Shi Pengfei, Jiang Qin, Zhao Yongmei, Zhang Yangmiao, Lin Jun, Lin Liping, Ding Jian, Guo Zijian
State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, People's Republic of China.
J Biol Inorg Chem. 2006 Sep;11(6):745-52. doi: 10.1007/s00775-006-0120-y. Epub 2006 Jun 9.
Four gold(III) complexes of terpyridine derivatives 1-4 have been synthesized and characterized by spectroscopic methods. In vitro data demonstrated that all of them showed higher cytotoxicity than cisplatin against the human non-small-cell lung cancer cell line (A-549), the human stomach carcinoma cell line (SGC-7901), the human cervix carcinoma cell line (HELA), the human colon carcinoma cell line (HCT-116), the human liver carcinoma cell line (BEL-7402), the murine leukemia cell line (P-388) and the human acute promyelocytic leukemia cell line (HL-60). Complex 3 exhibits the highest activity, with growth inhibition rates of over 80% at 10(-8) mol L(-1) against the A-549, HCT-116 and HELA tumor cell lines. Interestingly, ligands L1-L4 are also very cytotoxic against the cell lines tested. Complexes 1-4 are stable in aqueous solution for 2 days in the presence of the biological reducing agent glutathione. The inductively coupled plasma mass spectrometry data showed that DNA isolated from cells treated with complexes 1 and 3 contained gold with gold-to-nucleotide ratios of approximately 1:6,400 and 1:4,900, respectively. Fluorescence titration, UV and circular dichroism analyses proved that the steric and electrostatic effects of the ligand remarkably influence the interactions of their gold(III) complexes with DNA. The DNA binding ability of the complexes has been correlated with their cytotoxicity, which could potentially provide a new rationale for the future design of terpyridine-based metal complexes with antitumor potential.
合成了四种三联吡啶衍生物1 - 4的金（III）配合物，并通过光谱方法对其进行了表征。体外数据表明，它们对人非小细胞肺癌细胞系（A - 549）、人胃癌细胞系（SGC - 7901）、人宫颈癌细胞系（HELA）、人结肠癌细胞系（HCT - 116）、人肝癌细胞系（BEL - 7402）、小鼠白血病细胞系（P - 388）和人急性早幼粒细胞白血病细胞系（HL - 60）均显示出比顺铂更高的细胞毒性。配合物3表现出最高的活性，在10⁻⁸ mol L⁻¹浓度下对A - 549、HCT - 116和HELA肿瘤细胞系的生长抑制率超过80%。有趣的是，配体L1 - L4对所测试的细胞系也具有很强的细胞毒性。在生物还原剂谷胱甘肽存在下，配合物1 - 4在水溶液中稳定2天。电感耦合等离子体质谱数据表明，用配合物1和3处理的细胞中分离出的DNA含有金，金与核苷酸的比例分别约为1:6400和1:4900。荧光滴定、紫外和圆二色性分析证明，配体的空间和静电效应显著影响其金（III）配合物与DNA的相互作用。配合物的DNA结合能力与其细胞毒性相关，这可能为未来设计具有抗肿瘤潜力的基于三联吡啶的金属配合物提供新的理论依据。
