Abstract
3-Acetyl-2,5-diaryl-2,3-dihydro-1,3,4-oxadiazoles were designed, synthesized, and tested as inhibitors against human monoamine oxidase (MAO) A and B isoforms. Several compounds, obtained as racemates, were identified as selective MAO-B inhibitors. The enantiomers of some derivatives were separated by enantioselective HPLC and tested. The R-enantiomers always showed the highest activity. Docking study and molecular dynamic simulations demonstrated the putative binding mode. We conclude that these 1,3,4-oxadiazoles derivatives are promising reversible and selective MAO-B inhibitors.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Line
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Drug Design
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Humans
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Insecta / cytology
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Isoenzymes / antagonists & inhibitors
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Models, Molecular
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Monoamine Oxidase Inhibitors / chemical synthesis*
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Monoamine Oxidase Inhibitors / chemistry
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Monoamine Oxidase Inhibitors / pharmacology
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Oxadiazoles / chemical synthesis*
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Oxadiazoles / chemistry
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Oxadiazoles / pharmacology
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Protein Binding
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Recombinant Proteins / antagonists & inhibitors
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Stereoisomerism
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Structure-Activity Relationship
Substances
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Isoenzymes
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Monoamine Oxidase Inhibitors
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Oxadiazoles
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Recombinant Proteins