Tryptanthrin derivatives copper(II) complexes with high antitumor activity by inhibiting telomerase activity, and inducing mitochondria-mediated apoptosis and S-phase arrest in BEL-7402
Tryptanthrin derivatives copper(II) complexes with high antitumor activity by inhibiting telomerase activity, and inducing mitochondria-mediated apoptosis and S-phase arrest in BEL-7402
复制标题
色胺酮衍生物铜 (ii) 复合物通过抑制端粒酶活性并诱导 BEL-7402 中线粒体介导的细胞凋亡和 S 期阻滞而具有高抗肿瘤活性
DOI：
10.1039/c8nj03005g
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发表时间：
2018
影响因子：
3.3
通讯作者：
Hong Liang
中科院分区：
文献类型：
--
作者：
Qi-Pin Qin;Bi-Qun Zou;Ming-Xiong Tan;Shu-Long Wang;Yan-Cheng Liu;Hong Liang
合成了色氰菊酯(Try)和8-溴色氰菊酯(BrTry)的铜(II)配合物[CuII(Try)2Cl2](Try-Cu)和[CuII(BrTry)2Cl2](BrTry-Cu)，并用光谱分析和单晶X-射线衍射法对其进行了表征。Try-Cu和BrTry-Cu络合物中的铜(II)中心采用近似六配位的扭曲八面体几何构型。分别对四种人肝癌细胞系(BEL-7402、T-24、MGC80-3和HepG2细胞)和一种正常人肝细胞系(HL-7702细胞)进行了体外抗癌活性研究。结果表明，Try-Cu对四种肿瘤细胞具有选择性细胞毒作用(IC_(50)=4.02~9.03μM)，而对正常人肝HL-7702细胞的细胞毒作用较弱。进一步的研究表明，Try-Cu主要通过诱导DNA损伤，使细胞周期停滞在S期，以及通过与c-myc启动子相互作用，刺激线粒体功能障碍和抑制端粒酶而发挥其细胞毒作用。
The copper(II) complexes of tryptanthrin (Try) and 8-bromo-tryptanthrin (BrTry), [CuII(Try)2Cl2] (Try-Cu) and [CuII(BrTry)2Cl2] (BrTry-Cu), were synthesized and fully characterized by spectroscopic methods and single-crystal X-ray diffraction analysis. The copper(II) centers in the Try-Cu and BrTry-Cu complexes adopted an approximately six-coordinated distorted octahedral geometry. The anticancer activities of Try-Cu and BrTry-Cu were evaluated in vitro against four human cancer cell lines (BEL-7402, T-24, MGC80-3, and HepG2 cells) and one normal human liver cell line (HL-7702 cells). It was found that Try-Cu exhibited selective cytotoxicity against the four selected cancer cells (IC50 = 4.02–9.03 μM) but low cytotoxicity toward the normal human liver HL-7702 cells. Further studies revealed that Try-Cu exhibited its cytotoxic activity mainly by inducing DNA damage and thus causing cell cycle arrest in the S phase, as well as stimulating mitochondrial dysfunction and inhibiting telomerase by interacting with the c-myc promoter.