Studies On The Syntheses, Structures And In Vitro Antitumor Activities Of Metal Complexes Based On Biological Macromolecules

Cancer has become the second largest killer to human health at this moment and chemotherapy throughout the cancer treatment. Thus, it is urgent to find the effective and safe drugs to cure the cancer. Among various anticancer drugs,cis-platin can bind to DNA in covalent interaction to restrain cancer cell.But the side-effects of cis-platin limit its further application. The design and synthesis of non-platinum metal-bsaed anticancer drugs is significant to find more broad-spectrum, more-efficacious and less-toxic anticancer metal complexes. Baesd on the above considerations, a series of complexes have been synthesized and five metal complexes were synthesied and characterized by X-ray single crystal diffraction. The binding ability of the complexes with DNA. BSA and carbohydrate were studied by spectra methods. The in vitro anticancer activities were further investigated. The detailed contents mainly include the following parts:1. Synthesis and structures of complexes:Five complexes were synthesized by choosing N,N’-bis(dipropylenetriamine)oxamide (H2oxdipn) and dipropylentriamin (dipn) as the ligands with different kinds of metal salts, namely [Cu(dipn)(pic)](pic) (1), [Cu2(oxdipn)](pic)2 (2), [Cu2(oxdipn)(ClO4)2] (3), [Cu2(oxdipn)][Cu(SCN)2]2 (4) and{[Cu4(oxdipn)2Fe(CN)5(NO)][Fe(CN)5(NO)]}n·3.5nH2O (5). The five complexes were characterizeed by elemental analyses, molar conductance measurements, IR and X-ray single crystal diffraction.2. The interaction of the complexes with biological macro molecules:In order to investigat the factors of complexes on biological macro molecules binding properties, various methods were applied in this onvestigation.The five complexes can interact with the DNA in the mode of intercalation, revealing that the number of metal ion and counterions can affect the DNA-binding properties for complexes. The protein binding abilities of the five complexes have been monitored by using UV absorption and tryptophan fluorescence quenching experiment, suggesting that the five complexes can effectively quench the intrinsic fluorescence of BSA via a static mechanism. Additionally, the interaction of complexes with carbohydrate was investigated by UV absorption.The results reveal that the complexes can bind the carbohydrate with different afinities, and of which the ability of glucosamine is the strongest. The binding ability of the monosaccharide with metal complexes is closely related to the number of metal ions, the stability of chelate rings and the steric of the countenons.3. In vitro anticancer activities of complexes:The in vitro anticancer activities of complexes 1-5 against three cancer cell lines by SRB method. The results indicate that all of the complexes exhibit cytotoxic effects against the selected tumor cell lines SMMC-7721, Hep G2 and A549. The anticancer activities can be affected by the number of metal ions and the counterions. And the order is consistent with their DNA-binding abilities. The results attest that DNA is the target of the metal complexes.