Advertisement

 

 

Virtual screening of acyclovir derivatives as potential antiviral agents: design, synthesis and biological evaluation of new acyclic nucleoside ProTides.

Virtual screening of acyclovir derivatives as potential antiviral agents: design, synthesis and biological evaluation of new acyclic nucleoside ProTides.
Author Information (click to view)

Derudas M, Vanpouille C, Carta D, Zicari S, Andrei G, Snoeck R, Brancale A, Margolis L, Balzarini J, McGuigan C,


Derudas M, Vanpouille C, Carta D, Zicari S, Andrei G, Snoeck R, Brancale A, Margolis L, Balzarini J, McGuigan C, (click to view)

Derudas M, Vanpouille C, Carta D, Zicari S, Andrei G, Snoeck R, Brancale A, Margolis L, Balzarini J, McGuigan C,

Advertisement

Journal of medicinal chemistry 2017 08 22() doi 10.1021/acs.jmedchem.7b01009

Abstract

Following our findings on the anti-human immunodeficiency virus (HIV) activity of acyclovir (ACV) phosphate prodrugs, we herein report the ProTide approach applied to a series of acyclic nucleosides aimed at the identification of novel and selective antiviral, in particular anti-HIV agents. Acyclic nucleoside analogues used in this study were identified through a virtual screening using HIV-reverse transcriptase (RT), adenylate/guanylate kinase, and human DNA polymerase. A total of thirty-nine new phosphate prodrugs were synthesised and evaluated against HIV-1 (in in vitro and in ex-vivo human tonsillar tissue system) and human herpes viruses. Several ProTide compounds showed substantial potency against HIV-1 at low micromolar range while the parent nucleosides were not effective. Also, pronounced inhibition of herpesvirus replication was observed. A carboxypeptidase-mediated hydrolysis study was performed for a selection of compounds to assess the formation of putative metabolites and support the biological activity observed.

Submit a Comment

Your email address will not be published. Required fields are marked *

eighteen + fifteen =

[ HIDE/SHOW ]