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, 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

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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:	26 Sep 2018 05:19
URI:	http://orca.cf.ac.uk/id/eprint/115209

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