Synthesis, Crystal Structure And Interaction With DNA And Bsa Of Transition-Metal Complexes With Benzimidazole And Norcantharidin Imide

Cancer is a serious disease that is a threat to human safety. Currently, studying novel anticancer drugs is a hot spot in the field of biochemistry research. People find that a growing number of transition metal compounds show a wide range of biological activity. Demethylcantharate is the derivatives of traditional anticancer drug of cantharidin. It not only possesses intense antiproliferative activity in vitro, but also possesses less damage to normal cells. Therefore, we take demethylcantharate as a lead compound, not only designed and synthesized three types of N-nitrogen heterocyclic demethylcantharate imide, but also designed and synthesized novel demethylcantharate and benzimidazole derivatives transition-metal complexes. We also have studied the interaction between DNA and bovine serum albumin (BSA) and the antiproliferative activity of the complexes. My main work is as following:1. We synthesized three types of N-nitrogen heterocyclic demethylcantharate imide: aniline demethylcantharate imide(L’), N-2-pyridine demethylcantharate imide(L2) and N-2-methyl benzimidazole demethylcantharate imide(L3). The composition of them was determined by means of elemental analysis, infrared spectrum, proton nuclear magnetic resonance spectrum. The composition of them were C14H13aNO3(L1), C13H12N2O3(L2), C15H13N2O3(L3). The interaction between the compounds and DNA was studied by means of ultraviolet-visible absorption spectra, fluorescence spectra and viscometric titration. The results showed that the compounds could bind DNA in moderate intensity via partial intercalation. The complexes interaction with bovine serum albumin (BSA) was studied by fluorescence spectra. The complexes could quench the fluorescence of BSA strongly through static quenching. The antiproliferative activitie of the compounds against human cervical cancer cell lines (Hela) was tested with MTT assay in vitro. The antiproliferative activity showed that compound L2and L3have powerful active to Hela than L1. Compound L3has powerful active to Hela.2. The two novel copper complexes:copper(Ⅱ) complex with2-aminomethyl benzimidazole demethylcantharate imide (1) and copper(Ⅱ) complex with norcantharidin and benzimidazole (2) were synthesized by the solution method. Their composition and structures were determined by means of elemental analysis, infrared spectrum and X-ray diffraction. The composition of them were [Cu(Ac)2(L3)2]·3H2O(1)(Ac=acetate, C2H3O2; L3=N-2-methyl benzimidazole demethylcantharate imide, C16H15O3N3),[Cu(bimz)2(DCA)](2)(bimz=benzimidazole, C7H6N2; DCA=demethylcantharate, C8H8O5). Their structures were determined by X-ray diffraction, the coordination numberthe of complex1is four, the coordination center of complex1is quadrangle. The coordination numberthe of complex2is five, the coordination center of complex2is square pyramid. The interaction between the compounds and DNA was studied by means of ultraviolet-visible absorption spectra, fluorescence spectra, viscosity measurements and agarose gel electrophoresis. The interaction between the complexes and bovine serum albumin (BSA) was investigated by fluorescence spectra. The antiproliferative activities of the complexes1and2against human hepatoma cells (SMMC7721) were tested in vitro. The results showed that the compounds could bind DNA in moderate intensity via partial intercalation, and complexes1and2could cleave plasmid DNA through redox mechanism. Complex1and2could quench the fluorescence of BSA strongly through static quenching. Meanwhile, complexes1and2had stronger antiproliferative effect than compound (L3) and Na2(DCA) against human hepatoma cells (SMMC7721) in the tested concentration range. Complex1possessed the most antiproliferative active on human hepatoma cells (SMMC7721).3. Four novel transition metal (Co, Ni, Cu, Zn) complexes of2-aminobenzimidazole (abiz) and demethylcantharate (DCA) were synthesized. Their composition were (Habiz)2[M(DCA)2]-4H2O (M=Co(Ⅱ)(3), Ni(Ⅱ)(4), Cu(Ⅱ)(5), Zn(Ⅱ)(6); Habiz= protonated2-aminobenzimidazole), determined by means of elemental analysis, infrared spectrum and X-ray diffraction. The coordination numberthe of complex3-6is six, the coordination center of complex3-6is octahedron. The DNA binding properties of the complexes were studied by ultraviolet-visible absorption spectra, viscosity measurements and agarose gel electrophoresis, the results showed that the complexes bind DNA in moderate intensity through partial intercalation mode, and the complex5had the most intense binding ability. The interaction with bovine serum albumin (BSA) was studied by fluorescence spectra, the complexes could quench the fluorescence of BSA strongly through static quenching. Complex6possessed strong antiproliferative active on human hepatoma cells (SMMC7721).