Chemistry, biochemistry and selective cytotoxicity of curcumin analogues against human cancer cell lines

Several curcuminoids including curcumin have been identified from the rhizome of a common spice Curcuma longa (Zingaberaceae). These natural curcuminoids display several pharmacological activities including anticancer activity. We have synthesized a range of curcumin analogues with phenolic, thiophene, furanyl, ascorbyl, indole, naphthyl, haloaryl and alkoxyphenyl groups and have shown that from amongst these compounds alkoxyphenyl curcumins have higher potential as anticancer agents. The synthetic curcumin analogues (Cd1-Cd6) showed a dose-dependent anti-mitogenic activity against human colorectal (CCL218), breast (HTB26) and lung (HTB182) cancer cell lines with minimal effect on normal human fibroblast (CRL1554) (≤ 20%). Our results demonstrate that synthetic curcumin analogues exerted a potency order Cd5 (IC50 = 12.3 μg/ml) > Cd4 (IC50 = 23.46 μg/ml) > Cd2 (IC50 = 26.15 μg/ml) > Cd6 (IC50 = 28.3 μg/ml) > Cd1 (IC50 = 38.46 μg/ml) > curcumin (IC50 =53.3 μg/ml) against CCL218 and Cd4 (IC50 = 11.15μg/ml) > Cd5 (IC50 = 12.3 μg/ml) > curcumin(IC50 =13.3μg/ml) against HTB26 as well as Cd5 (IC50 = 13.85 μg/ml) > curcumin(IC50 = 18.3 μg/ml) against HTB182. These results indicate that Cd4 and Cd5 curcumin analogues exhibit the highest anti-proliferative activities toward all the tested cancer cell lines with minimal cytotoxicity on normal human fibroblast. Further in vitro and in vivo studies are warranted to evaluate the chemopreventive/chemotherapeutic potential of these derivatives and to understand the potential molecular mechanisms of their action.