Marked inhibitory activity of masked aryloxy aminoacyl phosphoramidate derivatives of dideoxynucleoside analogues against visna virus infection. NLM AIDSLINE Important note: Information in this article was accurate in 1998. The state of the art may have changed since the publication date.

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Marked inhibitory activity of masked aryloxy aminoacyl phosphoramidate derivatives of dideoxynucleoside analogues against visna virus infection.

J Acquir Immune Defic Syndr Hum Retrovirol. 1998 Apr 1;17(4):296-302. Unique Identifier : AIDSLINE MED/98184341
Balzarini J; Cahard D; Wedgwood O; Salgado A; Velazquez S; Yarnold CJ; De Clercq E; McGuigan C; Thormar H; Rega Institute for Medical Research, Katholieke Universiteit Leuven,; Belgium.

Abstract: Lipophilic masked aryloxyaminoacylphosphoramidate derivatives of 2',3'-dideoxynucleoside (ddN) analogues with potent anti-HIV activity (i.e., stavudine [d4T], azidothymidine [AZT], dideoxycytidine [ddC], 3'thio-2',3'-dideoxy cytidine [3TC], dideoxyadenosine [ddA], and 2',3'-didehydro-2',3'-dideoxyadenosine [d4A]) activity were evaluated for their activity against visna virus (VV) in sheep choroid plexus (SCP) cells. The activity of several prodrug derivatives against VV proved markedly superior to that of the corresponding free ddN analogues. In particular, the d4A and ddA prodrug derivatives were exquisitely inhibitory in this model system (50% effective concentration [EC50], < or = 0.003 microM), and their anti-VV potency exceeded by at least 200-fold the antiviral potency of the corresponding free nucleosides. Marked differences were noted in the anti-VV potencies of several of the test compounds depending on the nature of the amino acid linked to the 5'-phosphate moiety, the nature of the nucleoside, or both. In view of the stability of the prodrugs in lamb serum, the VV infection model in lambs may be considered highly useful for investigating the in vivo antiretroviral efficacy of these type of drugs, particularly the d4T, ddA, and d4A prodrug derivatives.
Keywords: *Antiviral Agents/PHARMACOLOGY *Dideoxynucleosides/PHARMACOLOGY *HIV-1/DRUG EFFECTS *Prodrugs/PHARMACOLOGY *Reverse Transcriptase Inhibitors/PHARMACOLOGY *Visna-Maedi Virus/DRUG EFFECTSKWDantiviralagents/pharmacologyKWDdideoxynucleosides/pharmacologyKWDhiv-1/drugeffectsKWDprodrugs/pharmacologyKWDreversetranscriptaseinhibitors/pharmacologyKWDvisna-maedivirus/drugeffects
980630
M9861812

Copyright © 1998 - National Library of Medicine. Reproduced under license with the National Library of Medicine, Bethesda, MD.

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