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: | 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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