Anti-influenza A virus activity and structure–activity relationship of a series of nitrobenzoxadiazole derivatives
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 pathway...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2021-01-01
|
| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/14756366.2021.1982932 |
| _version_ | 1818332546660827136 |
|---|---|
| author | Francesco Fiorentino Marta De Angelis Martina Menna Annarita Rovere Anna Maria Caccuri Francesca D’Acunzo Anna Teresa Palamara Lucia Nencioni Dante Rotili Antonello Mai |
| author_facet | Francesco Fiorentino Marta De Angelis Martina Menna Annarita Rovere Anna Maria Caccuri Francesca D’Acunzo Anna Teresa Palamara Lucia Nencioni Dante Rotili Antonello Mai |
| author_sort | Francesco Fiorentino |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T13:37:28Z |
| format | Article |
| id | doaj.art-ecff4c5a42794137b561ff775ca35eb0 |
| institution | Directory Open Access Journal |
| issn | 1475-6366 1475-6374 |
| language | English |
| last_indexed | 2024-12-13T13:37:28Z |
| publishDate | 2021-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj.art-ecff4c5a42794137b561ff775ca35eb02022-12-21T23:43:44ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742021-01-013612128213810.1080/14756366.2021.19829321982932Anti-influenza A virus activity and structure–activity relationship of a series of nitrobenzoxadiazole derivativesFrancesco Fiorentino0Marta De Angelis1Martina Menna2Annarita Rovere3Anna Maria Caccuri4Francesca D’Acunzo5Anna Teresa Palamara6Lucia Nencioni7Dante Rotili8Antonello Mai9Department of Drug Chemistry and Technologies, Sapienza University of RomeDepartment of Public Health and Infectious Diseases, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of RomeDepartment of Drug Chemistry and Technologies, Sapienza University of RomeDepartment of Drug Chemistry and Technologies, Sapienza University of RomeDepartment of Chemical Sciences and Technologies, University of Rome Tor VergataCNR, Istituto di Metodologie Chimiche, Sezione Meccanismi di Reazione, Sapienza University of RomeDepartment of Public Health and Infectious Diseases, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of RomeDepartment of Public Health and Infectious Diseases, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of RomeDepartment of Drug Chemistry and Technologies, Sapienza University of RomeDepartment of Drug Chemistry and Technologies, Sapienza University of RomeInfluenza 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.http://dx.doi.org/10.1080/14756366.2021.1982932influenza a virusnitrobenzoxadiazolesrna polymerase inhibitorsantivirals |
| spellingShingle | Francesco Fiorentino Marta De Angelis Martina Menna Annarita Rovere Anna Maria Caccuri Francesca D’Acunzo Anna Teresa Palamara Lucia Nencioni Dante Rotili Antonello Mai Anti-influenza A virus activity and structure–activity relationship of a series of nitrobenzoxadiazole derivatives Journal of Enzyme Inhibition and Medicinal Chemistry influenza a virus nitrobenzoxadiazoles rna polymerase inhibitors antivirals |
| title | Anti-influenza A virus activity and structure–activity relationship of a series of nitrobenzoxadiazole derivatives |
| title_full | Anti-influenza A virus activity and structure–activity relationship of a series of nitrobenzoxadiazole derivatives |
| title_fullStr | Anti-influenza A virus activity and structure–activity relationship of a series of nitrobenzoxadiazole derivatives |
| title_full_unstemmed | Anti-influenza A virus activity and structure–activity relationship of a series of nitrobenzoxadiazole derivatives |
| title_short | Anti-influenza A virus activity and structure–activity relationship of a series of nitrobenzoxadiazole derivatives |
| title_sort | anti influenza a virus activity and structure activity relationship of a series of nitrobenzoxadiazole derivatives |
| topic | influenza a virus nitrobenzoxadiazoles rna polymerase inhibitors antivirals |
| url | http://dx.doi.org/10.1080/14756366.2021.1982932 |
| work_keys_str_mv | AT francescofiorentino antiinfluenzaavirusactivityandstructureactivityrelationshipofaseriesofnitrobenzoxadiazolederivatives AT martadeangelis antiinfluenzaavirusactivityandstructureactivityrelationshipofaseriesofnitrobenzoxadiazolederivatives AT martinamenna antiinfluenzaavirusactivityandstructureactivityrelationshipofaseriesofnitrobenzoxadiazolederivatives AT annaritarovere antiinfluenzaavirusactivityandstructureactivityrelationshipofaseriesofnitrobenzoxadiazolederivatives AT annamariacaccuri antiinfluenzaavirusactivityandstructureactivityrelationshipofaseriesofnitrobenzoxadiazolederivatives AT francescadacunzo antiinfluenzaavirusactivityandstructureactivityrelationshipofaseriesofnitrobenzoxadiazolederivatives AT annateresapalamara antiinfluenzaavirusactivityandstructureactivityrelationshipofaseriesofnitrobenzoxadiazolederivatives AT lucianencioni antiinfluenzaavirusactivityandstructureactivityrelationshipofaseriesofnitrobenzoxadiazolederivatives AT danterotili antiinfluenzaavirusactivityandstructureactivityrelationshipofaseriesofnitrobenzoxadiazolederivatives AT antonellomai antiinfluenzaavirusactivityandstructureactivityrelationshipofaseriesofnitrobenzoxadiazolederivatives |