The Electrochemical Study Of Anticancer Drug And Interaction With DNA

It is well known that anticancer drugs have become increasingly important in the treatment of tumor.In view of their inherent risk of toxicity,the development of highly sensitive and selective analytical methods for measuring anticancer drugs is therefore necessary. Moreover Deoxyribonucleic acid (DNA) is the primary target molecule for most of anticancer dnig.So the study of interaction between anticancer drug and DNA is helpful not only to understand the action mechanisms of some antitumor drugs.but also to the design of artificial DNA-targeting drug molecule. In this paper, the electrochemical behavior of the anticancer drugs Methotrexate(MTX) and Colchicine(COLC) have been studied. The interaction between 6-Mercaptopurine (6-MP) and DNA have been studied too. The main results are expressed as below:1. The electrochemical characteristics of methotrexate are studied by using different electrochemical methods at the mercury drop electrode. In Britton-Robinson buffer solution (pH9.20), a pair of redox peaks of methotrexate controlled by adsorption is obtained by cyclic voltammetry. The differential pulse voltammetry peak current is proportional to the concentration of methotrexate in the range of 1.0 10-5 mol/L~ 5.0 10-8mol/L with the detection limit of 5.0 X 10-9mol/L, which has been used in real sample analysis with satisfactory result. Moreover, the electrode reaction mechanism of the system are studied and the kinetic parameters are obtained too.The electrode reduction of MTX is a quasi-reversible process with two electrons and two protons.2. The electrochemical behavior of colchicine is studied at the glassy carbon electrode. In 0.2mol/L HAc-NaAc buffer (pH4.60), an oxidative peak of COLC is obtained by cyclic voltammetry. The peak potential is at 1.22V(vs.SCE). The anodic peak current obtained by differential pulse voltammetry is proportional to the concentration of COLC in the range of 8.0 10'7mol/L~ 1.0 10-5mol/L with the detection limit of 1.0 10-7mol/L.The proposed method has been applied to the determination of COLC in human serum with satisfactory result. Moreover, the electrodereaction mechanism of the system are studied and some kinetic parameters are obtained too.3. The electrochemical studies of interaction between 6-mercaptopurine and DNA are performed in 0.2mol/L HAc-NaAc buffer (pH5.6). Both reduction and oxidation peak currents decrease and the peak potentials also shift positively with the increasing of time and DNA concentration respectively. The result shows the reaction of DNA with 6-MP have formed an electrochemically non-active complex. The composition of the complex is 1:1. The combining constant is 5.17 106 .Simultaneously, the electrode reaction process have been investigated by electrochemical techniques, and its dynamic parameters have been obtained too.The decrease in peak current is proportional to DNA concentration and can be used to determine DNA concentration.