Synthesis and inhibitory activity of dimethylamino-chalcone derivatives on the induction of nitric oxide synthase.
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.
Rojas
Javier
J
Departamento de Farmacología, Universidad de Valencia, Facultad de Farmacia, Av. V. Andrés Estelles s/n, 46100 Burjassot, Valencia, Spain.
Domínguez
José N
JN
Charris
Jaime E
JE
Lobo
Gricela
G
Payá
Miguel
M
Ferrándiz
M Luisa
ML
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
D000893:Anti-Inflammatory Agents; D004123:Dimethylamines; D002599:Chalcone; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D015232:Dinoprostone