Synthesis, Structures And Antitumor Activities Of Polynuclear Complexes Based On DNA Interactions | | Posted on:2010-01-12 | Degree:Doctor | Type:Dissertation | | Country:China | Candidate:W Sun | Full Text:PDF | | GTID:1101360275981276 | Subject:Medicinal chemistry | | Abstract/Summary: |  PDF Full Text Request | | This dissertation aims at finding anticancer and antibacterial polynuclear complexes targeting DNA with high activity and low toxicity. Sixteen compounds were synthesized, and characterized by means of X-ray single crystal diffraction, elemental analysis, molar conductivity and IR, and the influencing factors on structures of the compounds have been investigated. The actions of these compounds to DNA were also investigated by spectral, electrochemical and hydromechanical methods. Finally, the cytotoxic and antibacterial activities of the oxamido-bridged binuclear complexes were studied in vitro.. This dissertation consists of three sections as follows:1. The crystal structure of a oxamide dinitrate, (1) [H4dmaeoxd](NO3)2 [H2dmaeoxd = N,N'-bis[2-(dimethylamino)ethyl]oxamide], has been obtained. The diversity of complexes with different structures is carried out by successful synthetic strategy of controlling species of metal ions, counter anions, pH values and solvents in the course of synthesis. Four dinuclear complexes bridged by trans-dmaeoxd2-: [Cu2(dmaeoxd)(bpy)2](ClO4)2 (2), [Cu2(dmaeoxd)(phen)2](ClO4)2 (3),,[Cu2(dmaeoxd)(Me2phen)2](ClO4)2 (4), [Cu2(dmaeoxd)(SCN)2(H2O)2] (5); Four dinuclear complexes bridged by cis-dmaeoxd2-: [Ni(dmaeoxd)Ni(dmbp)2](ClO4)2 (6), [Cu(dmaeoxd)Ni(bpy)2](ClO4)2·2CH3OH (7), [Cu(dmaeoxd)Zn(bpy)2]- (ClO4)2·2H2O (8), [Cu(dmaeoxd)(H2O)Ni(phen)2](ClO4)2.0.5CH3OH (9); three 1-D polynuclear complexes: [Cu2(dmaeoxd)(ox)]n·nH2O (10), [Cu2(H2O)2(dmaeoxd)- (bdc)]n·4nH2O (11), [Cu2(dmaeob)(H2O)(phen)]n(NO3)n·2nH2O (12); one 2-D polynuclear complex,[Cu6(oxen)3(μ3-OH)2(H2O)2]n(ClO4)4n.2nH2O (13); the others: [VO(ox)(bpy)(H2O)]·2H2O (14), [Zn2(ox)(bpy)4](ClO4)2·H2O (15), [Cu(Miloxicamin)2]·2DCM (16) have been synthesized and characterized by X-ray single crystal diffraction, elemental analysis, IR spectra. The coordination mode and supermolecular structure of the compounds were also studied. 2. DNA binding studies of the compounds with HS-DNA have been studied by the spectroscopic (absorption and emission spectra), electrochemical and hydromechanical measurements. The results show that the interaction mode of most complexes is intercalation, except for complex (5) and complex (11). The effects of metal ions, terminal ligands and cis/trans conformation of oxamide on DNA interactions were also studied.3. The cytotoxic and antibacterial activities of the oxamido-bridged binuclear complexes (trans-homo-, cis-homo- and cis-heterobinuclear) were studied in vitro. 1). The antibacterial activities of the complexes were tested by the paper disc method and the microdilution broth method, and all the complexes display antibacterial activities. 2). The cytotoxicities of the complexes were tested by MTT and SRB methods. The results show that most of the complexes have the cytotoxic activities. Complexes (3) and (4) with the strongest DNA binding activities have the strongest effects on SMMC-7721 and A549 cell lines, with the IC50 = 2030 ng/mL.These researches not only enriched the content of inorganic medicinal chemistry, but also supplied valuable information for design and synthesis of inorganic chemotherapeutic medicine with high activity and low toxicity.
| | Keywords/Search Tags: | Oxamide ligand, Polynuclear complexes, Crystal structure, DNA interaction, Cytotoxicity, Antibacterial activity | | PDF Full Text Request | Related items |
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