Synthesis, cytostatic activity and inhibition of ribonucleotide reductase by 5'-phosphoramidates and 5'-diphosphates, of 2'-O-allyl-arabinofuranosyl nucleosides

S Manfredini; P G Baraldi; E Durini; J Balzarini; E De Clercq; A Karlsson; V Buzzoni; L Thelander

doi:10.1080/15257779908041631

Synthesis, cytostatic activity and inhibition of ribonucleotide reductase by 5'-phosphoramidates and 5'-diphosphates, of 2'-O-allyl-arabinofuranosyl nucleosides

Nucleosides Nucleotides. 1999 Apr-May;18(4-5):1007-8. doi: 10.1080/15257779908041631.

Authors

S Manfredini¹, P G Baraldi, E Durini, J Balzarini, E De Clercq, A Karlsson, V Buzzoni, L Thelander

Affiliation

¹ Department of Pharmaceutical Sciences, Ferrara University, Italy.

PMID: 10432732
DOI: 10.1080/15257779908041631

Abstract

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.

MeSH terms

Animals
Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / pharmacology
Cell Division / drug effects
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / pharmacology*
Mice
Nucleosides / chemical synthesis*
Nucleosides / pharmacology*
Organophosphorus Compounds / chemistry
Ribonucleotide Reductases / antagonists & inhibitors*

Substances

Antineoplastic Agents
Enzyme Inhibitors
Nucleosides
Organophosphorus Compounds
Ribonucleotide Reductases