School of Chemical Science and Technology, Yunnan University, Kunming 650091, Yunnan, China.
Department of Chemical Biology and Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin 300070, China.
J Inorg Biochem. 2020 Jul;208:111103. doi: 10.1016/j.jinorgbio.2020.111103. Epub 2020 May 19.
A new Schiff base copper(II) complex [N,N'-bis(2'-hydroxyphenylacetone)-o-ethanediamine] copper (II) (M1) has been synthesized and characterized by single X-ray crystallography. The cytotoxicity of complex M1 was evaluated against HeLa, LoVo, A549, A549/cis cancer cell lines, and the normal cell lines LO2 and HUVEC, by MTT (3-(4,5-dimethylthiazoyl-2-yl)2,5-diphenyltetrazoliumbromide) assays. The IC (50% inhibition concentrations) is in the range of 5.13-11.68 μM, which is somewhat lower than cisplatin on the basis of platinum molar concentration. Furthermore, anticancer mechanistic studies showed that the complex M1 inhibited cell proliferation by blocking DNA synthesis and then acted on nuclear division of HeLa cells over time. Moreover, M1 increased intracellular ROS (Reactive oxygen species) levels in a dose-dependent manner. Western blot analysis indicated M1 dramatically decrease c-Myc transcription factor and KLF5 (Krüppel-like factor 5) protein expression levels in HeLa. M1 did not inhibit proteasomal activity. Finally, M1 induced DNA damages and activated the DNA damage repair pathways.
一种新的希夫碱铜（II）配合物[N，N'-双（2'-羟基苯乙酮）-o-乙二胺]铜（II）（M1）已通过单晶 X 射线衍射法合成并进行了表征。通过 MTT（3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四唑溴化物）测定法评估了配合物 M1 对 HeLa、LoVo、A549、A549/cis 癌细胞系和正常细胞系 LO2 和 HUVEC 的细胞毒性。IC（50%抑制浓度）在 5.13-11.68 μM 范围内，基于铂摩尔浓度，其略低于顺铂。此外，抗癌机制研究表明，该配合物 M1 通过阻断 DNA 合成并随时间作用于 HeLa 细胞的核分裂来抑制细胞增殖。此外，M1 以剂量依赖性方式增加细胞内 ROS（活性氧）水平。Western blot 分析表明，M1 显著降低了 HeLa 中的 c-Myc 转录因子和 KLF5（Krüppel 样因子 5）蛋白表达水平。M1 不会抑制蛋白酶体活性。最后，M1 诱导 DNA 损伤并激活 DNA 损伤修复途径。
