Synthesis, Structures And Anticancer Activity Of N,N’-disubstituted Oxamides-bridged Binuclear Copper(Ⅱ) Complexes Based On DNA-binding Properties

Copper, one of14kinds of essential trace elements for human, acts an important role inconstituting human body and regulating physical function. In drug design and syhthesis, theeffective utilization of copper has a positive impact on the development of new drugs and theimprovement of drug effect. Affected by the application of cisplatin, carboplatin and other platinumcompounds in anticancer field, metal drugs, especially those targeting at the DNA molecules incancer cells, have become the focus of anticancer drug design, but so far, there are few drugs hasentered clinical trials. In order to find anticancer drugs with low toxicity and high efficiency, thisthesis has used copper as the central atom of metal complexes, chosen two N,N’-disubstitutedoxamides as the ligands, synthesised a series of oximide-bridged polynuclear copper（Ⅱ） complexes,and obtained five monocrystals; at the same time, the DNA-binding properties and citotoxities ofthe monocrystals have been studied systematically. The detailed contents are as followed:1. Synthesis and structures of polynuclear complexes: five complexes were synthesized andcharacterized by choosing N-（2-hydroxyphenyl）-N’-（3-aminopropyl）oxamide （H₃papo） andN-（5-chloro-2-hydroxyphenyl）-N’-[3-（methylamino）propyl]oxalamide （H₃chmpoxd） as the bridgingligands, including[Cu₂（papo）（phen）（H₂O）]（ClO₄）·2H₂O （1）,[Cu₂（papo）（Me₂bpy）（CH₃CH₂OH）]（pic）（2）,[Cu₂（chmpoxd）（H₂O）（bpy）]ClO₄·H₂O（3）,[Cu₂（chmpoxd）（H₂O）（bpy）]Cl·3H₂O （4）,[Cu₂（chm-poxd）（H₂O）（bpy）]NO₃·CH₃CN （5）. Their structures have been characterized by elemental analyses,IR and single-crystal X-ray diffraction.2. Interactions of complexes with DNA: the DNA-binding properties of the complexes havebeen studied by the electronic and fluorescence spectra, electrochemical measurements andviscosity measurements. Besides, the impacts of terminal ligands and counter-ions on theinteractions between complexes with HS-DNA were also investigated.3. In vitro citotoxities activities of complexes: The in vitro citotoxities of complexes （1）-（5）against two cancer cell lines: human hepatocellular carcinoma cell line SMMC-7721and humanlung adenocarcinoma cell line A549were tested by SRB method, the results indicate that all of thecomplexes have a certain cytotoxicities against SMMC-7721and A549cell lines.The researches of this dissertation enrich the content of oxamide-bridged polynuclearcomplexes, supply the chemical basis to explore novel bridging polynuclear complexes with highactivity, low toxicity and antitumor activities, and could be the valuable references for studying therelationship between structures and properties of complexes.