Studies On The Synthesis, Characterization And Bioactivities Of The Glutathione Schiff Base Complexes

Glutathione is one small molecules containing sulphur three peptide thatcondensated by glutamic acid, cysteine and glycine, belongs to a kind of amino acidderivatives, it participates in a variety of important biological chemical processes inplants and animals. Transition metal complexes with glutathione have certainbiological activity, its research is widely used in molecular biology, pharmaceuticalchemistry, clinical medicine and other fields. The amino of glutathione molecules andcarbonyl compounds can be formed Schiff bases, such Schiff Base has more activesite than the other amino acid Schiff Bases, and the peptide bond plays an importantrole in the organism. So the synthesis of new type of small molecular peptide SchiffBase and metal complexes, molecular structure and biological activity is greatsignificance of new drug development.In this paper, we choose three carbonyl compounds that have different structuresreacting with glutathione and we get three Schiff Base solution. Then the Schiff Basereact with different transition metal ions and we get more than twenty Schiff Basecomplexes that have not been reported. The structure were characterized andestimated by elemental analysis, infrared spectroscopy, ultraviolet-visiblespectroscopy, nuclear magnetic analysis, TG-DTG analysis and other methods.Fluorescence spectrum analysis of part complexes are tested. The mode of interactionof between part complexes with CT-DNA is studied. The inhibiting proteasome andinducing apoptosis of part complexes on breast cancer cells are studied by targetingthe cellular proteasome. The main works as follows:(1) Five kinds of metal complexes derived from glutathione and o-vanillinwere synthetized. The complexes were characterized by elemental analysis,IR spectroscopy,1H NMR, and other characterization methods, and we speculate the compositions of the complexes as follows: Cu2[(C18H23N3O8S)(H2O)2(CH3O)], Cd2[(C18H23N3O8S)(H2O)2(CH3O)]·2H2O, Mn2[(C18H23N3O8S)(H2O)2(CH3O)]·2H2O, Zn2(C18H23N3O8S)(H2O)2(CH3O)]·2H2O, Ni2[(C18H23N3O8S)(H2O)2(CH3O)]. Fluorescence spectrum analysis of part complexes are tested, and we found that complex Cu2[(C18H23N3O8S)(H2O)2(CH3O)] has good fluorescence activity.(2) Five kinds of metal complexes derived from glutathione and2-hydroxy-1-naphthalene formaldehyde were synthetized. The complexes were characterized by elemental analysis, IR spectroscopy and other characterization methods, and we speculate the compositions of the complexes as follows: Cu2[(C21H21N3O7S)(H2O)2(CH3O)2], Zn2[(C21H21N3O7S)(H2O)2(CH3O)2], Cr2[(C21H21N3O7S)(H2O)2(CH3O)2], Co2[(C21H21N3O7S)(H2O)2(CH3O)2], Ni2[(C21H21N3O7S)(H2O)2(CH3O)2].Fluorescence spectrum analysis of part complexes are tested, and we found that complex Cu2[(C21H21N3O7S)(H2O)2(CH3O)2] has good fluorescence activity.(3) Five kinds of metal complexes derived from glutathione and vanillin were synthetized. The complexes were characterized by elemental analysis, IR spectroscopy and other characterization methods, and we speculate the compositions of the complexes as follows: Cu2[(C18H20N3O8S)(H2O)2(CH3O)2], Zn2[(C18H20N3O8S)(H2O)2(CH3O)2], Ni2[(C18H20N3O8S)(H2O)2(CH3O)2], Cd2[(C18H20N3O8S)(H2O)2(CH3O)2], Co2[(C18H20N3O8S)(H2O)2(CH3O)2]. Fluorescence spectrum analysisof part complexes are tested, and we found that complex Cd2[(C18H20N3O8S)(H2O)2(CH3O)2] has good fluorescence activity.(4) Six kinds of metal complexes derived from glutathione and o-vanillin-1,10-phenanthroline were synthetized. The complexes were characterized by elemental analysis,IR spectroscopy,1H NMR, and other characterization methods, andwe speculate the compositions of the complexes as follows: Cu2(C18H23N3O8S)(C12H8N2)2,Cr2(C18H23N3O8S)(C12H8N2)2,Ni2(C18H23N3O8S)(C12H8N2)2,Zn2(C18H23N3O8S)(C12H8N2)2,Co2(C18H23N3O8S)(C12H8N2)2,Mn2(C18H23N3O8S)(C12H8N2)2.(5) The interaction of the [(C18H23N3O8S)(H2O)2(CH3O)] with CT-DNA hasbeen investigated by UV-Vis spectrometry, viscosity experiment, and EB-DNAexperiment. The results show that the interaction of complex and DNA isintercalation. (6) In the thesis, the antitumor activity of part complexes is screened throughMTT method, then the complexes Cu2[(C18H23N3O8S)(H2O)2(CH3O)] andCu2(C18H23N3O8S)(C12H8N2)2that have good inhibitory to MDA MB231breastcancer cell is screened. Choose ternary complex that has better inhibitory and study itsantitumor mechanism of further research, explore its effect of chymotrypsin inhibitionand apoptosis induction. The results show that the ternary complex could inhibitprotease activity and induce tumor cell apoptosis of MDA MB231breast cancer cell,and concentration of the complex and action time are positively correlated to theeffect of inhibitory. Ternary copper complex of antitumor activity is better than theSchiff Base complex, it may be related to the second ligand1,10-phenanthroline tochange its structure.