Synthesis and Cytotoxic Activity of Novel Tetrahydrocurcumin Derivatives Bearing Pyrazole Moiety

Cancer is one of the major causes of death worldwide despite remarkable progress in understanding the mechanism of the disease and finding appropriate treatments to control the disease and prevent death. A large number of natural products have been reported to show anticancer and cancer preventive activities. One good example is the naturally occurring yellow pigment curcumin (Fig. 1 ), which was isolated from the rhizomes of the plant Curcuma longa Linn, a member of the ginger family (Zingiberaceae) [ 1 ]. In vitro and in vivo research as well as clinical studies have shown the anticancer effect of curcumin as an anticancer and chemo-prevention agent [ 2 , 3 ]. Curcumin has also been shown to act as a drug transporter-mediated MDR reversal agent [ 4 , 5 ]. Tetrahydrocurcumin (THC, Fig. 1 ) is a major metabolite derived from curcumin. Reduction of curcumin (Fig. 1 ) by endogenous reductase system leads to THC which plays an important role in curcumin-induced biological effects [ 6 ]. THC can also be chemically synthesized from curcumin by catalytic hydrogenation using PtO 2 or palladium as a catalyst [ 7 , 8 ]. THC has been reported to inhibit tumor metastasis [ 9 ] and tumor angiogenesis in nude mice [ 10 ]. In 2007, Limtrakul and his coworkers demonstrated that THC acted as a MDR modulator when combined with other chemotherapeutics [ 11 ]. Furthermore, THC has protective effect on renal damage resulted from chemotherapy such as cisplatin for the treatment of cancer [ 12 ]. In addition to anticancer activity, THC displayed potent antioxidant activity [ 13 ], antidiabetic, anti-inflammatory, antiatherosclerotic and antihepatotoxic effects [ 14 ].