Organic Chemistry

The goal is preparation of structurally modified 5-azacytosine nucleosides and their analogues - compounds with epigenetic (hypomethylating) activity, currently used in cancer therapy.  These modifications will involve e.g. substitutions of the 5-azacytosine moiety by 5,6-dihydro-5-azacytosine, imidazo[1,2-a][1,3,5]triazine, pyrimido[1,2-a][1,3,5]triazine a other  five-membered heterocycles, bases mimicking 5-azacytosine and 5,6-dihydro-5-azacytosine. The final aim of this work is finding structures with better pharmacological profile (lower toxicity) compared to 5-azacytidine but still preserving their hypomethylating activity. The ability of new compounds to be incorporated to DNA/RNA and  implicate mutations will be also studied.