title: 4-Aryliden-2-methyloxazol-5(4H)-one as a new scaffold for selective reversible MAGL inhibitors.
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.
authors: a Department of Pharmacy , University of Pisa , Pisa , Italy and.
authors: Carlotta
authors: C
authors: Granchi
authors: b Sbarro Institute for Cancer Research and Molecular Medicine Center for Biotechnology, Temple University , Philadelphia , PA , USA.
authors: Flavio
authors: F
authors: Rizzolio
authors: a Department of Pharmacy , University of Pisa , Pisa , Italy and.
authors: Vittorio
authors: V
authors: Bordoni
authors: b Sbarro Institute for Cancer Research and Molecular Medicine Center for Biotechnology, Temple University , Philadelphia , PA , USA.
authors: Isabella
authors: I
authors: Caligiuri
authors: a Department of Pharmacy , University of Pisa , Pisa , Italy and.
authors: Clementina
authors: C
authors: Manera
authors: a Department of Pharmacy , University of Pisa , Pisa , Italy and.
authors: Marco
authors: M
authors: Macchia
authors: a Department of Pharmacy , University of Pisa , Pisa , Italy and.
authors: Filippo
authors: F
authors: Minutolo
authors: a Department of Pharmacy , University of Pisa , Pisa , Italy and.
authors: Adriano
authors: A
authors: Martinelli
authors: b Sbarro Institute for Cancer Research and Molecular Medicine Center for Biotechnology, Temple University , Philadelphia , PA , USA.
authors: Antonio
authors: A
authors: Giordano
authors: a Department of Pharmacy , University of Pisa , Pisa , Italy and.|b Sbarro Institute for Cancer Research and Molecular Medicine Center for Biotechnology, Temple University , Philadelphia , PA , USA.
authors: Tiziano
authors: T
authors: Tuccinardi
mesh_terms: D000581:Amidohydrolases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D008994:Monoacylglycerol Lipases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010081:Oxazolone / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D008994:Monoacylglycerol Lipases; D010081:Oxazolone; D000099252:Fatty Acid Amide Hydrolases
keywords: Hydrolase; MAGL; MAGL inhibitors; monoacylglycerol lipase; monoacylglycerol lipase inhibitors