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

Synthesis and biological evaluation of a library of hybrid derivatives as inhibitors of influenza virus PA-PB1 interaction

D'Agostino, Ilaria, Giacchello, Ilaria, Nannetti, Giulio, Fallacara, Anna Lucia, Deodato, Davide, Musumeci, Francesca, Grossi, Giancarlo, Palù, Giorgio, Cau, Ylenia, Trist, Iuni Margaret, Loregian, Arianna, Schenone, Silvia and Botta, Maurizio 2018. Synthesis and biological evaluation of a library of hybrid derivatives as inhibitors of influenza virus PA-PB1 interaction. European Journal of Medicinal Chemistry 157 , pp. 743-758. 10.1016/j.ejmech.2018.08.032
Item availability restricted.

[img] PDF - Accepted Post-Print Version
Restricted to Repository staff only until 13 August 2019 due to copyright restrictions.

Download (998kB)

Abstract

The limited treatment options against influenza virus along with the growing public health concerns regarding the continuous emergence of drug-resistant viruses make essential the development of new anti-flu agents with novel mechanisms of action. One of the most attractive targets is the interaction between two subunits of the RNA-dependent RNA polymerase, PA and PB1. Herein we report the rational design of hybrid compounds starting from a 3-cyano-4,6-diphenylpyridine scaffold recently identified as disruptor of PA-PB1 interactions. Guided by the previously reported SAR data, a library of amino acid derivatives was synthesized. The biological evaluation led to the identification of new PA-PB1 inhibitors, that do not show appreciable toxicity. Molecular modeling shed further lights on the inhibition mechanism of these compounds.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Pharmacy
Publisher: Elsevier
ISSN: 0223-5234
Date of First Compliant Deposit: 20 September 2018
Date of Acceptance: 11 August 2018
Last Modified: 22 Sep 2018 07:39
URI: http://orca.cf.ac.uk/id/eprint/115115

Citation Data

Cited 2 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