title: Synthesis and biological evaluation of new benzo-thieno[3,2-d]pyrimidin-4-one sulphonamide thio-derivatives as potential selective cyclooxygenase-2 inhibitors.
abstract: The aim of this work was to evaluate the potential anti-inflammatory activity of eleven (5-15) new synthesized derivatives of benzo-thieno[3,2-d]pyrimidine on two cell models, namely human keratinocytes NCTC 2544 and mouse monocyte-macrophages J774. For the synthesis of test compounds an efficient approach was developed: the key isothiocyanate was prepared through a simple and ecological method using di-2-pyridyl thionocarbonate (DPT) in substitution of thiophosgene, a highly toxic agent, and the cyclization reaction of benzo-thiosemicarbazide derivates was performed through Wamhoff methods. This procedure can be a new alternative method economically and environmentally advantageous by the simplicity of procedure, reduction of isolation and purification steps, time, costs, and waste production. The potential anti-inflammatory activity of 5-15 was evaluated by determining the expression of cyclooxygenase (COX)-2, inducible NO synthase (iNOS), and intercellular adhesion molecule-1 (ICAM-1), and the release of prostaglandins (PG)E[Formula: see text] and interleukin-8 (IL-8). Our results demonstrate that the compounds 7, 10, 12, 13, 14, and 15 act as a potent inhibitor of COX-2, iNOS, ICAM-1 expression while also suppressing the production of PGE[Formula: see text] and IL-8 in human keratinocytes NCTC 2544 exposed to interferon-gamma (IFN-[Formula: see text]) and histamine and monocyte-macrophages J774 cells treated with lipopolysaccharides (LPS). In conclusion, some derivatives of benzo-thieno[3,2-d]pyrimidine could be developed as a novel class of anti-inflammatory agents.
authors.affiliation: Department of Pharmaceutical Sciences, University of Catania, V.le A. Doria 6, 95125 , Catania, Italy.
authors.forename: Mariarita
authors.initials: M
authors.lastname: Barone
authors.forename: Adriana Carol Eleonora
authors.initials: AC
authors.lastname: Graziano
authors.forename: Agostino
authors.initials: A
authors.lastname: Marrazzo
authors.forename: Pietro
authors.initials: P
authors.lastname: Gemmellaro
authors.forename: Andrea
authors.initials: A
authors.lastname: Santagati
authors.forename: Venera
authors.initials: V
authors.lastname: Cardile
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D006575:Heterocyclic Compounds, 3-Ring / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D007371:Interferon-gamma; D016209:Interleukin-8 / Q000096:biosynthesis / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D009000:Monocytes / Q000187:drug effects; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D011458:Prostaglandins E / Q000096:biosynthesis / Q000378:metabolism; D011744:Pyrimidinones / Q000138:chemical synthesis / Q000494:pharmacology*; D013876:Thiophenes / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D052246:Cyclooxygenase 2 Inhibitors; D006575:Heterocyclic Compounds, 3-Ring; D016209:Interleukin-8; D008070:Lipopolysaccharides; D011458:Prostaglandins E; D011744:Pyrimidinones; D013876:Thiophenes; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2