Abstract
This study reports on a preliminary structure-activity relationship exploration of 4-aryliden-2-methyloxazol-5(4H)-one-based compounds as MAGL/FAAH inhibitors. Our results highlight that this scaffold may serve for the development of selective MAGL inhibitors. A 69-fold selectivity against MAGL over FAAH was achieved for compound 16b (MAGL and FAAH IC(50) = 1.6 and 111 µM, respectively). Furthermore, the best compound behaved as a reversible ligand and showed promising antiproliferative activity in cancer cells.
Keywords:
Hydrolase; MAGL; MAGL inhibitors; monoacylglycerol lipase; monoacylglycerol lipase inhibitors.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amidohydrolases / antagonists & inhibitors
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Amidohydrolases / metabolism
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Antineoplastic Agents / chemical synthesis
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology*
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Cell Survival / drug effects
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Dose-Response Relationship, Drug
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Drug Screening Assays, Antitumor
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology*
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Humans
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Molecular Docking Simulation
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Molecular Structure
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Monoacylglycerol Lipases / antagonists & inhibitors*
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Monoacylglycerol Lipases / metabolism
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Oxazolone / chemical synthesis
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Oxazolone / chemistry
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Oxazolone / pharmacology*
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Structure-Activity Relationship
Substances
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Antineoplastic Agents
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Enzyme Inhibitors
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Oxazolone
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Monoacylglycerol Lipases
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Amidohydrolases
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fatty-acid amide hydrolase