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Anti-influenza A virus activity and structure-activity relationship of a series of nitrobenzoxadiazole derivatives.

Francesco FiorentinoMarta De AngelisMartina MennaAnnarita RovereAnna Maria CaccuriFrancesca D'AcunzoAnna Teresa PalamaraLucia NencioniDante RotiliAntonello Mai
Published in: Journal of enzyme inhibition and medicinal chemistry (2022)
Influenza viruses represent a major threat to human health and are responsible for seasonal epidemics, along with pandemics. Currently, few therapeutic options are available, with most drugs being at risk of the insurgence of resistant strains. Hence, novel approaches targeting less explored pathways are urgently needed. In this work, we assayed a library of nitrobenzoxadiazole derivatives against the influenza virus A/Puerto Rico/8/34 H1N1 (PR8) strain. We identified three promising 4-thioether substituted nitrobenzoxadiazoles ( 12 , 17 , and 25 ) that were able to inhibit viral replication at low micromolar concentrations in two different infected cell lines using a haemagglutination assay. We further assessed these molecules using an In-Cell Western assay, which confirmed their potency in the low micromolar range. Among the three molecules, 12 and 25 displayed the most favourable profile of activity and selectivity and were selected as hit compounds for future optimisation studies.
Keyphrases
  • structure activity relationship
  • human health
  • risk assessment
  • high throughput
  • escherichia coli
  • climate change
  • single cell
  • sars cov
  • cell therapy
  • south africa
  • cancer therapy
  • genetic diversity