Potent inhibitors for the deamination of cytosine arabinoside and 5-aza-2'-deoxycytidine by human cytidine deaminase

Cancer Chemother Pharmacol. 1992;30(1):7-11. doi: 10.1007/BF00686478.


Deamination of the nucleoside analogues ARA-C and 5-AZA-CdR by CR deaminase results in a loss of antileukemic activity. To prevent the inactivation of these analogues, inhibitors of CR deaminase may prove to be useful agents. In the present study we investigated the effects of the deaminase inhibitors Zebularine, 5-F-Zebularine, and diazepinone riboside on the deamination of CR, ARA-C, and 5-AZA-CdR using highly purified human CR deaminase (EC These inhibitors produced a competitive type of inhibition with each substrate, the potency of which followed the patterns diazepinone riboside greater than 5-F-Zebularine and THU greater than Zebularine. 5-AZA-CdR was more sensitive than ARA-C to the inhibition produced by these deaminase inhibitors. The inhibition constants for diazepinone riboside lay in the range of 5-15 nM, suggesting that this inhibitor could be an excellent candidate for use in combination chemotherapy with either ARA-C or 5-AZA-CdR in patients with leukemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / metabolism*
  • Azacitidine / analogs & derivatives*
  • Azacitidine / metabolism
  • Azepines / pharmacology
  • Cytarabine / metabolism*
  • Cytidine / analogs & derivatives
  • Cytidine Deaminase / antagonists & inhibitors*
  • Deamination / drug effects
  • Decitabine
  • Humans
  • Kinetics
  • Pyrimidine Nucleosides / pharmacology
  • Tetrahydrouridine / pharmacology


  • Antineoplastic Agents
  • Azepines
  • Pyrimidine Nucleosides
  • Cytarabine
  • Tetrahydrouridine
  • Cytidine
  • 5-fluoropyrimidin-2-one beta-ribofuranoside
  • diazepinone riboside
  • Decitabine
  • pyrimidin-2-one beta-ribofuranoside
  • Cytidine Deaminase
  • Azacitidine