Cu(II) complex of an estradiol derivative with potent anti-inflammatory properties

Arch Pharm (Weinheim). 1991 Sep;324(9):533-6. doi: 10.1002/ardp.2503240902.

Abstract

In the present study, the A-ring of estradiol was converted to an acetylsalicylic structure which was further complexed with Cu(II). The aim was to combine the anti-inflammatory properties of estrogens with those of Cu(II) complexes. Key intermediate of the synthesis was 2-formyl-estradiol (2) which was prepared in quantitative yield through reaction of the phenoxymagnesium bromide of estradiol with formaldehyde in the presence of HMPA. For a successful reaction, an excess of ethylmagnesium bromide was required, and the mechanism is discussed. The target complex 5 exhibited potent anti-inflammatory properties, comparable to those of indomethacin, in the carrageenan-induced rat paw edema. This biological activity was not due either to the steroidal ligand or to the complexed Cu(II) alone.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / chemical synthesis*
  • Anti-Inflammatory Agents / pharmacology
  • Aspirin / chemistry
  • Carrageenan
  • Copper / chemistry*
  • Edema / chemically induced
  • Edema / prevention & control
  • Estradiol / analogs & derivatives*
  • Estradiol / chemical synthesis
  • Estradiol / pharmacology
  • Male
  • Organometallic Compounds / chemical synthesis*
  • Organometallic Compounds / pharmacology
  • Rats
  • Rats, Inbred F344

Substances

  • Anti-Inflammatory Agents
  • Organometallic Compounds
  • tetrakis(3,17-diacetoxyestra-1,3,5(10)-trien-2-carboxylato)dicopper(II)
  • Estradiol
  • 3,17-diacetoxyestra-1,3,5(10)-trien-2-carboxylic acid
  • Copper
  • Carrageenan
  • Aspirin