acid by human platelet lysates in vitro and does so at lower concentrations than ASA… Expand
Cyclic nucleotide phosphodiesterase inhibition by a benzoic acid derivative
It is proposed that the potent anti-inflammatory effects of 3-MP, which differ from those of ASA, are mediated through the inhibition of the cyclic nucleotide PDE system. Expand
Mononuclear phagocytes in the pathogenesis of neurodegenerative diseases
Common functions of brain MP in neuroimmunity link highly divergent diseases (for example, human immunodeficiency virus type-one associated dementia, Alzheimer's disease and Parkinson's disease). Research seeks to harness MP inflammatory processes with the intent of developing therapeutic interventions that block neurodegenerative processes and improve the quality of life in affected people. Expand
Asborin: The Carbaborane Analogue of Aspirin
Asborin, the carbaborane analogue of aspirin, was obtained by a high‐yield synthetic procedure and proved to be an active cyclooxygenase (COX) inhibitor (H: white, B: beige, C: gray, O: blue).


A new approach to anti-inflammatory drugs.
2-pyrazoline inhibits both pathways of arachidonic acid metabolism in vitro and causes a dose-dependent reduction in carrageenin-induced oedema in the rat paw, and BW755C reduces prostaglandin concentration in inflammatory exudates and has a significantly greater effect on leukocyte migration than indomethacin. Expand
Regulation of arachidonate-induced platelet aggregation by the lipoxygenase product, 12-hydroperoxyeicosatetraenoic acid.
The data suggest that 12-HPETE formation may regulate platelet aggregation and secretion and that its primary effect, at low concentrations, is inhibition of endoperoxide-induced responses and that at higher concentrations 12- HPETE also inhibits arachidonic acid metabolism. Expand
Effect of three nonsteroidal anti-inflammatory agents on platelet function and prostaglandin synthesis in vitro.
Abstract Effects on platelet aggregation in citrated, human, platelet-rich plasma (PRP) of nonsteroidal anti-inflammatory agents naproxen (Nap.), ibuprofen (Ib.) and aspirin (ASA) showed that theExpand
Application of imidazole as a selective inhibitor thromboxane synthetase in human platelets.
The results illustrate the utility of imidazole as a pharmacological tool and demonstrate the two unique and dissociable properties of the endoperoxides themselves--their ability to aggregate platelets and their enzymatic conversion to the potent vasoconstrictor thromboxane. Expand
Structure-activity studies of aspirin and related compounds on platelet aggregation, arachidonic acid metabolism in platelets and artery, and arterial prostacyclin activity.
A cyclical derivative, 3-methylphthalide (3-MP), inhibited both platelet function and PGI2 synthesis although it did not inhibit cyclo-oxygenase activity, suggesting a novel mechanism of action. Expand
Prostaglandin endoperoxides. Novel transformations of arachidonic acid in human platelets.
  • M. Hámberg, B. Samuelsson
  • Chemistry, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 1974
The almost exclusive transformation of the endoperoxide structure into non-prostaglandin derivatives supports the hypothesis that the end operoxides can participate directly and not by way of the classical prostaglandins in regulation of cell functions. Expand
Transformation of arachidonic acid and homo-gamma-linolenic acid by rabbit polymorphonuclear leukocytes. Monohydroxy acids from novel lipoxygenases.
Addition of arachidonic acid and homo-gamma-linolenic acid to a suspension of rabbit peritoneal neutrophils led to the synthesis of 5-L-hydroxy-6,8,11,14-eicosatetraenoic acid and 8- L-hydroxyl group alpha to a pair of conjugated cis/trans double bonds suggested that they were formed by action of lipoxygenease(s). Expand
Unique aspects of the modulation of human neutrophil function by 12-L-hydroperoxy-5,8,10,14-eicosatetraenoic acid.
12-OOHETE is more potent than 12-OHETE in the stimulation of some human neutrophil functions and in the elevation of the cellular concentration of cGMP, and may activate neutrophils by pathways not available to 12- OHETE. Expand
Antirheumatic Drug Effects on Neutrophil Response to Chemotactic Factors: A Comparison of Analytical Techniques 1
  • R. Turner, J. Johnson, E. Semble
  • Chemistry, Medicine
  • Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine
  • 1983
The results indicate that the leukotactic index may be a more sensitive technique for quantitating neutrophil migration in response to chemotactic factors and may therefore provide useful additional information for determining the effects of antirheumatic drugs on this important neutrophils function. Expand
Inhibition of human platelet aggregation by S-nitrosothiols. Heme-dependent activation of soluble guanylate cyclase and stimulation of cyclic GMP accumulation.
Data from this study are consistent with the hypothesis that S-nitrosothiols could serve as active intermediates in the inhibitory action of sodium nitroprusside, nitric oxide, and related nitrogen oxides on platelet aggregation. Expand