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

European Journal of Medicinal Chemistry
Ilaria D'AgostinoMaurizio Botta

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.

Citations

Apr 26, 2019·Expert Opinion on Investigational Drugs·Jie YangShuwen Liu
Oct 6, 2020·Expert Opinion on Therapeutic Patents·Tiziana Ginex, F Javier Luque
Oct 13, 2020·ACS Infectious Diseases·Serena MassariOriana Tabarrini
Dec 6, 2019·Journal of Chemical Information and Modeling·Mattia MoriAndrea Tafi

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