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Structure And Biological Activity Of Copper-aromatic Polya Cid-pyridine (Imidazole) Complexes

Posted on:2020-05-20Degree:MasterType:Thesis
Country:ChinaCandidate:J X LiuFull Text:PDF
GTID:2381330590497416Subject:Chemical Engineering and Technology
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As we all know,tumors are one of the world's problems.The current methods for treating malignant tumors?cancers?mainly include radiation therapy,surgery and chemotherapy.More and more cancer patients choose chemotherapy under the comprehensive consideration of various factors.Platinum anticancer agents are indispensable drugs in clinical chemotherapy.Among them,the application of three platinum-containing drugs such as cisplatin,carboplatin and oxaliplatin in human cancer treatment has been recognized by researchers all over the world.However,platinum anticancer agents also have certain limitations,such as low solubility,nephrotoxicity and drug resistance,which limit the clinical application of platinum drugs to some extent.Therefore,the search for more effective,low toxic side effects of metal complexes has become the focus of research in the field of anticancer drugs.In recent years,metal complexes have attracted the attention of researchers in the fields of chemistry and pharmacy due to their structural diversity and potential pharmaceutical value.Designing and synthesizing metal complexes with novel structure and excellent performance from heterocyclic aromatic nitrogen base ligands has become a hot spot in coordination chemistry and inorganic medicinal chemistry.The heterocyclic aromatic nitrogen base ligands are rich in coordination sites and special properties of the resonance structure,and exhibit good biological activity after formation of the metal complex.Therefore,the study of the structure and properties of heterocyclic aromatic nitrogen base metal complexes is of great significance for the development of anticancer drugs.Inthiscontext,L1=2,5-bis?3,5-carboxyphenyl?terephthalicacidand L2=2,5-bis?3-carboxyphenyl?terephthalic acid are the main ligands.Complex 1 and 2 are synthesized by hydrothermal method using L3=3,5-bis?1-imidazolyl?pyridine as a secondary ligand,[Cu?L1?2?L3?2]n?1?,[Cu?L2?2?L3?3]n?2?.1.The crystal structures of the three complexes were determined by single crystal X-ray crystal ography.2.Fluorescence and UV spectra show the binding ability of complex 1 and 2 to fish sperm DNA?FS-DNA?,revealing the interaction mode of complex with FS-DNA;3.Agarose gel electrophoresis assay showed the ability of the metal complex to cleave pBR322 plasmid DNA;4.Molecular docking results indicate that both complexes 1 and 2 are capable of interacting with DNA with special functions,that the double helix DNA is unwinded and embedded in the base pair;5.The ability of complexes 1 and 2 to induce apoptosis of HeLa cells was determined by flow cytometry,and color photographs were obtained by fluorescence inverted microscope.These images clearly showed morphological changes in metal complexes against human cervical cancer HeLa cel s.The results showed that both complex 1 and DNA could intercalate with DNA,which could affect the stability of further DNA and have a good induction of apoptosis in HeLa cells,which provided a new direction for the development of anticancer drug materials.The results showed that the complex 1 and 2 could interact with DNA,thereby affecting the stability of DNA and inducing apoptosis of HeLa cells.It can be used as an anticancer drug for future development.
Keywords/Search Tags:Complexes, Anti-cancer, DNA interaction, Molecular docking
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