Synthesis, Structure And Interaction With DNA/BSA Of Demethylcantharate And Imidazole Derivatives Transition-Metal Complexes

Currently, studying anticancer drugs is a hot spot in the field of biochemistry research. Now, there are three type anticancer drugs used generally at home and abroad: interact directly with DNA; obstruct protein synthesis and inhibit nucleic acid synthesize. Cantharidin (CA) is a compound which exists in Chinese blister beetle. However with a lot of bioactivity, it has strong cytotoxicity. After Gilbert Stork synthesized CA at 1951, the structure of cantharidin was modified by many people. Some compounds with high-activity and low-cytotoxicity were designed and synthesized such as norcantharidin. Norcantharidin (NCTD) possesses anticancer activity and stimulates the bone marrow, but reduces the cytotoxicity greatly.We have designed and synthesized novel demethylcantharate and imidazolium compounds transition-metal complexes. We also have studied the interaction between calf thymus DNA (ct-DNA) and bovine serum albumin (BSA) and the antiproliferative activity of the complexes. The main work is as following:1. Four new mixed-ligand complexes:[Ni(BIM)(DCA)(H2O)]·2H2O(1), [Zn2(BIM)2(DCA)2]·8H2O(2), [Cu2(BIM)2(DCA)2]-H2O(3), [Co2(BIM)2(DCA)2]-4H2O(4) (BIM=2-(aminomethyl)benzimidazole, C16H17N3; DCA2-=demethylcantharate, C8H8O5) were prepared and characterized by elemental analysis, molar conductance, IR and TG-DTG. The structures of the complexesl-3 were determined by X-ray diffraction. The DNA binding of the complexes were investigated by electronic absorption spectra, fluorescence, thermal denaturation studies, and viscosity measurements; the interaction with bovine serum albumin (BSA) was studied by fluorescence spectra. The antiproliferative activities of the complexes against human hepatoma cells(SMMC7721) and gastric cancer cells(MGC80-3) in vitro were evaluated with MTT assay. The results showed the complexes had a partial intercalation with DNA and the binding activity with DNA of complex3 was strongest. The BSA experiments showed that quenching of complexes to BSA was mainly a static quenching process, formed 1:1 compound with BSA and transformed the conformation of BSA. The binding activity with BSA is complex4>complexl>complex3>complex2. The antiproliferative activity showed that all the complexes have powerful active to SMMC7721 and were stronger than Na2DCA. Complex2 and complex3 have powerful active to MGC80-3 stronger than Na2DCA.2. Two mixed-ligand complexes: Ni(IM)(DCA)(2H2O)]·2H2O(5), Cd2(IM)4(DCA)2]·2H2O(6) (IM=imidazole, C3H4N2; DCA2-=demethylcantharate, C8H8O5) were prepared and characterized by elemental analysis, molar conductance, IR and TG-DTG. The structures were determined by X-ray diffraction. The DNA binding of the complexes were investigated by electronic absorption spectra, fluorescence and viscosity measurements, the interaction with bovine serum albumin(BSA) was studied by fluorescence spectra. The antiproliferative activities of complexes against human hepatoma cells(SMMC7721) and human breast carcinoma cells(MCF-7) in vitro were evaluated with MTT assay. The results showed all the complexes had a partial intercalation with DNA and the binding activity with DNA of complex5 was stronger than complex6. The BSA experiments showed that quenching of complexes to BSA was mainly a static quenching process, formed 1:1 compound with BSA and transformed the conformation of BSA. The binding activity with BSA is complex5> complex6. The antiproliferative activity showed that all the complexes had powerful active to SMMC7721 and were stronger than Na2DCA, but the active to MCF-7 of the complexl and complex5 was weaker than Na2DCA...