Qi Jinxu, Liu Taichen, Zhao Wei, Zheng Xinhua, Wang Yihong
School of Chemistry and Chemical Engineering, Southeast University Nanjing 211189 China.
School of Medicine, Pingdingshan University Pingdingshan China.
RSC Adv. 2020 May 18;10(32):18553-18559. doi: 10.1039/d0ra02913k. eCollection 2020 May 14.
We have prepared six thiosemicarbazone ligands and synthesized the corresponding Ga(iii) complexes. The antitumor activity of the ligand increases with its lipophilicity, and the antitumor activity of the Ga(iii) complexes is affected by the ligands. Since C6 has the highest anticancer proliferative activity (0.14 ± 0.01 μM) against HepG-2 (Human hepatocarcinoma cell line), we characterized its structure by X-ray single crystal diffraction and explored its antiproliferation mechanism. Anti-tumor mechanism results show that Ga(iii) complex (C6) promoted HepG-2 cell cycle arrest in the G1 phase by regulating the expression of cell cycle-associated proteins (Cdk 2, cyclin A and cyclin E). Ga(iii) complex (C6) promotes apoptosis by consuming intracellular iron, enhancing intracellular reactive oxygen species (ROS), activating caspase-3/9, releasing cytochromes and apoptotic protease activating factor-1 (apaf-1).
我们制备了六种硫代氨基脲配体，并合成了相应的Ga(III)配合物。配体的抗肿瘤活性随其亲脂性增加而增强，且Ga(III)配合物的抗肿瘤活性受配体影响。由于C6对HepG-2（人肝癌细胞系）具有最高的抗癌增殖活性（0.14±0.01μM），我们通过X射线单晶衍射对其结构进行了表征，并探究了其抗增殖机制。抗肿瘤机制结果表明，Ga(III)配合物（C6）通过调节细胞周期相关蛋白（Cdk 2、细胞周期蛋白A和细胞周期蛋白E）的表达，促进HepG-2细胞周期停滞于G1期。Ga(III)配合物（C6）通过消耗细胞内铁、增强细胞内活性氧（ROS）、激活半胱天冬酶-3/9、释放细胞色素和凋亡蛋白酶激活因子-1（apaf-1）来促进细胞凋亡。
