Font Size: a A A

Syntheses, DNA/BSA-binding And Cytotoxicities Studies Of Polynuclear Complexes With N-(2-hydroxyphenyl)- N’-[3-(Diethylamino)Propyl]Oxamide

Posted on:2016-02-18Degree:MasterType:Thesis
Country:ChinaCandidate:L TaoFull Text:PDF
GTID:2271330473958645Subject:Pharmaceutical engineering
Abstract/Summary:PDF Full Text Request
At present, exploring new effective anticancer drugs is an important topic owing to the shortage of metal anticancer drugs. As a very classical anticancer drug in the current used drugs, cis-platin can bind to DNA in covalent interaction which could inhibit the replication and transcription of DNA. The significant side-effects and the tolerance of cis-platin limit its clinical application. In order to find highly effective, target-specific and less toxic drugs, much effort has been devoted to the development of metal-based anticancer agents binding to DNA through non-covalent interaction.In this paper, we chose N-(2-hydroxyphenyl)-N’-[3-(diethylamino)propyl]-oxamide (H3hdpox) (1) as bridging ligand to design and syntheses a series of polynuclear metal complexes with different terminal ligands. Their structures have been characterized by single-crystal X-ray diffraction, IR spectra and elemental analysis. Furthermore, the DNA and bovine serum albumin(BSA) binding ability has been monitored by using UV absorption and fluorescence spectrum experiment, and the cytotoxic activity was determined in vitro. The detail contents mainly include the following three parts:1. Syntheses and structures of free ligand and polynuclear complexes:Five complexes were synthesized by choosing H3hdpox (1)as the bridging ligand, namely [Cu2(hdpox)(phen)(C2H5OH)](ClO4)·CH3CN (2), [Cu2(hdpox)(dabt)(CH3OH)] (ClO4)·0.5CH3OH (3), [Cu2(hdpox)(Me2bpy)(H2O)](ClO4) (4), [Cu3(hdpox)2-(H2O)]·H2O (5), [Ni3(hdpox)2]·H2O (6). Their structures have been characterized by X-ray single-crystal diffraction, IR spectra and elemental analysis.2. Interactions of compounds with DNA and BSA:To investigate the interaction of six compounds with DNA, UV absorption and fluorescence spectra, viscosity measurements have been used. Furthermore, the BSA-binding ability with the six compounds have been monitored by using UV absorption and tryptophan fluorescence quenching experiment. The results of DNA-binding experiment showed that the six compounds interact with DNA in the mode of intercalation. The better planarity of the terminal ligands in the complexes is in favor of the interaction between the complexes and DNA, while the enlarged steric hindrance of the terminal ligands inhibits such interaction. The DNA-binding activity of trinickel(Ⅱ) complex is weaker than tricopper(Ⅱ) complex. The BSA binding experiment showed that the six compounds can all interact with BSA and their quenching mechanism for extincting BSA endogenous fluorescence is static quenching.3. In vitro citotoxities activities of compounds:We also tested in vitro cytotoxic activities of six compounds against human hepatocellular carcinoma line (SMMC-7721) and human lung adenocarcinoma cell line(A549) by SRB assays, and the results shows:six compounds cytotoxic activities following the order of 2> 3> 4 and 5> 6, which is consistent with their DNA-binding abilities. The results attest that DNA is the target of the metal complexes.
Keywords/Search Tags:Asymmetric oxamide, Polynuclear complexes, Crystal structure, DNA/BSA interaction, In vitro anticancer activities
PDF Full Text Request
Related items