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 ORCID: https://orcid.org/0000-0003-3227-1537, 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

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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:	26 Nov 2024 18:15
URI:	https://orca.cardiff.ac.uk/id/eprint/115115

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