Sutradhar Manas, Roy Barman Tannistha, Fernandes Alexandra R, Paradinha Fabiana, Roma-Rodrigues Catarina, Guedes da Silva M Fátima C, Pombeiro Armando J L
Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal.
Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal.
J Inorg Biochem. 2017 Oct;175:267-275. doi: 10.1016/j.jinorgbio.2017.07.034. Epub 2017 Aug 2.
A series of four mixed ligand aroylhydrazone and N-donor heterocyclic Lewis base Cu(II) complexes [CuL(X)] [L refers to the dianionic form of (5-bromo-2-hydroxybenzylidene)-2-hydroxybenzohydrazide; X=pyrazine (Pz; 1), pyridine (Py; 2), imidazole (Imz; 3) and 3-pyridinecarbonitrile (3-PyCN; 4)] has been synthesized and characterized by elemental analysis, various spectroscopic techniques and X-ray crystallography (for 1, 2 and 4). The antiproliferative effect of complexes 1-4 was examined in 4 human tumor cell lines (ovarian carcinoma (A2780), colorectal carcinoma (HCT116), lung adenocarcinoma (A549) and breast adenocarcinoma (MCF7)) and in normal human primary Fibroblasts. Complex 4 exhibits a high cytotoxic activity against ovarian and colorectal carcinoma cells (A2780, HCT116 respectively), with IC much lower than those for normal primary fibroblasts. Complex 4 could induce cell death via apoptosis but not autophagy in colorectal carcinoma cells.
合成了一系列由四种混合配体芳酰腙和含氮供体杂环路易斯碱构成的铜（II）配合物[CuL(X)] [L指(5-溴-2-羟基亚苄基)-2-羟基苯甲酰肼的二阴离子形式；X = 吡嗪（Pz；1）、吡啶（Py；2）、咪唑（Imz；3）和3-吡啶甲腈（3-PyCN；4）]，并通过元素分析、各种光谱技术和X射线晶体学（针对1、2和4）对其进行了表征。在4种人类肿瘤细胞系（卵巢癌（A2780）、结肠直肠癌（HCT116）、肺腺癌（A549）和乳腺腺癌（MCF7））以及正常人原代成纤维细胞中检测了配合物1 - 4的抗增殖作用。配合物4对卵巢癌和结肠直肠癌细胞（分别为A2780、HCT116）表现出高细胞毒性活性，其半数抑制浓度（IC）远低于正常原代成纤维细胞的IC。配合物4可通过诱导结肠直肠癌细胞凋亡而非自噬来导致细胞死亡。
