In vitro effects of E3040, a dual inhibitor of 5-lipoxygenase and thromboxane A(2) synthetase, on eicosanoid production
| Autor: | Kiyoshi Oketani, Koukichi Harada, Takashi Inoue, Naoki Nagakura |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Male
Thromboxane Leukotriene B4 Neutrophils Pyridines Indomethacin Pharmacology Dinoprostone chemistry.chemical_compound medicine Leukocytes Animals Humans Hydroxyurea Platelet Benzothiazoles Lipoxygenase Inhibitors Mesalamine Peritoneal Cavity Arachidonate 5-Lipoxygenase Sheep Leukotriene C4 biology Dose-Response Relationship Drug Zileuton Rats Inbred F344 Rats Sulfasalazine Thromboxane B2 Thiazoles chemistry Biochemistry Prostaglandin-Endoperoxide Synthases Arachidonate 5-lipoxygenase biology.protein Eicosanoids Methacrylates Thromboxane-A synthase Cyclooxygenase Thromboxane-A Synthase medicine.drug |
| Zdroj: | European journal of pharmacology. 422(1-3) |
| ISSN: | 0014-2999 |
| Popis: | In vitro pharmacological profiles of E3040, 6-hydroxy-5, 7-dimethyl-2-(methylamino)-4-(3-pyridylmethyl) benzothiazole were investigated. Against the 5-lipoxygenase activity of rat basophilic leukemia cells, E3040 and zileuton (a 5-lipoxygenase inhibitor) had an IC(50) of 0.23 and 0.93 microM, respectively. Against the thromboxane A(2) synthetase activity of human platelets, E3040 had an IC(50) of 0.01 microM, which was comparable to that of OKY-1581 (sodium (E)-3-[4-(3-pyridylmethyl) phenyl]-2-methylacrylate, a thromboxane A(2) synthetase inhibitor). Against cyclooxygenase activity of sheep seminal vesicles, E3040 showed no inhibition (IC(50),300 microM). Sulfasalazine and 5-aminosalicylic acid, therapeutic drugs for inflammatory bowel disease, inhibited 5-lipoxygenase activity with an IC(50) of 293 and 970 microM, respectively. Sulfasalazine inhibited thromboxane A(2) synthetase activity with an IC(50) of 20 microM. In rat peritoneal leukocytes, E3040 inhibited leukotriene B(4) and thromboxane B(2) production with an IC(50) of 0.17 and 0.24 microM, respectively. E3040 inhibited leukotriene B(4) production in human neutrophils and thromboxane B(2) production in human platelets (IC(50) of 0.21 and 0.09 microM, respectively). These results indicated that E3040 potently inhibited 5-lipoxygenase and thromboxane A(2) synthetase and blocked leukotriene B(4) and thromboxane B(2) production in rat peritoneal and human blood cells. |
| Databáze: | OpenAIRE |
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