Novel Copper(II) Complex with a 4-Acylpyrazolone Derivative and Coligand Induce Apoptosis in Liver Cancer Cells

A novel pyrazolone-based copper complex [CuL(phen)(CH₃OH)][CuL(phen)]·CH₃CH₂OH·CH₃OH (P-FAH-Cu-phen) was synthesized and characterized. The asymmetric structural unit of P-FAH-Cu-phen was composed of two independent complex units [CuL(phen)(CH₃OH)] and [CuL(phen)]:Cu1²⁺ center with six coordination mode and Cu2²⁺ center with five coordination mode. The growth of BEL-7404 cells and H22 cells was significantly inhibited by P-FAH-Cu-phen with IC₅₀ values of 1.175 μg/mL and 1.097 μg/mL, respectively, which were much lower than IC₅₀ of cisplatin for BEL-7404 cells (23.32 μg/mL) and H22 cells (27.5 μg/mL). P-FAH-Cu-phen induced cell cycle arrest at G2/M and apoptosis in BEL-7404 cells through mitochondria- and endoplasmic reticulum stress-associated pathways. Moreover, P-FAH-Cu-phen significantly suppressed the migration of BEL-7404 cells and the tumor growth in H22 tumor mouse model without severe side effects and improved the survival of tumor mice. The results suggested that P-FAH-Cu-phen might be a potential drug candidate for the treatment of live cancer.