Research On The Interaction Between Flavonoids And DNA Or Its Constituted Basic Group

The essential biological materials — DNA has been playing many vital roles for all kinds of biological phenomena. Exploring the interaction mechanisms on these bio-macromolecules with small molecules or ions, especially for those drug molecules, at the molecular level is of current interest in many research areas such as biology, clinical medicine, medicinal chemistry, chemistry and so on. The present thesis consists of the following four parts.In the first part, we introduce the structure, the property and the biological and pharmacological activity of flavonoids. Then the developments of the research on the interaction between biomacromolecule-DNA and little molecules in recent years have been expatiated. We induce the interaction's model and characters, sum up the research methods and instruments. And also the importance of the research in biology, medicine and chemistry has been analyzed.In the second part, through Isothermal Titration Calorimetry (ITC) on the LKB-2277 Thermal Activity Monitor we research the interaction between adenine, pyrimidine, guanine, cytosine, purine and 11 flavonoids receive the combining data and interaction's thermodynamic data. We find that there are great differences in adenine, pyrimidine, guanine, cytosine, purine reacting with flavonoids respectively. After analyzing these data, we run the conclusion that the nitrogen atom on the No.9 site in adenine, nitrogen atom on the No.9 site and carbonyl on the No.6 in guanine, nitrogen atom on the No.1 site and carbonyl on the No.2 in cytosine, react with flavonoids is the main reaction sites. At the same time we also find that aromatic hydrogen bonds are affected by molecule's steric effect in some flavonoids such as quercetin, luteolin, myricetin, rutin reacting with adenine. But the reaction can be strengthened by hydrogen bonds between the phenolic hydroxyl group in this flavonoids and carbonyls in guanine and cytosine.Moreover the UV spectrum is also used to determinate the interaction between adenine, pyrimidine, guanine, cytosineand flavonoids. The results indicate that the addition of pyrimidine does not bring the movement of the peak of flavone, but theaddition of adenine, guanine and cytosine bring the movement of the peak. And the comparisons of the UV spectrum between guanine, cytosineand adding quercetin and morin, shows that the conclusions get from ITC is correct.In the third part, to be the base of the later research, the interactions between dsDNA, hsDNA and flavonoids are researched by ITC and receive the combining data and interaction's thermodynamic data. After analyzing the data we discover that the planarity of flavonoids allows it to penetrate the DNA helix and to arrange its planar structure more or less parallel to the adjacent planes of the nitrogenous bases. So the hydrogen bonds can be formed between the phenolic hydroxyl group in B ring and carbonyls in guanine and cytosine. Because herring sperm DNA is B-DNA similarly which its major groove is narrow and deep, the hydrogen bonds can not formed.In the fourth part, 13 flavonoids were studied as scavengers of superoxide anion. By comparison of the standard molar reaction enthalpies of flavonoids scavenging superoxide anion, which were measured on microcalorimetry, it is clear that not only flavonoids are the compounds as inhibitors of non-enzymic lipid peroxidation, but also the ability of the resistance to oxidation is distinctly affected on the structure of flavonoids. The experimental results show that with the increase of the phenolic hydroxyl groups, the flavonoids scavenging ability to superoxide anion is stronger, the position of phenolic hydroxyl groups in the flavonoid molecules and presence of 2,3-double bond in the C-ring obviously affect the antioxidation activity of flavonoids, and the most potent scavenger of flavonoids should have ortho-dihydroxyl groups on B-ring of flavonoids.Through several methods, we research the interaction between the DNA, the nitrogenous bases of D1\A and flavonoids receive the combining data and interaction's thermodynamic. From these data, we get an innovative conclusion that different flavonoids interact with DNA and its nitrogenous bases in different reaction site.