Design of Anti-HIV Compounds from Nucleoside to Nucleoside 5-Triphosphate Analogs. Problems and Perspectives

Author(s): Marina Kukhanova , Alexander Krayevsky , William Prusoff , Yung-Chi Cheng .

Journal Name: Current Pharmaceutical Design

Volume 6 , Issue 5 , 2000

Abstract:

To date, human immunodeficiency virus infection remains incurable although a variety of antiviral agents have been identified and characterized. Even though nucleoside analogs have been the most successful prodrugs, there remains the need to develop new compounds that exhibit a more favorable toxicity profile, less susceptible to cross-resistance, and greater efficacy. As prodrugs, the nucleoside analogs should be sequentially phosphorylated by cellular kinases to yield triphosphate form before they can inhibit HIV replication at the reverse transscriptase level. The efficiency of phospohorylation of nucleoside analogs is a key factor in their antiviral activity and strongly depends on nucleoside structure and cell type. In recent years, several attempts have been made to improve therapeutic potential of nucleoside analogs by the use of nucleotide prodrugs (pronucleotides), that can avoid the first step of phosphorylation. This review focuses on problems of intracellular phosphorylation of nucleoside analogs and perspectives of developing of a new class of nucleotide analogs modified at phosphate group as a form for the delivary of nucleotide analogs into the cell.

Keywords: anti HIV compounds, Nucleoside 5, Triphosphate, immunodeficiency infection, cellular kinases, analogs, inhibit, replication, prodrug, pronucleotides, virus, human, CD4 cell, virion reverse transcriptase, Phosphorylation, Acyclic Nucleoside Phosphonates, Furanosyl, dNMPs, Hydrogenphosphonate derivatives, inhibitors, Anit HIV compounds, pyrophosphorolysis reaction

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Article Details

VOLUME: 6
ISSUE: 5
Year: 2000
Page: [585 - 598]
Pages: 14
DOI: 10.2174/1381612003400687
Price: $58

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