Synthesis, Interaction With DNA/BSA Of Metal Complexes With Demethylcantharate And Benzimidazole (Thiazole)

The number of metal compounds in current clinical use for the treatment of cancer is extremely limited and concerns platinum compounds exclusively. The use of Pt anticancer drugs is restricted by severe toxicity and by spontaneous or acquired resistance. With the aim of overcoming these limits, a huge number of other metal compounds were extensively investigated over the years; an increasing number of metal compounds have shown interesting biological and bio-medical properties (e.g. antiproliferative activity against cancer cells, inhibition of enzymes). Demethylcantharate is the derivatives of anticancer drug of cantharidin, has strong antitumor activity and low cytotoxicity. So we have designed and synthesized three kinds of novel metal complexes with demethylcantharate and heteroaromatic compound:The interactions of these complexes with DNA and bovine serum albumin (BSA) have taken place, and the interaction strength was measured and the interactive mode was obtained. Meanwhile, preliminary discussions of the structure-activity relationship between the interactions of the complexes with biological macromolecules have taken place.The main work is as following:Twelve novel complexes (Hambi)[Ln(DCA)2(H2O)3]·3H2O (Ln(Ⅲ)=La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm; DCA=7-oxabicyclo [2.2.1]heptane-2,3-dicarboxylate, demethylcantharate, C8H8O5; Hambi=protonated2-aminomethylbenzimidazole, C8H10N3) were synthesised and characterized by elemental analysis, infrared spectra and thermogravimetric analysis. The complexes structure of Pr (1) and Sm (2) were determined by X-ray diffraction, the complex Pr(1) and Sm (2) crystallized in the monoclinic crystal system with P2(1)/c space group. Binding properties of complexes with DNA were investigated by mean of spectroscopic method (electronic absorption spectra and fluorescence spectra) and viscosity measurements. The interaction of complexes with bovine serum albumin (BSA) was studied by fluorescence spectra. The antiproliferative activities of the complex Pr and Sm against human hepatoma cells (SMMC7721) were tested with MTT assay in vitro. The antiproliferative activities of the complexes against the cells was more intense than Na2(DCA).Eleven novel rare earth complexes (Habtz)[Ln(DCA)2(H2O)2]·2H2O (Ln(Ⅲ)=La, Ce, Pr, Nd, Sm, Gd, Tb, Dy, Ho, Er, Tm; DCA=demethylcantharate, C8H8Os; Habtz=protonated2-aminobenzothiazole, C7H7N2S) were synthesized and characterized by elemental analysis, infrared spectra and thermogravimetric analysis. The binding properties of the complexes with DNA were investigated by viscosity measurements and spectroscopic method (electronic absorption spectra and fluorescence spectra). The interaction of complexes with bovine serum albumin (BSA) was studied by fluorescence spectra. All the results indicated that two kinds of complexes above-mentioned bind to DNA in the mode of partial intercalation moderately. The fluorescence of BSA was quenched by the complexes through a static process.Two novel complexes [Mn2(ambi)2(DCA)2]·8H2O (3),[Cd2(ambi)2(DCA)2]·4H2O (4)(ambi=2-aminomethylbenzimidazole, C8H9N3) were synthesized and characterized by elemental analysis, molar conductance, infrared spectra, thermogravimetric analysis and X-ray diffraction. Mn (3) complex and Cd (4) complex crystallized in monoclinic crystal system with P2(1)/n space group and triclinic crystal system with P-1space group, respectively. Binding properties of the complexes with DNA were investigated by spectroscopic method (electronic absorption spectra and fluorescence spectra) and viscosity measurements. The interaction of complexes with bovine serum albumin (BSA) was studied by fluorescence spectra. All the results indicated that the complexes bind to DNA in the mode of partial intercalation moderately. The fluorescence of BSA was quenched by the complexes through a static process.