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Design, synthesis and biological evaluation of dihydrofurocoumarin derivatives as potent neuraminidase inhibitors.
- Source :
-
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2021 Apr 01; Vol. 37, pp. 127839. Date of Electronic Publication: 2021 Feb 05. - Publication Year :
- 2021
-
Abstract
- Neuraminidase (NA) is a promising target for development of anti-influenza drugs. In this study a dihydrofurocoumarin derivative ZINC05577497 was discovered as a lead NA inhibitor based on docking-based virtual screening technique. The optimization of lead ZINC05577497 led to the discovery of a series of novel NA inhibitors 5a-5j. Compound 5b has the most potent activity against NA with IC <subscript>50</subscript>  = 0.02 µM, which is lower than those of the reference oseltamivir carboxylate (OSC) (IC <subscript>50</subscript>  = 0.04 µM) and ZINC05577497 (IC <subscript>50</subscript>  = 0.11 µM). Other target compounds also show potential inhibition of NA activity. Molecular docking results indicate that the good potency of 5b may be attributed to the elongation of the dihydrofurocoumarin ring to the 150-cavity. The results of this paper will be useful to discover more potent NA inhibitors.<br /> (Copyright © 2021 Elsevier Ltd. All rights reserved.)
- Subjects :
- Dose-Response Relationship, Drug
Enzyme Inhibitors chemical synthesis
Enzyme Inhibitors chemistry
Furocoumarins chemical synthesis
Furocoumarins chemistry
Humans
Molecular Dynamics Simulation
Molecular Structure
Neuraminidase metabolism
Structure-Activity Relationship
Drug Design
Enzyme Inhibitors pharmacology
Furocoumarins pharmacology
Neuraminidase antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1464-3405
- Volume :
- 37
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry letters
- Publication Type :
- Academic Journal
- Accession number :
- 33556571
- Full Text :
- https://doi.org/10.1016/j.bmcl.2021.127839