Study On The Anticancer Activity And Biological Macromalecules Interactions Of The Substituted Terpyridine Palladium And Zinc Complexes

In recent years,pyridyl-based metal complexes have been extensively studied in the medical imaging and disease therapeutic applications.The terpyridine complexes have received more and more attention in many fields,especially in cancer treatment,because of its excellent planarity and optical properties,as well as the fact that the terpyridine structure can induce property changes easily by introducing functional groups.In this thesis,19 palladium or zinc complexes with phenyl-terpyridine ligands based on different substituent groups at phenyl were designed and synthesized.Their structures were characterized by H¹ NMR,X-ray single crystal diffraction,FT-IR and elemental analysis.Their anticancer activities and binding properties with biological macromolecules were systematically studied.The specific research works of this thesis are as follows:1.Three zinc terpyridine complexes were prepared using4′-（p-hydroxy-phenyl）-2,2′:6′,2′′-terpyridine（L¹）,4′-（o-hydroxy-phenyl）-2,2′:6′,2′′-terpyridine（L²）and 4′-（m-hydroxy-phenyl）-2,2′:6′,2′′-terpyridine（L³）reacting with zinc formate.Their solid fluorescent properties were measured and compared.The antiproliferative activities of these complexes were evaluated by cell experiment with human lung cancer cells（A549）,human cancer cells（Bel-7042）and human breast cancer cells（MCF-7）in vitro.The measurement of UV-vis spectroscopy,circular dichroism（CD）and molecular docking simulation were carried out to study the binding ability and binding sites of the three complexes with DNA and protein,and the results were analyzed.2.Six new zinc（Ⅱ）complexes were synthesized by the reaction of zinc bromide or zinc iodide with 4’-（substituted-phenyl）-2,2’:6’,2’’-terpyridine and characterized by the same method.The solid fluorescent properties of the complexes at room temperature and their solution stability under physiological conditions were determined.The antiproliferative activities of these zinc（Ⅱ）complexes were monitored by cell experiment with Eca-109（human esophageal cancer cells）,A549 and Bel-7042 in vitro,and their cytotoxicity was evaluated by mononuclear macrophage cell line RAW264.7.The interactions of these complexes with CT-DNA and bovine serum albumin（BSA）were studied by UV-Vis spectroscopy,CD,fluorescent spectroscopy and molecular docking,respectively,and these results were analyzed.3.Ten Pd（Ⅱ）complexes were obtained by the reaction of palladium chloride with 4’-（substituted-phenyl）-2,2’:6’,2’’-terpyridine and characterized.Two structures were determined.The antiproliferation experiment of the complexes against four cancer cell lines MCF-7,A549,Bel-7402 and Eca-109and cytotoxicity experiment of four normal cell lines(Mouse embryonic fibroblasts（3T3）,hamster kidney cells（BHL-21）,human lung fibroblast（HLF）and human normal hepatocytes（HL-7702）in vitro were carried out.Simultaneously,molecular docking simulation calculations were simulated between Pd（Ⅱ）complexes and biological macromolecules（including B-DNA,oligonucleotide ds（ATGCAT）₂ or DNA-TopoⅠ）using molecular docking software,and the calculation results were analyzed.In the antiproliferation experiments,all the complexes exhibited better antitumor activity than the cisplatin,and their activity is related to the type and position of substituents.The IC₅₀ of normal cells compared with those of cancer cells showed a degree of selectivity.Different methods were used to study the binding of the complex to DNA or BSA,and the results prove that the complexes can effectively bind to DNA or BSA.