Anti-inflammatory therapy is actually devolved to glucocorticoids which prevent the release of arachidonic acid from phospholipids and consequently its subsequent transformation into prostaglandins and leukotrienes. This activity explains in part why steroids are better anti-inflammatory agents than acetylsalicylic acid (ASA)-like drugs which only reduce prostaglandin production. Despite their superior therapeutic actions, there are many side effects associated with corticosteroids. Therefore in recent years, research of non-steroid dual inhibitors of prostaglandin and leukotriene production has been developed. The present paper investigates the pharmacological activity of such a new compound, CBS-1108 (2-acetylthiophene-2-thiazolylhydrazone), in comparison with dexamethasone, cyclooxygenase inhibitors (ASA and indomethacin) and reference dual inhibitors (nordihydroguaiaretic acid (NDGA) and 3-amino-1-(m-trifluoromethylphenyl)-2-pyrazoline (BW-755 C]. The two-pathway inhibitors and ASA-like drugs are similarly effective on paracentesis-induced disruption of the blood-aqueous barrier and on croton oil-induced ear edema. On the contrary in an animal model of leukocyte migration and on mast cell degranulation, NDGA and CBS-1108 are very active when the other tested compounds are inefficient.
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Rapid detection and characterization of minor reactive metabolites using stable-isotope trapping in combination with tandem mass spectrometry.
Rapid Commun Mass Spectrom
March 2006
Division of Drug Discovery, Johnson & Johnson Pharmaceutical Research & Development, LLC, Spring House, PA 19477, USA.
Stable-isotope trapping combined with mass spectrometry (MS) neutral loss scanning has recently been developed as a high-throughput method for the in vitro screening of major reactive metabolites. In fact, detection and identification of minor reactive metabolites are equally important since the minor metabolites, even though at low levels, may be highly reactive and also play an important role in drug-induced adverse reactions. In this study, 2-acetylthiophene, clozapine, troglitazone and 7-methylindole were selected as model compounds to further validate the advantages of this method for rapid detection and structural characterization of minor glutathione (GSH) adducts derived from reactive metabolites.
View Article and Find Full Text PDFAnti-inflammatory therapy is actually devolved to glucocorticoids which prevent the release of arachidonic acid from phospholipids and consequently its subsequent transformation into prostaglandins and leukotrienes. This activity explains in part why steroids are better anti-inflammatory agents than acetylsalicylic acid (ASA)-like drugs which only reduce prostaglandin production. Despite their superior therapeutic actions, there are many side effects associated with corticosteroids.
View Article and Find Full Text PDFCBS-1108, 2- acetylthiophene 2- thiazolyhydrazone , inhibits 5-lipoxygenase activity in polymorphonuclear leukocytes (PMNs) (IC50 = 2 X 10(-6) M), 12-lipoxygenase (IC50 = 9 X 10(-6) M) and cyclooxygenase (IC50 = 2 X 10(-6) M) in platelets. Inhibition of the two pathways of arachidonic acid cascade could lead to additional beneficial anti-inflammatory activity by comparison with classical aspirin-like drugs. In fact, only inhibitors of both cyclooxygenase and lipoxygenase such as NDGA and CBS-1108 inhibit leukocyte migration in an animal model of acute inflammatory response.
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