Design, Synthesis and Study of nucleosidic β-modified phosphonate analogs as potential cN-II inhibitors

摘要

Cytosolic 5'-nucleotidase II (cN-II) is one of the seven known mammalian 5'-tiucleotidases that catalyse dephosphorylation of ribo- and deoxyribonucleoside 5'-monophosphates to the corresponding nucleosides and inorganic phosphate1. The enzymes differ in substrate specificity, subcellular location and tissue-specific expression. Thus, intracellular 5'-nucleotidases are likely to affect the phosphorylation level and the pharmacological activity of nucleoside analogues used in the treatment of cancers and viral diseases. In the literature, few studies have dealt with the possible role of cN-II in drug resistance mechanism and M. G. Careddu et al. recently reported that its knockdown causes apoptosis of cultured cancer cells.