Zebularine: a unique molecule for an epigenetically based strategy in cancer chemotherapy. The magic of its chemistry and biology.
1-(beta-D-ribofuranosyl)-1,2-dihydropyrimidin-2-one (zebularine) is structurally 4-deamino cytidine. The increased electrophilic character of this simple aglycon endows the molecule with unique chemical and biological properties, making zebularine a versatile starting material for the synthesis of complex nucleosides and an effective inhibitor of cytidine deaminase and DNA cytosine methyltransferase. Zebularine is a stable, antitumor agent that preferentially targets cancer cells and shows activity both in vitro and in experimental animals, even after oral administration.
Marquez
Victor E
VE
Laboratory of Medicinal Chemistry, Center for Cancer Research, NCI at Frederick, NIH, Frederick, MD 21702, USA. marquezv@dc37a.nci.nih.gov
Barchi
Joseph J
JJ
Kelley
James A
JA
Rao
Kambhampati V R
KV
Agbaria
Riad
R
Ben-Kasus
Tsipi
T
Cheng
Jonathan C
JC
Yoo
Christine B
CB
Jones
Peter A
PA
D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D003562:Cytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003564:Cytidine Deaminase / Q000037:antagonists & inhibitors; D004247:DNA / Q000737:chemistry / Q000187:drug effects; D044127:Epigenesis, Genetic; D006801:Humans; D008956:Models, Chemical; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics
D000970:Antineoplastic Agents; D003562:Cytidine; C009131:pyrimidin-2-one beta-ribofuranoside; D004247:DNA; D003564:Cytidine Deaminase