Cu(II) complex of an estradiol derivative with potent anti-inflammatory properties.
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.
Spyriounis
D M
DM
Department of Pharmaceutical Chemistry, School of Pharmacy, University of Thessaloniki, Greece.
Rekka
E
E
Demopoulos
V J
VJ
Kourounakis
P N
PN
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001241:Aspirin / Q000737:chemistry; D002351:Carrageenan; D003300:Copper / Q000737:chemistry*; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D004958:Estradiol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D008297:Male; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344
D000893:Anti-Inflammatory Agents; D009942:Organometallic Compounds; C073107:tetrakis(3,17-diacetoxyestra-1,3,5(10)-trien-2-carboxylato)dicopper(II); D004958:Estradiol; C073106:3,17-diacetoxyestra-1,3,5(10)-trien-2-carboxylic acid; D003300:Copper; D002351:Carrageenan; D001241:Aspirin