Novel Copper(II) Complex with a 4-Acylpyrazolone Derivative and Coligand Induce Apoptosis in Liver Cancer Cells
Marhaba Nurmamat, Haili Yan, Ru Wang, Huixin Zhao, Yanhong Li, Xiao‐Jing Wang, Kaidirye Nurmaimaiti, Tamasha Kurmanjiang, Difang Luo, Jumagul Baodi, Guan‐Cheng Xu, Jinyu Li
Abstract
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.