The final stages of polio eradication are proving more difficult than the early phases and the development of effective drugs and treatments is considered a priority, thus the research is ongoing. A screening of our in-house chemical library against poliovirus Sabin strains led to identification of 5 and 6 as hits active at submicromolar concentration. Derivatives of these compounds were synthesized as a preliminary structure-activity relationship study. Among them, 7 and 11 were highly active against poliovirus Sabin 1, 2 and 3. 11 was also very potent against a large panel of wild and vaccine-derived polioviruses. Time of addition experiments suggest that 5 and 7 could be active at an early stage of viral replication, while 11 was active at same concentration at all stages of viral replication. A ligand-based approach was applied to find the common structural features shared by the new compounds and already known poliovirus inhibitors.

In vitro antiviral activity of new oxazoline derivatives as potent poliovirus inhibitors / Madia, Valentina Noemi; Messore, Antonella; Pescatori, Luca; Saccoliti, Francesco; Tudino, Valeria; De Leo, Alessandro; Scipione, Luigi; Fiore, Lucia; Rhoden, Eric; Manetti, Fabrizio; Oberste, M Steven; Di Santo, Roberto; Costi, Roberta. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - 62:(2019), pp. 798-810. [10.1021/acs.jmedchem.8b01482]

In vitro antiviral activity of new oxazoline derivatives as potent poliovirus inhibitors

Madia, Valentina Noemi;Messore, Antonella;Pescatori, Luca;Saccoliti, Francesco;Tudino, Valeria;De Leo, Alessandro;Scipione, Luigi;Di Santo, Roberto
Penultimo
;
Costi, Roberta
Ultimo
2019

Abstract

The final stages of polio eradication are proving more difficult than the early phases and the development of effective drugs and treatments is considered a priority, thus the research is ongoing. A screening of our in-house chemical library against poliovirus Sabin strains led to identification of 5 and 6 as hits active at submicromolar concentration. Derivatives of these compounds were synthesized as a preliminary structure-activity relationship study. Among them, 7 and 11 were highly active against poliovirus Sabin 1, 2 and 3. 11 was also very potent against a large panel of wild and vaccine-derived polioviruses. Time of addition experiments suggest that 5 and 7 could be active at an early stage of viral replication, while 11 was active at same concentration at all stages of viral replication. A ligand-based approach was applied to find the common structural features shared by the new compounds and already known poliovirus inhibitors.
2019
poliomyelitis; poliovirus; antivirals; oxazoline; vaccine-derived polioviruses
01 Pubblicazione su rivista::01a Articolo in rivista
In vitro antiviral activity of new oxazoline derivatives as potent poliovirus inhibitors / Madia, Valentina Noemi; Messore, Antonella; Pescatori, Luca; Saccoliti, Francesco; Tudino, Valeria; De Leo, Alessandro; Scipione, Luigi; Fiore, Lucia; Rhoden, Eric; Manetti, Fabrizio; Oberste, M Steven; Di Santo, Roberto; Costi, Roberta. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - 62:(2019), pp. 798-810. [10.1021/acs.jmedchem.8b01482]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1205976
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