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 PtO₂ 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].

A large number of curcumin derivatives and analogues have been synthesized in order to improve its low bioavailability, pharmacological properties and therapeutic efficacy for the treatment of a number of diseases [15, 16]. In contrast, despite the great therapeutic potential THC has shown, so far few derivatives and analogues of THC have been synthesized in order to improve its biological activities [7, 17–21]. In fact, THC might be considered advantageous over curcumin as a starting material for structural modification in that the former is stable under physiological pH while the latter is not. A recent report suggests that curcumin is a highly improbable drug lead due to its instability, high reactivity and low bioavailability [22]. Here we choose THC as the staring material for preparing pyrazole derivatives.

In the past few decades, pyrazole and its derivatives have been attracted considerable attention due to the growing importance of their medical uses, particularly in Oncology. For example, some pyrazole derivatives have been shown to be highly potent against human breast [23], lung [24] and cervical [25] cancer cells. In the present study we have synthesized a group of new pyrazole derivatives of THC (Fig. 1) as potential anticancer agents. Replacing the 1,3-diketone by a pyrazole group may lead to increased anticancer activity.