116371-67-6Relevant articles and documents
Synthesis and antitumor activity of a heterodinucleotide of BVDU and gemcitabine
Cappellacci,Franchetti,Vita,Petrelli,Grifantini
, p. 460 - 468 (2008)
A heterodinucleotide comprising BVDU and Gemcitabine bound together by a 5′,5′-pyrophospate bridge (BVDUp2dFdC) has been synthesized and evaluated as antitumor agent against AH13 rat sarcoma cells. BVDUp2dFdC showed a cytotoxicity similar to that of Gemcitabine. Copyright Taylor & Francis Group, LLC.
New Mechanism of Gemcitabine and Its Phosphates: DNA Polymerization Disruption via 3′-5′ Exonuclease Inhibition
Huang, Zhen,Li, Chuncheng,Li, Na,Luo, Danyan,Tang, Shuo,Yang, Shuzhang
, p. 4344 - 4352 (2020/12/03)
Gemcitabine (dFdC), a modified deoxycytidine (dC) widely used in tumor treatment, is a prodrug that is phosphorylated to generate mono-, di-, and triphosphates. The triphosphate (dFdCTP) is incorporated into DNA to terminate DNA synthesis in cancer. Some incorporated dFdC nucleotides can be partially removed by the 3′-5′ exonuclease activity, namely its editing function, and the others escape the editing. However, whether there is an active mechanism for dFdC to escape the editing remains unclear. We have first discovered that unlike dFdC, its mono-, di-, and triphosphates can inhibit the 3′-5′ exonuclease of DNA polymerase I, suppress editing, and allow the active escaping mechanism, whereas its polymerase activity is not remarkably affected. As such, these phosphates can prevent the removal of the incorporated dFdC residue, thereby actively blocking DNA extension and synthesis. The inhibition efficiency of these phosphates follows the increased order of the mono-, di-, and triphosphates of gemcitabine (dFdC a novel anticancer mechanism of gemcitabine and its phosphate derivatives.
Efficient synthesis of gemcitabine 5′-O-triphosphate using gemcitabine 5′-O-phosphoramidate as an intermediate
Kaczmarek, Renata,Radzikowska, Ewa,Baraniak, Janina
supporting information, p. 1851 - 1854 (2014/08/18)
A new efficient approach for the synthesis of gemcitabine triphosphate has been developed. The method is based on the ring-opening reaction of 2-cyanoethoxy-2-oxo-1,3,2-oxathiaphospholane with protected gemcitabine in the presence of DBU. Subsequent treatment of gemcitabine monophosphate with DCC in the presence of ammonia provides gemcitabine 5′-O-phosphoramidate. Finally, this compound, on reaction with pyrophosphate, furnishes gemcitabine 5′-triphosphate in 50% yield. Georg Thieme Verlag Stuttgart. New York.
