Nurmamat Marhaba, Yan Haili, Wang Ru, Zhao Huixin, Li Yanhong, Wang Xiaojing, Nurmaimaiti Kaidirye, Kurmanjiang Tamasha, Luo Difang, Baodi Jumagul, Xu Guancheng, Li Jinyu
College of Life Sciences, Xinjiang Normal University, Urumqi 830054, China.
Institute of Applied Chemistry, College of Chemistry, Xinjiang University, Urumqi 830046, China.
ACS Med Chem Lett. 2021 Feb 26;12(3):467-476. doi: 10.1021/acsmedchemlett.0c00680. eCollection 2021 Mar 11.
A novel pyrazolone-based copper complex [CuL(phen)(CHOH)][CuL(phen)]·CHCHOH·CHOH (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)(CHOH)] and [CuL(phen)]:Cu1 center with six coordination mode and Cu2 center with five coordination mode. The growth of BEL-7404 cells and H22 cells was significantly inhibited by P-FAH-Cu-phen with IC values of 1.175 μg/mL and 1.097 μg/mL, respectively, which were much lower than IC 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.
合成并表征了一种新型的基于吡唑啉酮的铜配合物[CuL(phen)(CHOH)][CuL(phen)]·CHCHOH·CHOH（P-FAH-Cu-phen）。P-FAH-Cu-phen的不对称结构单元由两个独立的配合物单元[CuL(phen)(CHOH)]和[CuL(phen)]组成：具有六配位模式的Cu1中心和具有五配位模式的Cu2中心。P-FAH-Cu-phen对BEL-7404细胞和H22细胞的生长具有显著抑制作用，IC值分别为1.175μg/mL和1.097μg/mL，远低于顺铂对BEL-7404细胞（23.32μg/mL）和H22细胞（27.5μg/mL）的IC值。P-FAH-Cu-phen通过线粒体和内质网应激相关途径诱导BEL-7404细胞的细胞周期阻滞于G2/M期并引发凋亡。此外，P-FAH-Cu-phen在H22肿瘤小鼠模型中显著抑制BEL-7404细胞的迁移和肿瘤生长，且无严重副作用，并提高了肿瘤小鼠的存活率。结果表明，P-FAH-Cu-phen可能是一种治疗肝癌的潜在候选药物。
