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In Vitro Antiviral Activity of New Oxazoline Derivatives as Potent Poliovirus Inhibitors.
- Source :
-
Journal of medicinal chemistry [J Med Chem] 2019 Jan 24; Vol. 62 (2), pp. 798-810. Date of Electronic Publication: 2018 Dec 18. - Publication Year :
- 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 the identification of compounds 5 and 6 as hits active at submicromolar concentrations. Derivatives of these compounds were synthesized as a preliminary structure-activity-relationship study. Among them, 7 and 11 were highly active against poliovirus Sabin 1-3. Compound 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, whereas 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.
- Subjects :
- Antiviral Agents chemical synthesis
Antiviral Agents pharmacology
Binding Sites
HeLa Cells
Humans
Molecular Dynamics Simulation
Oxazoles chemical synthesis
Oxazoles pharmacology
Poliovirus chemistry
Structure-Activity Relationship
Virus Replication drug effects
Antiviral Agents chemistry
Oxazoles chemistry
Poliovirus physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1520-4804
- Volume :
- 62
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Journal of medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 30512950
- Full Text :
- https://doi.org/10.1021/acs.jmedchem.8b01482