title: Synthesis and inhibitory activity of dimethylamino-chalcone derivatives on the induction of nitric oxide synthase.
abstract: A series of nine dimethylamino-chalcone derivatives (1,3-diaryl-propenones) was synthesized and screened as potential inhibitors of NO and PGE(2) production in the RAW 264.7 macrophage cell line. 4-Dimethylamino-2',5'-dimethoxychalcone (6) was found to be the most potent and dual inhibitor (IC(50s) in the submicromolar range) of NO and PGE(2) production. 2',6'-Dimethoxylation appeared to be an effective requirement for selective and potent inhibition of nitric oxide synthase induction as it was confirmed by Western blot analysis. Chalcone (6) at 25 mg kg(-1) by oral route, inhibited significantly the formation of oedema in the carrageenan-induced model of inflammation in mice.
authors.affiliation: Departamento de Farmacología, Universidad de Valencia, Facultad de Farmacia, Av. V. Andrés Estelles s/n, 46100 Burjassot, Valencia, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Rojas
authors.forename: José N
authors.initials: JN
authors.lastname: Domínguez
authors.forename: Jaime E
authors.initials: JE
authors.lastname: Charris
authors.forename: Gricela
authors.initials: G
authors.lastname: Lobo
authors.forename: Miguel
authors.initials: M
authors.lastname: Payá
authors.forename: M Luisa
authors.initials: ML
authors.lastname: Ferrándiz
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology; D002460:Cell Line; D002599:Chalcone / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D004123:Dimethylamines / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D004353:Drug Evaluation, Preclinical; D004487:Edema / Q000188:drug therapy / Q000517:prevention & control; D004790:Enzyme Induction / Q000187:drug effects; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D013329:Structure-Activity Relationship
chemical_list: D000893:Anti-Inflammatory Agents; D004123:Dimethylamines; D002599:Chalcone; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D015232:Dinoprostone