Effects of cyclohexanone analogues of curcumin on growth, apoptosis and NF-κB activity in PC-3 human prostate cancer cells.

Curcumin is a non-nutritive yellow pigment found in the spice turmeric, which is derived from the rhizome of the plant Curcuma longa Linn. Six cyclohexanone analogues of curcumin (A(1)-A(6)) were investigated for their effects on growth and apoptosis in PC-3 human prostate cancer cells. The ability of these compounds to inhibit NF-κB activity in PC-3 cells was also determined. Five out of the six curcumin analogues (A(2)-A(6)) had stronger inhibitory effects compared to curcumin on the growth of cultured PC-3 cells. Compounds A(2)-A(6) also had stronger stimulatory effects on apoptosis in PC-3 cells than curcumin, and these curcumin analogues more potently inhibited NF-κB activity than curcumin. The inhibitory effects of these compounds on NF-κB activity correlated with their effects on growth inhibition and apoptosis stimulation in PC-3 cells. The results of the present study provide a rationale for in vivo studies with A(2)-A(6) using suitable animal models of prostate cancer.

Antioxidation and tyrosinase inhibition of polyphenolic curcumin analogs.

A series of polyphenolic curcumin analogs were synthesized and their inhibitory effects on mushroom tyrosinase and the inhibition of 1,1-diphenyl-2-picryl-hydrazyl (DPPH) free radical formation were evaluated. The results indictated that the analogs possessing m-diphenols and o-diphenols exhibited more potent inhibitory activity on tyrosinase than reference compound rojic acid, and that the analogs with o-diphenols exhibited more potent inhibitory activity of DPPH free-radical formation than reference compound vitamin C. The inhibition kinetics, analyzed by Lineweaver-Burk plots, revealed that compounds B(2) and C(2) bearing o-diphenols were non-competitive inhibitors, while compounds B(11) and C(11) bearing m-diphenols were competitive inhibitors. In particular, representative compounds C(2) and B(11) showed no side effects at a dose of 2,000 mg/kg in a preliminary evaluation of acute toxicity in mice. These results suggest that such polyphenolic curcumin analogs might serve as lead compounds for further design of new potential tyrosinase inhibitors.