Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

Synthesis and biological evaluation of pyrimidine nucleoside monophosphate prodrugs targeted against influenza virus

Meneghesso, Silvia, Vanderlinden, Evelien, Stevaert, Annelies, McGuigan, Christopher, Balzarini, Jan and Naesens, Lieve 2012. Synthesis and biological evaluation of pyrimidine nucleoside monophosphate prodrugs targeted against influenza virus. Antiviral Research 94 (1) , pp. 35-43. 10.1016/j.antiviral.2012.01.007

[img]
Preview
PDF
Download (18MB) | Preview

Abstract

Uridine-based nucleoside analogues have often been found to have relatively poor antiviral activity. Enzymatic assays, evaluating inhibition of influenza virus RNA polymerase, revealed that some uridine triphosphate derivatives displayed inhibitory activity on UTP incorporation into viral RNA. Here we report the synthesis, antiviral activity and enzymatic evaluation of novel ProTides designed to deliver the activated (monophosphorylated) uridine analogues inside the influenza virus-infected cells. After evaluation of the activation profile we identified two ProTides with moderate antiviral activity in MDCK cells (23a, EC99 = 49 ± 38 μM and 23b, EC99 ⩾ 81 μM) while the corresponding nucleoside analogue (2′-fluoro-2′-deoxyuridine) was inactive. Thus, at least in these cases the poor antiviral activity of the uridine analogues may be ascribed to poor phosphorylation.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Pharmacy
Systems Immunity Research Institute (SIURI)
Subjects: R Medicine > RM Therapeutics. Pharmacology
R Medicine > RS Pharmacy and materia medica
Uncontrolled Keywords: Uridine-based nucleoside analogues; ProTide; RNA polymerase; Carboxypeptidase Y
Publisher: Elsevier
ISSN: 0166-3542
Last Modified: 20 Oct 2017 09:23
URI: http://orca.cf.ac.uk/id/eprint/22836

Citation Data

Cited 13 times in Google Scholar. View in Google Scholar

Cited 28 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item

Downloads

Downloads per month over past year

View more statistics