title: Synthesis and evaluation of some novel phosphate and phosphinate derivatives of araA. Studies on the mechanism of action of phosphate triesters.
abstract: A number of novel phosphinate and phosphate triester derivatives of the anti-viral nucleoside analogue araA have been prepared. Spectroscopic and analytical data have been collected on both the reagents and the nucleotides. An in vitro assay indicated inhibition of DNA synthesis by mammalian cells, by each of the nucleotide derivatives, in the range 3-30 microM. Inhibition was reduced, but not abolished, for the phosphinates relative to the phosphates. These results are consistent with a mode of action involving release of the free nucleoside araA and the nucleotide araAMP.
authors.affiliation: Department of Chemistry, University College London, UK.
authors.forename: C
authors.initials: C
authors.lastname: McGuigan
authors.forename: J M
authors.initials: JM
authors.lastname: Shackleton
authors.forename: S M
authors.initials: SM
authors.lastname: Tollerfield
authors.forename: P A
authors.initials: PA
authors.lastname: Riley
mesh_terms: D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D004247:DNA / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D015394:Molecular Structure; D010710:Phosphates; D010721:Phosphinic Acids; D013329:Structure-Activity Relationship; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology
chemical_list: D010710:Phosphates; D010721:Phosphinic Acids; D004247:DNA; D014740:Vidarabine