1,4 - Dihydropyridine Derivatives And Dna Interactions

1,4-dihydropyridine(1,4- DHP) derivatives are a kind of extensively applied drugs for reducing the blood pressure. It was found that this kind of drugs produces the medical efficacy only after they were oxidated by cytochrome P-450 in the liver during the metabolism in the human body. Therefore, the oxidation process of 1,4- DHP derivatives has been attracted the considerable attention. Secondly, the medical efficacy of many drugs is produced through the interaction between the drug and DNA. Thus, the study of the interaction between a drug and DNA is very important for understanding the mechanism of medical action, proceeding the extracorporeal filtration of drugs, reconstructing the structures of drugs with the relationship between the structure and medical efficacy and designing new drugs with high medical efficacy and low side-effect. In this thesis, using the spectroscopic and electrochemical methods, the electrochemical behaviors of 1,4-DHP derivatives were studied and summarized the effects of the substituent groups of 1,4- DHP derivatives and solvent on the electrochemical behaviors of 1,4- DHP derivatives were summarized. Based on it, the changes in their electrochemical properties before and after the interaction of 1,4- DHP derivatives with DNA were investigated. The differences of the interactions of 1,4-DHP derivatives with different substituent groups with DNA were compared. It will offer some experimental basises for the relationships of structures of drugs with their medical efficacy. The main results obtained are as follows.1 .The electrochemical reaction of the dihydropyridine group of 1,4- DHP derivatives is irreversible at the glassy carbon electrode. The results of Raman spectroscopy demonstrated that when the electrochemical reactions of the 1,4- DHP derivatives occur, their dihydropyridine groups will lose two protons and two electrons forming the pyridine derivatives.2.The anodic and cathodic peak potentials of the dihydropyridine groups of 1,4- DHP derivatives relate to the electron-accepting ability of 4-substituents of the dihydropyridine groups. When the electron-accepting ability increases, the density ofthe electron cloud of the dihydropyridine groups decreases, so that the dihydropyridine group is easy to be reduced and difficult to be oxidized. Thus, the anodic peak potential shifts to the positive direction and the cathodic peak potential shifts to the negative direction. The results of cyclic voltammograms showed that the anodic peak current is much more larger than the cathodic peak current, proving that the oxidation of the dihydropyridine groups is easier than their reduction. Therefore, the effect of the electron-accepting ability of the 4-substituents on the oxidation reaction is larger than that the reduction reaction. Thus, when the electro-accepting ability increases, the difference between the anodic and cathodic peak potentials. AEp of the dihydropyridine groups decreases, illustrating that the reversibility of the electrochemical reactions of the dihydropyridine groups increases.3.The electrochemical behaviors of the dihydropyridine group of 1,4- DHP derivatives is related the properties of the solvent. Firstly, in the organic solvent without water, the electrochemical irreversibility of the dihydropyridine group of 1,4- DHP derivatives is larger than that in the organic solvent with water. It is due to that the electrochemical reaction of the dihydropyridine group is related to obtaining or losing the protons. Secondary, in some organic solvent without water, such as CH3CN, the dihydropyridine group of 1,4- DHP can proceed the irreversible electrochemical reaction, but in CHCI3 without water, no electrochemical reaction of the dihydropyridine group can be observed. It maybe related to the polarity and conjugation of the solvent molecules. 4.After 1,4- DHP derivatives interact with calf thymus DNA (CT-DNA), their anodic peak potentials shift to the positive direction, indicating that 1,4- DHP derivatives can intercalate into the double-strand of CT-DNA. Th...