Antitumour activity of synthetic curcuminoid analogues (1,7-diaryl-1,6-heptadiene-3,5-diones) and their copper complexes

Abstract

Four new curcuminoid analogues, 1,7-bis(4-hydroxyphenyl)-1,6-heptadiene-3,5-dione, 1a; 1,7-di(2-furyl)-1,6-heptadiene-3,5-dione, 1b; 1,7-di(2-naphthyl)-1,6-heptadiene-3,5-dione, 1c; 1,7-bis(2-chlorophenyl)-1,6-heptadiene-3,5-dione, 1d; and their copper(II) complexes of ML2 stoichiometry were synthesized and characterized by UV, IR, 1H NMR, ESR and mass spectral data. The compounds were investigated for their possible cytotoxic and antitumour activities. It was found that copper chelates are remarkably active compared with free curcuminoid analogues. All the compounds were found to be cytotoxic towards Ehrlich ascites carcinoma cells and cultured L929 (lung fibroblast cells). In the case of culture studies, concentrations needed for 50% cell death were around 5 µg/ml for copper complexes and 10 µg/ml for curcuminoid analogues. Copper complex of 1a with hydroxyl group in the phenyl ring was found to be most active towards L929cells (1 µg/ml produced 43.3 ± 1.3% cell death). Compound 1b, which possesses a furyl ring system, was found to show least activity towards increase in life span of tumour-bearing mice (increase in life span 39.31%). Copper chelates of all curcuminoid analogues showed a significant reduction (p < 0.001) of solid tumour volume in mice. Copyright © 2005 John Wiley & Sons, Ltd.