| 内容提要: |
5-Fluorouracil (5-FU) has been widely used in the treatment of a range of cancers, including colorectal cancer, breast cancer, and cancers of the aerodigestive tract1. But it is converted intracellularly to several active metabolites: fluorodeoxyuridine monophosphate (FdUMP), fluorodeoxyuridine triphosphate (FdUTP) and fluorouridine triphosphate (FUTP), which will disrupt DNA and RNA synthesis and the action of thymidylate synthase (TS). Therefore, it has some defects such as poor selectivity, drug resistance, and the toxic dose is close to treatment dose.
Saccharide, especially glucose is a major biological nutrient in a variety of cells. Tumor cells show increased uptake of glucose compared to normal tissues, a response mediated by a number of facilitative glucose transporters (GLUTs) located in the cell membrane2. GLUT1, which in most normal tissues is restricted to erythrocytes and blood-tissue barriers, however, overexpressed in many common tumors3.
For these reasons, glycoconjugates of 5-FU has been designed to improve its treatment effects. The synthesis of 1- glycopyranosyl -5-fluorouracil has been reported in some literatures, but it is too cumbersome and time-consuming. Therefore, the synthetic route is optimized in this research. |