Prodrug strategies for antiviral drugs

Structurally modified nucleotides have received attention as a means to combat against viral infections, cancer and hereditary diseases. The research is focused on pro-drug models of nucleotides. The goal is to develop the degradable lipophilic carriers which are used to improve the cellular membrane penetration of the negatively charged nucleotides. To obtain mechanistic information on the chemical hydrolysis and enzymatic cleavage of the protecting groups, the kinetic studies of the pro-drugs are of interest.


Hematological malignancies can be treated by cytotoxic drugs, which chemically resemble nucleosides, the building blocks of DNA and RNA. One of the most important drugs of this type, pentostatin, is used to treat leukemia. Since ADA2 has a strong growth factor activity for several types of immune cells, its inhibition may facilitate the treatment of leukemia. The purpose of this study is to prepare the first ADA2-specific inhibitor, structurally modified pentostatin derivative. 

The small RAS oncoproteins play a crucial role in human cancers and are, hence, a target in anticancer drug discovery. In spite of numerous efforts, a direct small-molecule signalling inhibitor drug of mutant RAS has not been able to develop. The aim of the study is to provide a potent method to suppress oncogenic RAS signalling with coumarin phosphotriester derivatives.