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

Journal of Enzyme Inhibition and Medicinal Chemistry

Francesca D’Acunzo¹  Anna Maria Caccuri²  Antonello Mai³  Dante Rotili³  Francesco Fiorentino³  Martina Menna³  Annarita Rovere³  Lucia Nencioni⁴  Marta De Angelis⁴  Anna Teresa Palamara⁵ 

[1] CNR, Istituto di Metodologie Chimiche, Sezione Meccanismi di Reazione, Sapienza University of Rome, Rome, Ital;Department of Chemical Sciences and Technologies, University of Rome Tor Vergata, Rome, Ital;Department of Drug Chemistry and Technologies, Sapienza University of Rome, Rome, Ital;Department of Public Health and Infectious Diseases, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome, Rome, Ital;Department of Public Health and Infectious Diseases, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome, Rome, Ital;Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Ital;

关键词: Influenza A virus;    nitrobenzoxadiazoles;    RNA polymerase inhibitors;    antivirals;   

DOI  :  10.1080/14756366.2021.1982932

来源: Taylor & Francis

【 摘 要 】

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.

【 授权许可】

CC BY