1147100-77-3Relevant academic research and scientific papers
N-Acyl-phosphoramidates as potential novel form of gemcitabine prodrugs
Baraniak, Janina,Pietkiewicz, Aleksandra,Kaczmarek, Renata,Radzikowska, Ewa,Kulik, Katarzyna,Krolewska, Karolina,Cieslak, Marcin,Krakowiak, Agnieszka,Nawrot, Barbara
, p. 2133 - 2140 (2014)
Gemcitabine (dFdC) is a cytidine analog remarkably active against a wide range of solid tumors. Inside a cell, gemcitabine is phosphorylated by deoxycytidine kinase to yield gemcitabine monophosphate, further converted to gemcitabine di- and triphosphate. The most frequent form of acquired resistance to gemcitabine in vitro is the deoxycytidine kinase deficiency. Thus, proper prodrugs carrying the 5′-pdFdC moiety may help to overcome this problem. A series of new derivatives of gemcitabine possessing N-acyl(thio)phosphoramidate moieties were prepared and their cytotoxic properties were determined. N-Acyl-phosphoramidate derivatives of gemcitabine have similar cytotoxicity as gemcitabine itself, and have been found accessible to the cellular enzymes. The nicotinic carboxamide derivative of gemcitabine 5′-O-phosphorothioate occurred to be the best inhibitor of bacterial DNA polymerase I and human DNA polymerase α.
