Metal ion complexes of antivirally active nucleotide analogues. Conclusions regarding their biological action

Chemical Society Reviews Pub Date: 2004-02-10 DOI: 10.1039/B310349H

Abstract

Acyclic nucleoside phosphonates (ANPs), i.e., analogues of (2′-deoxy)nucleoside 5′-monophosphates, have been studied during the past 15 years for their potential as antiviral drugs. One of these compounds, 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA; Adefovir) was recently approved in the form of its bis(pivaloyloxymethyl)ester (Adefovir dipivoxil) for use in hepatitis B therapy, a disease evoked by a DNA virus. Diphosphorylated PMEA2?, i.e., PMEApp4?, is initially recognized by nucleic acid polymerases as an excellent substrate, but after insertion in the growing nucleic acid chain, this is terminated due to the lack of a 3′-hydroxy group. Based on the metal ion-binding properties of PMEApp4? it can be explained why the ether oxygen in the aliphatic chain, R–CH2–O–CH2–PO3pp4?, is compulsory for a useful biological activity. Consequently, this critical review presents an overview on the coordination chemistry of various ANPs and correlates this to their biological properties.

Graphical abstract: Metal ion complexes of antivirally active nucleotide analogues. Conclusions regarding their biological action
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