Journal article
Discovery of long-chain salicylketoxime derivatives as monoacylglycerol lipase (MAGL) inhibitors.
- Bononi G Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126, Pisa, Italy.
- Granchi C Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126, Pisa, Italy. Electronic address: carlotta.granchi@unipi.it.
- Lapillo M Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126, Pisa, Italy.
- Giannotti M Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126, Pisa, Italy.
- Nieri D Institute of Biochemistry and Molecular Medicine, NCCR TransCure, University of Bern, CH-3012, Bern, Switzerland.
- Fortunato S Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126, Pisa, Italy.
- Boustani ME Pathology Unit, Department of Molecular Biology and Translational Research, National Cancer Institute and Center for Molecular Biomedicine, Aviano (PN), Italy; Doctoral School in Molecular Biomedicine, University of Trieste, 34100, Trieste, Italy.
- Caligiuri I Pathology Unit, Department of Molecular Biology and Translational Research, National Cancer Institute and Center for Molecular Biomedicine, Aviano (PN), Italy.
- Poli G Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126, Pisa, Italy.
- Carlson KE Department of Chemistry, University of Illinois at Urbana-Champaign, 600 S. Mathews Avenue, Urbana, IL, 61801, USA.
- Kim SH Department of Chemistry, University of Illinois at Urbana-Champaign, 600 S. Mathews Avenue, Urbana, IL, 61801, USA.
- Macchia M Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126, Pisa, Italy.
- Martinelli A Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126, Pisa, Italy.
- Rizzolio F Pathology Unit, Department of Molecular Biology and Translational Research, National Cancer Institute and Center for Molecular Biomedicine, Aviano (PN), Italy; Department of Molecular Sciences and Nanosystems, Ca' Foscari University, Venezia, 30123, Italy.
- Chicca A Institute of Biochemistry and Molecular Medicine, NCCR TransCure, University of Bern, CH-3012, Bern, Switzerland.
- Katzenellenbogen JA Department of Chemistry, University of Illinois at Urbana-Champaign, 600 S. Mathews Avenue, Urbana, IL, 61801, USA.
- Minutolo F Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126, Pisa, Italy.
- Tuccinardi T Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126, Pisa, Italy.
- 2018-08-26
Published in:
- European journal of medicinal chemistry. - 2018
Cancer
Ketoxime
MAGL
Monoacylglycerol lipase inhibitors
Antineoplastic Agents
Cell Line, Tumor
Cell Proliferation
Cell Survival
Dose-Response Relationship, Drug
Drug Discovery
Drug Screening Assays, Antitumor
Enzyme Inhibitors
Humans
Models, Molecular
Molecular Structure
Monoacylglycerol Lipases
Oximes
Structure-Activity Relationship
English
Monoacylglycerol lipase (MAGL) is the enzyme hydrolyzing the endocannabinoid 2-arachidonoylglycerol (2-AG) to free arachidonic acid and glycerol. Therefore, MAGL is implicated in many physiological processes involving the regulation of the endocannabinoid system and eicosanoid network. MAGL inhibition represents a potential therapeutic target for many diseases, including cancer. Nowadays, most MAGL inhibitors inhibit this enzyme by an irreversible mechanism of action, potentially leading to unwanted side effects from chronic treatment. Herein, we report the discovery of long-chain salicylketoxime derivatives as potent and reversible MAGL inhibitors. The compounds herein described are characterized by a good target selectivity for MAGL and by antiproliferative activities against a series of cancer cell lines. Finally, modeling studies suggest a reasonable hypothetical binding mode for this class of compounds.
- Language
-
- English
- Open access status
- closed
- Identifiers
-
- DOI 10.1016/j.ejmech.2018.08.038
- PMID 30144699
- Persistent URL
- https://sonar.ch/global/documents/173490
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