Studies On The Interactions Between Anthracyline Disaccharides With Ctdna

Cancer is one of the diseases which is most difficult to cure .It is an efficiency method to find more efficiency new anticancer drugs. Scientists observed that all the anticancer drugs interact with deoxyribonucleic acid (DNA). Studies on the interactions between DNA and anticancer drugs are of great importance. The studies can throw some light on the pharmacological mechanisms of the drug and administer to screen the drugs in vitro. For designing the anticancer drugs of high-performance and low toxicity, the studies can provide substantial theoretical foundation and right direction guidance.The anthracycline antitumor drugs daunomycin is potent anticancer drugs employed in chemotherapy. So far, daunorubicin are considered to be most important agents in use in cancer chemotherapy. However, drug resistance and cardiotoxicity of anthracyclines limit their clinical application. Many researchers have explored to modify the structure of anthracycline to generate more analogs to reduce the side effects and reverse multidrug resistance; however, these efforts only have limited success. Professor Zhang Guisheng laboratory developed DNR-D2, DNR-D3, DNR-D4, DNR-D5 and so on several derivatives of daunorubicin.This study was designed to examine the interaction of these anthracycline disaccharides, with calf thymus deoxyribonucleic acid ctDNA by UV/Vis in combination with fluorescence spectroscopy and molecular modeling techniques under physiological conditions (Britton–Robinson buffer solutions, pH = 7.4). Thses results which from our expermiment suggest that the sugar plays a vital role in the binding of anthracycline disaccharide with ctDNA. Moreover, the 2, 6-dideoxy withα-linkage to the first sugar of anthracycline disaccharide exhibit better anticancer activity thanβ-linkage to the first sugar of anthracycline disaccharide. These results have provided useful insights into drug-DNA interactions. In particular, it partly direct the discovery of derivatives or methodology which will maximize tumor response and minimize side effect, especially the acute cardiotoxicity.