Pharmacy World and Science

, Volume 16, Issue 2, pp 113–126 | Cite as

Metabolism and mechanism of antiretroviral action of purine and pyrimidine derivatives

  • Jan Balzarini
Purine and Pyrimidine Metabolism

Abstract

Unlike herpes viruses, human immunodeficiency virus and other retroviruses do not encode specific enzymes required for the metabolism of the purine or pyrimidine nucleosides 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.

Keywords

Acquired immunodeficiency syndrome Antiviral agents Dideoxynucleosides Drug development HIV Nucleoside phosphorates, acyclic Phosphonylmethoxyelhyladenine Reverse transcriptase TSAO 

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Copyright information

© Royal Dutch Association for the Advancement of Pharmacy 1994

Authors and Affiliations

  • Jan Balzarini
    • 1
  1. 1.Rega Institute for Medical ResearchKatholieke Universiteit LeuvenLeuvenBelgium

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