Synthesis of modified uracil derivatives and their potential use as prodrugs
Santrauka
Fluorinated derivatives of uracil and uridine can act as prodrugs in the cancer therapy. The chemical synthesis of 5-fluoroisocyto-sine and the fluorinated 20-O-methyluridine was performed. 5-Fluorouridine and 5-fluorodeoxyuridine were obtained by the enzymatic synthesis using thymidine phosphorylase (EC 2.4.2.4) from Escherichia coli. Thymidine phosphorylase mediates the nucleobase-exchange reaction to convert thymidine or uridine to modified nucleosides possessing a functional group at the 5th position and allows biosynthesis of modified nucleosides that are not possible to obtain by organic synthesis methods. The obtained compounds were converted into the 5-fluorouracil, a cancer drug, by action of newly discovered enzymes, such as iso-cytosine deaminase and nucleoside hydrolase. In conclusion, it was demonstrated that the synthesized fluorinated uracil derivatives could be used as prodrugs in the cancer therapy