Document 0587
 DOCN  M9480587
 TI    Metabolism and mechanism of antiretroviral action of purine and
       pyrimidine derivatives.
 DT    9410
 AU    Balzarini J; Rega Institute for Medical Research, Katholieke
       Universiteit; Leuven, Belgium.
 SO    Pharm World Sci. 1994 Apr 15;16(2):113-26. Unique Identifier : AIDSLINE
       MED/94305498
 AB    Unlike herpes viruses, human immunodeficiency virus and other
       retroviruses do not encode specific enzymes required for the metabolism
       of the purine or pyrimidine nucleotides to their corresponding
       5'-triphosphates. Therefore, 2',3'-dideoxynucleosides and acyclic
       nucleoside phosphonates must be phosphorylated and metabolized by host
       cell kinases and other enzymes of purine and/or pyrimidine metabolism.
       Different animal species (or even different cell types within one animal
       species) may differ in the efficiency of conversion of these drugs to
       their antivirally active metabolite(s). Three 2',3'-dideoxynucleosides
       are officially licensed for clinical use [i.e., zidovudine
       (3'-azido-2',3'-dideoxythymidine, AZT), didanosine
       (2',3'-dideoxyinosine, DDI) and zalcitabine (2',3'-dideoxycytidine,
       DDC)]. A number of other 2',3'-dideoxynucleoside analogues [among them
       stavudine (2',3'-didehydro-2',3'-dideoxythymidine, D4T),
       2',3'-dideoxy-3'-thiacytidine (3TC),
       2',3'-dideoxy-5-fluoro-3'-thiacytidine (FTC) and the acyclic nucleoside
       phosphonate 9-(2-phosphonylmethoxyethyl)adenine (PMEA)] are currently
       under clinical investigation and are candidate compounds for eventual
       licensing as anti-AIDS drugs. The metabolic pathways, antimetabolic
       effects and mechanism of antiviral action of these nucleoside analogues
       will be discussed.
 DE    Animal  Antiviral Agents/*PHARMACOLOGY  Dideoxyadenosine/PHARMACOLOGY
       Dideoxynucleosides/PHARMACOLOGY  Human  Purines/*PHARMACOLOGY
       Pyrimidines/*PHARMACOLOGY  Retroviridae/*DRUG EFFECTS
       Stavudine/PHARMACOLOGY  Thymidine/ANALOGS & DERIVATIVES/PHARMACOLOGY
       Zalcitabine/ANALOGS & DERIVATIVES/PHARMACOLOGY  Zidovudine/PHARMACOLOGY
       JOURNAL ARTICLE  REVIEW  REVIEW, TUTORIAL

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