The synthesis and the biological activities of curcumin analogues

Abstract

Curcumin, the major bioactive constituent of turmeric, has been shown to possess a myriad of beneficial biological activities, including anti-cancer, anti-bacterial. Curcumin also stimulates cell growth, in particular that of olfactory ensheathing cells (OECs, for the treatment of spinal cord injury). Clinical applications for curcumin are, however, limited due to poor stability, poor bioavailability and its metabolic profile. Chemically modifying the structure of curcumin by synthesising analogues is one of many ways to overcome these drawbacks. In this study, forty-six curcumin analogues were synthesised using a newly developed microwave-assisted protocol involving the aldol condensation reaction of 7-carbon diketones with various substituted benzaldehydes. Thirteen pyrazole-containing curcumin derivatives were also synthesised. These analogues were screened for anti-prostate cancer and anti-bacterial activity, and also growth-promoting activity in OECs. Five lead compounds were identified; four curcumin analogues showed potent anti-prostate cancer activity in the submicromolar range and one other analogue displayed potent anti-bacterial activity in Gram-positive bacteria, with a novel mechanism of action. Four lead compounds were found to have similar (or reduced) stability to curcumin, and all five lead compounds are poorly water-soluble. Lead optimisation was attempted; the resulting compound had improved stability and water solubility but unfortunately, had no biological activity.