Open AccessNovel Copper(II) Complex with a 4-Acylpyrazolone Derivative and Coligand Induce Apoptosis in Liver Cancer Cells
Author(s) -
Marhaba Nurmamat,
Haili Yan,
Wang Ru,
Huixin Zhao,
Yanhong Li,
Xiaojing Wang,
Kaidirye Nurmaimaiti,
Tamasha Kurmanjiang,
Difang Luo,
Jumagul Baodi,
Guancheng Xu,
Jinyu Li
Publication year - 2021
Publication title -
acs medicinal chemistry letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.065
H-Index - 66
ISSN - 1948-5875
DOI - 10.1021/acsmedchemlett.0c00680
Subject(s) - apoptosis , chemistry , endoplasmic reticulum , ic50 , stereochemistry , cisplatin , cancer cell , microbiology and biotechnology , cancer research , biochemistry , biology , medicine , cancer , in vitro , chemotherapy
A novel pyrazolone-based copper complex [CuL(phen)(CH 3 OH)][CuL(phen)]·CH 3 CH 2 OH·CH 3 OH (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)(CH 3 OH)] and [CuL(phen)]:Cu1 2+ center with six coordination mode and Cu2 2+ center with five coordination mode. The growth of BEL-7404 cells and H22 cells was significantly inhibited by P-FAH-Cu-phen with IC 50 values of 1.175 μg/mL and 1.097 μg/mL, respectively, which were much lower than IC 50 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.