title: Biological and anti-inflammatory evaluation of two thiazole compounds in RAW cell line: potential cyclooxygenase-2 specific inhibitors.
abstract: The anti-inflammatory effect of two new thiazoles derivatives CX-32 (N-[4-(4-hydroxy-3-methoxyphenyl)-1,3-thiazol-2-yl]acetamide) and CX-35 (4-(2-amino-1,3-thiazol-4-yl)-2-methoxyphenol), was investigated in LPS-stimulated RAW 264.7 cell line. Synthesis, structure analysis and purity of these compounds were evaluated by high performance liquid chromatography, H1 NMR, and C13 NMR. Assessment of CX-32 and CX-35 inhibitory effect on cyclooxygenase-2 (COX-2) activity was achieved by incubating LPS-activated RAW cells with 25 μM, 50 μM or 100 μM of CX-32 or CX-35 respectively. Levels of secreted PGE2 were evaluated by enzyme immunoassay (EIA) and levels of COX-2 protein were measured by western blot. Finally, cell viability experiments were undertaken to assess the toxicity of each compound. Treatment of LPS-activated RAW cells with 25 μM, 50 μM, or 100 μM of CX-35 or CX-32 respectively, prevented the production of prostaglandins, but was without effect on COX-2 protein levels. Moreover, CX-35 and CX-32 reduced PGE2 production to levels comparable to those obtained in LPS-activated RAW cells incubated with the selective COX-2 inhibitor NS 398. Furthermore, both CX-32 and CX-35 showed no toxic effects, since viability of non-treated Hela cells was similar to Hela cells incubated with either CX-35 or CX-32. Our data demonstrated that CX-32 and CX-35 significantly blocked prostaglandin production induced during inflammatory cellular stress, possibly acting through specific COX-2 inhibition; confirmation of this hypothesis requires further investigation.
authors.affiliation: Département de Chimie et Biochimie, Faculté des Sciences I. Laboratoire Génomique et Santé, Plateforme de Recherche en Sciences et Technologies, Université Libanaise, Hadath, Lebanon.
authors.forename: Eva
authors.initials: E
authors.lastname: Hamade
authors.forename: Aida
authors.initials: A
authors.lastname: Habib
authors.forename: Ali
authors.initials: A
authors.lastname: Hachem
authors.forename: Alaa H
authors.initials: AH
authors.lastname: Hussein
authors.forename: Malak
authors.initials: M
authors.lastname: Abbas
authors.forename: Taghreed
authors.initials: T
authors.lastname: Hirz
authors.forename: Mirvat
authors.initials: M
authors.lastname: Al Masri
authors.forename: Wissam H
authors.initials: WH
authors.lastname: Faour
mesh_terms: D000081:Acetamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006367:HeLa Cells; D006801:Humans; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects*; D051379:Mice; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C576659:4-(2-amino-1,3-thiazol-4-yl)-2-methoxyphenol; D000081:Acetamides; D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D008070:Lipopolysaccharides; C576660:N-(4-(4-hydroxy-3-methoxyphenyl)-1,3-thiazol-2-yl)acetamide; D013844:Thiazoles; D051546:Cyclooxygenase 2