Diaryl-dithiolanes and -isothiazoles: COX-1/COX-2 and 5-LOX-inhibitory, OH scavenging and anti-adhesive activities
| Autor: | Holger Ulbrich, Andreas Mattern, Michael Scholz, Gerd Dannhardt, Oliver Soehnlein, Lennart Lindbom |
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| Rok vydání: | 2009 |
| Předmět: |
Neutrophils
Clinical Biochemistry Macrophage-1 Antigen Pharmaceutical Science Peritonitis Pharmacology Biochemistry Mice In vivo Drug Discovery Cell Adhesion Animals Cyclooxygenase Inhibitors Lipoxygenase Inhibitors Sulfhydryl Compounds Cell adhesion Molecular Biology biology Hydroxyl Radical Chemistry Anti-Inflammatory Agents Non-Steroidal Organic Chemistry In vitro toxicology Biological activity Free Radical Scavengers Adhesion In vitro Thiazoles Cyclooxygenase 2 Arachidonate 5-lipoxygenase Cyclooxygenase 1 biology.protein Molecular Medicine Cyclooxygenase |
| Zdroj: | Bioorganic & Medicinal Chemistry. 17:558-568 |
| ISSN: | 0968-0896 |
| Popis: | Three series of non-steroidal anti-inflammatory drugs (NSAIDs) inhibiting the cyclooxygenase/5-lipoxygenase (COX/5-LOX) pathways as such as formation of hydroxyl radicals and adhesion were prepared: 4,5-diaryl isothiazoles, 4,5-diaryl 3H-1,2-dithiole-3-thiones and 4,5-diaryl 3H-1,2-dithiole-3-ones. The aim of the present study was to develop substances which can intervene into the inflammatory processes via different mechanisms of action as multiple target non-steroidal anti-inflammatory drugs (MTNSAIDs) with increased anti-inflammatory potential. The current lead 11a was evaluated in COX-1/2, 5-LOX and (*)OH scavenging in vitro assays and in a static adhesion assay where it proved to inhibit adhesion. Moreover, 11a treatment attenuated expression of macrophage adhesion molecule-1 (Mac-1) on extravasated polymorphonuclear leukocytes (PMNs) which indicates that the activation was reduced. The assays used are predictive for the in vivo efficacy of test compounds as shown for 11a in a peritonitis model of acute inflammation in mice. Thus, the novel 5-LOX/COX and (*)OH inhibitor 11a possesses anti-inflammatory activity that, in addition to COX/5-LOX inhibition, implicates effects on leukocyte-endothelial interactions. |
| Databáze: | OpenAIRE |
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