Study On Design, Synthesis And Bioactivities Of Multi-pyridine Ligands With Large Plane And Their Metal Complexes

Objective:To design and synthesize multi-pyridine ligand with large plane structure and corresponding metal complexes, using the synergistic action of metal ions with ligands, do screening for the discovery of new anticancer drugs and photosensitizers.Methods:First, adopt1,10-phenanthroline as the raw material, synthesize DPCL and DPCO through two-step chemical reaction, and further synthesize metal complexes of DPCL and DPCO. By infrared spectroscopy, mass spectrometry, X-ray diffraction and other methods, we determine the structures of ligands and their complexes. DNA binding ability with complexes are determined by fluorescence spectroscopy. and the interaction mechanism of complexes with DNA are studied by UV absorption spectra The interaction between complexes and pBR322DNA has also been investigated by gel electrophoresis. Solution of DPCLCu and DPCOCu was prepared. Inhibitor activity on clinical common tumor cell HGC7901, A549, MCF7were measured by MTT method, by which the inhibition rate was determined, and the activity differences between ligand and their complexes were also been compared. In addition, Ag complex of TMPA ((N-(pyridin-2-yl)-N-(pyridin-2-ylmethyl) pyridin-2-amine) was synthesized and determined by X-ray crystal diffraction.Result:DPCL, DPCO and their copper complexes have been synthesized. The chemical structures and physicochemical properties were also determined. Fluorescence spectra showed that the complexes have strong DNA binding ability. The hypochromisms and red-shifts observed in UV absorption spectra may suggest an intercalative mode. Agarose gel electrophoresis experiment shows that DNA cleavage activity of complexes are very well. Singlet oxygen and metal ions were main factor that caused DNA cleavage. MTT method showed that the ligand possess weak inhibitory activity on the tumor cells HGC7901, A549, MCF7, except DPCO has good inhibitory activity to A549. The complexes DPCLCu and DPCOCu have good inhibitory activity, and DPCOCu’s inhibition rate is a little better than DPCLCu.Conclusion:The interaction of complexes with CT-DNA were studied by fluorescence spectroscopy. Flurescence spectroscopy showed that:after joining the complex, EB-DNA fluorescence intensity decreases, and as the complex concentration increase the fluorescence intensity gradually decreased. It indicates that complex insert CT-DNA competitively and replace EB. Agarose gel electrophoresis experiments show that:it caused nuclease action under the conditions of oxidant and reductant, pBR322DNA can be converted from Form I into Form II, and with the increasing of complex concentration, DNA sequence increases the degree of fracture. The way of DNA cleavaged by complexes is the oxidation cleavage. Singlet oxygen and metal ions are the main mode of action. MTT method shows that compounds DPCL and DPCO have almost no inhibitory activity against cancer cells, while their complexes DPCLCu and DPCOCu are obvious biological activity. DPCOCu is a little better than DPCLCu. Such multi-pyridine compounds with anticancer activity are wealthy of further researching and development. The structure of the compounds can be further modified.