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

Exploring the cycloheptathiophene-3-carboxamide scaffold to disrupt the interactions of the influenza polymerase subunits and obtain potent anti-influenza activity

Desantis, Jenny, Nannetti, Giulio ORCID: https://orcid.org/0000-0003-3227-1537, Massari, Serena, Barreca, Maria Letizia, Manfroni, Giuseppe, Cecchetti, Violetta, Palù, Giorgio, Goracci, Laura, Loregian, Arianna and Tabarrini, Oriana 2017. Exploring the cycloheptathiophene-3-carboxamide scaffold to disrupt the interactions of the influenza polymerase subunits and obtain potent anti-influenza activity. European Journal of Medicinal Chemistry 138 , pp. 128-139. 10.1016/j.ejmech.2017.06.015

[thumbnail of Exploring the cycloheptathiophene-3-carboxamide scaffold to disrupt the interactions of the influenza polymerase subunits and obtain potent anti-influenza activity.pdf]
Preview
PDF - Accepted Post-Print Version
Download (902kB) | Preview

Abstract

With the aim to identify small molecules able to disrupt PA-PB1 subunits interaction of influenza virus (flu) RNA-dependent RNA polymerase, and based on previous structural and computational information, in this paper we have designed and synthesized a new series of cycloheptathiophene-3-carboxamide (cHTC) derivatives. Their biological evaluation led to highlight important structural insights along with new interesting compounds, such as the 2-hydroxybenzamido derivatives 29, 31, and 32, and the 4-aminophenyl derivative 54, which inhibited viral growth in the low micromolar range (EC50 = 0.18–1.2 μM) at no toxic concentrations (CC50 > 250 μM). This study permitted to obtain among the most potent anti-flu compounds within the PA-PB1 interaction inhibitors, confirming the cHTC scaffold as particularly suitable to achieve innovative anti-flu agents.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Pharmacy
Publisher: Elsevier
ISSN: 0223-5234
Date of First Compliant Deposit: 24 September 2018
Date of Acceptance: 7 June 2017
Last Modified: 08 Nov 2023 12:40
URI: https://orca.cardiff.ac.uk/id/eprint/115209

Citation Data

Cited 35 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