Synthesis and inhibitory activity of dimethylamino-chalcone derivatives on the induction of nitric oxide synthase

Eur J Med Chem. 2002 Aug;37(8):699-705. doi: 10.1016/s0223-5234(02)01387-9.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / chemical synthesis*
  • Anti-Inflammatory Agents / pharmacology
  • Cell Line
  • Chalcone / administration & dosage
  • Chalcone / chemical synthesis
  • Chalcone / pharmacology*
  • Dimethylamines / administration & dosage
  • Dimethylamines / chemical synthesis
  • Dimethylamines / pharmacology
  • Dinoprostone / antagonists & inhibitors
  • Dinoprostone / biosynthesis
  • Drug Evaluation, Preclinical
  • Edema / drug therapy
  • Edema / prevention & control
  • Enzyme Induction / drug effects
  • Macrophages / cytology
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Mice
  • Nitric Oxide Synthase / antagonists & inhibitors*
  • Nitric Oxide Synthase / biosynthesis
  • Nitric Oxide Synthase Type II
  • Structure-Activity Relationship

Substances

  • Anti-Inflammatory Agents
  • Dimethylamines
  • Chalcone
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Dinoprostone