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.
|Titolo:||In vitro Antiviral Activity of New Oxazoline Derivatives as Potent Poliovirus Inhibitors|
MANETTI, FABRIZIO [Conceptualization]
|Citazione:||Madia, V.N., Messore, A., Pescatori, L., Saccoliti, F., Tudino, V., De Leo, A., et al. (2019). In vitro Antiviral Activity of New Oxazoline Derivatives as Potent Poliovirus Inhibitors. JOURNAL OF MEDICINAL CHEMISTRY, 62(2), 798-810.|
|Appare nelle tipologie:||1.1 Articolo in rivista|