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Phosphate derivatives of AZT display enhanced selectivity of action against HIV1 by comparison to the parent nucleoside
Author(s) -
McGuigan Christopher,
Nickson Caleb,
Petrik Juraj,
Karpas Abraham
Publication year - 1992
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(92)81322-d
Subject(s) - selectivity , phosphate , nucleoside , chemistry , zidovudine , action (physics) , combinatorial chemistry , human immunodeficiency virus (hiv) , biochemistry , virology , medicine , viral disease , catalysis , physics , quantum mechanics
Novel phosphate derivatives of the anti‐HIV nucleoside analogue AZT have been prepared by phosphorochloridate chemistry. In particular, phosphates carrying ester‐containing side‐chains are described. These materials are designed to act as membrane‐soluble pro‐drugs of the bio‐active free nucleotides. In vitro evaluation revealed the compounds to have a pronounced, selective antiviral activity. In several cases the phosphate derivatives are more selective in their action than the parent nucleoside AZT. In particular, this arises from the low toxicity of the phosphate pro‐drugs by comparison to AZT. These data support the suggestion that the phosphate derivatives exert their biological effects via intracellular release of the nucleotide forms, and suggests that such pro‐drug, forms may be worthy of further study.