Investigation On Synthesis, Characterization And Biological Activity Of 3 Kinds Of Flavonoid-Cu(II) Complexes

Flavonoids are the effective chemical compositions of many commonly used chinese herbal medicine. Flavonoids have been reported to possess antibacterial, anti-inflammatory, antiallergic, antihepatotoxic, antiatherogenic, cardiovascular protection, diuretic and sedative activities. They also have the potential beneficial effects of antioxidative, anticarcinogenic and inhibition activity on lipase. In addition, flavonoids are also important functional food additives, such as natural antioxidants, natural pigments, natural sweeteners, and so on. Flavonoids are composed of two aromatic rings linked through three carbon atoms that form an oxygenated heterocycle. Due to a convenient position of the 5-OH and 4-CO groups in a molecule, the structure composes a largeπ- bond conjugation system, of which the oxygen atoms has a potential activity to chelate with metal ions. It will contribute to be a new pharmacological effect or to increase their efficacy when flavonoids chelated with some microelements that have bioactivity and pharmacological activity themselves. Therefore, the research of flavonoids metal complexes, will help us to develop and utilize flavonoids from a new viewpoint of novel natrue compound and metal-based drug. Flavonoid compounds, apigenin, hesperetin and naringenin that with pharmacological effect were choosed as organic ligand, then their copper complexes were synthesized, characterized, and their DNA-binding properties, anti-cancer activities were investigated. The main content consists of four chapters:In chapter 1: A review was presented, in wich introduced the research development and orientation about coordination chemistry of traditional chinese medicine. The structural characteristics and their metal complexes of flavonoids were reviewed.In chapter 2: The Cu(II) complex of apigenin, hesperetin and naringenin were synthesized and characterized by IR, ICP, elementary and thermogravimetry analysis. The composition and structure of the complexes were determined.In chapter 3: First, the structure of DNA, the mechanisms of metal complexes with DNA and the research methods of the interaction between metal complexes with DNA were described. Then, the mechanism of the interaction between the free ligand and complexes with calf thymus DNA (ct-DNA) was investigated by using means of UV spectra, fluorescent spectra and CD spectra. The experimental results suggested that both the ligand and the complexes can insert between DNA base pairs and that the complexes can bind to DNA more strongly than just the free ligand.In chapter 4: The anti-cancer activities of the free ligand and complexes against eight kinds of common human tumor cell lines were tested. The results showed that: the inhibited activity of Hsp-Cu and Apg-Cu complex against liver cancer HePG-2, gastric cancer SGC-7901, nasopharyngeal cancer cells CNE1, Hela cells of human was significantly stronger than ligand; Apg-Cu complex expressed more efficient inhibited activity on Ketr-3 cells than Apg; and the inhibited activity of Nrg-Cu complex against liver cancer HePG-2, Ketr-3, nasopharyngeal cancer cells CNE1 is obviously stronger than the free ligand Nrg.