Synthesis, cytostatic activity and inhibition of ribonucleotide reductase by 5'-phosphoramidates and 5'-diphosphates, of 2'-O-allyl-arabinofuranosyl nucleosides.
The diphosphates of a series of 2'-O-allyl-1-beta-D-arabinofuranosyl derivatives, previously obtained by us, have been prepared and tested for their inhibitory activity in an in vitro assay using R1 and R2 subunits of the purified recombinant mouse ribonucleotide reductase (RNR). 2'-O-Allyl-araU diphosphate proved to be inhibitory, with an IC50 of 100 microM. The 5'-phosphoramidate pronucleotide of 2'-O-allyl-araU was also prepared and tested for inhibition of tumor cell proliferation.
Manfredini
S
S
Department of Pharmaceutical Sciences, Ferrara University, Italy.
Baraldi
P G
PG
Durini
E
E
Balzarini
J
J
De Clercq
E
E
Karlsson
A
A
Buzzoni
V
V
Thelander
L
L
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D051379:Mice; D009705:Nucleosides / Q000138:chemical synthesis* / Q000494:pharmacology*; D009943:Organophosphorus Compounds / Q000737:chemistry; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors*
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D009705:Nucleosides; D009943:Organophosphorus Compounds; D012264:Ribonucleotide Reductases