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

Structural investigation of Cycloheptathiophene-3-carboxamide derivatives targeting influenza virus polymerase assembly

Massari, Serena, Nannetti, Giulio, Goracci, Laura, Sancineto, Luca, Muratore, Giulia, Sabatini, Stefano, Manfroni, Giuseppe, Mercorelli, Beatrice, Cecchetti, Violetta, Facchini, Marzia, Palù, Giorgio, Cruciani, Gabriele, Loregian, Arianna and Tabarrini, Oriana 2013. Structural investigation of Cycloheptathiophene-3-carboxamide derivatives targeting influenza virus polymerase assembly. Journal of Medicinal Chemistry 56 (24) , pp. 10118-10131. 10.1021/jm401560v

[img]
Preview
PDF - Accepted Post-Print Version
Download (1MB) | Preview

Abstract

The limited number of drug classes licensed for treatment of influenza virus (Flu), together with the continuous emergence of viral variants and drug resistant mutants, highlights the urgent need to find antivirals with novel mechanisms of action. In this context, the viral RNA-dependent RNA polymerase (RdRP) subunits assembly has emerged as an attractive target. Starting from a cycloheptathiophene-3-carboxamide derivative recently identified by us for its ability to disrupt the interaction between the PA and PB1 subunits of RdRP, we have designed and synthesized a series of analogues. Their biological evaluation led to the identification of more potent protein–protein interaction inhibitors, endowed with antiviral activity that also encompassed a number of clinical isolates of FluA, including an oseltamivir-resistant strain, and FluB, without showing appreciable toxicity. From this study, the cycloheptathiophene-3-carboxamide scaffold emerged as being particularly suitable to impart anti-Flu activity.

Item Type: Article
Date Type: Published Online
Status: Published
Schools: Pharmacy
Publisher: American Chemical Society
ISSN: 0022-2623
Date of First Compliant Deposit: 24 September 2018
Date of Acceptance: 7 October 2013
Last Modified: 20 Oct 2018 07:48
URI: http://orca.cf.ac.uk/id/eprint/115203

Citation Data

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