Biological activity and phosphorylation of 2'-azido-2'-deoxyuridine and 2'-azido-2'-deoxycytidine.
2'-Azido-2'-deoxyuridine and 2'-azido-2'-deoxycytidine were evaluated for their inhibitory activity against ribonucleotide reductase and for subsequent cell growth inhibition. Their mono- and di-phosphates were synthesized and their inhibitory activities against the reductase were also determined in a permeabilized cell system, along with the two nucleosides. The results of the present study identify the first phosphorylation step involved in the conversion of the two azidonucleosides to the corresponding diphosphates to be rate-limiting in the overall activation.
School of Pharmacy, University of North Carolina, Chapel Hill 27514, USA.
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Kang
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Cho
D000818:Animals; D001386:Azides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D016466:CHO Cells; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D006224:Cricetinae; D003562:Cytidine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D003857:Deoxyuridine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D010766:Phosphorylation; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors*; D013056:Spectrophotometry, Ultraviolet
D001386:Azides; D004791:Enzyme Inhibitors; C114286:2'-azido-2'-deoxyuridine; C015010:2'-azidocytidine; D003562:Cytidine; D012264:Ribonucleotide Reductases; D003857:Deoxyuridine