Literature DB >> 24900454

The First Dual ChE/FAAH Inhibitors: New Perspectives for Alzheimer's Disease?

Angela Rampa1, Manuela Bartolini1, Alessandra Bisi1, Federica Belluti1, Silvia Gobbi1, Vincenza Andrisano1, Alessia Ligresti2, Vincenzo Di Marzo2.   

Abstract

The treatment of Alzheimer's disease (AD) still remains an area of significant unmet need, with drugs that only target the symptoms of the disease. Therefore, there is considerable need for disease-modifying therapies. The complex etiology of AD prompts scientists to develop multitarget strategies to combat causes and symptoms. To this aim, we designed, synthesized, and tested four new carbamates as dual cholinesterase-FAAH inhibitors. The dual activity of these compounds could lead to a potentially more effective treatment for the counteraction of AD progression, because they would allow regulation of both ACh and eCB signaling and improve neuronal transmission and/or counteract neuroinflammation.

Entities:  

Keywords:  AChE; Alzheimer's disease; BuChE; FAAH; carbamate inhibitors; drug design

Year:  2012        PMID: 24900454      PMCID: PMC4025825          DOI: 10.1021/ml200313p

Source DB:  PubMed          Journal:  ACS Med Chem Lett        ISSN: 1948-5875            Impact factor:   4.345


  29 in total

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4.  Selective butyrylcholinesterase inhibition elevates brain acetylcholine, augments learning and lowers Alzheimer beta-amyloid peptide in rodent.

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Journal:  Proc Natl Acad Sci U S A       Date:  2005-11-07       Impact factor: 11.205

5.  Anandamide and its congeners inhibit human plasma butyrylcholinesterase. Possible new roles for these endocannabinoids?

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Review 7.  Cholinergic function and Alzheimer's disease.

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Journal:  Int J Geriatr Psychiatry       Date:  2003-09       Impact factor: 3.485

Review 8.  Overview of the chemical families of fatty acid amide hydrolase and monoacylglycerol lipase inhibitors.

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Review 10.  The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics.

Authors:  John Hardy; Dennis J Selkoe
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  6 in total

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2.  Aryl N-[ω-(6-Fluoroindol-1-yl)alkyl]carbamates as Inhibitors of Fatty Acid Amide Hydrolase, Monoacylglycerol Lipase, and Butyrylcholinesterase: Structure-Activity Relationships and Hydrolytic Stability.

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Journal:  ACS Omega       Date:  2021-05-14

3.  Combining Chalcones with Donepezil to Inhibit Both Cholinesterases and Aβ Fibril Assembly.

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Review 4.  Polypharmacological Approaches for CNS Diseases: Focus on Endocannabinoid Degradation Inhibition.

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5.  New Coumarin Derivatives as Cholinergic and Cannabinoid System Modulators.

Authors:  Serena Montanari; Marco Allarà; Laura Scalvini; Magdalena Kostrzewa; Federica Belluti; Silvia Gobbi; Marina Naldi; Silvia Rivara; Manuela Bartolini; Alessia Ligresti; Alessandra Bisi; Angela Rampa
Journal:  Molecules       Date:  2021-05-28       Impact factor: 4.411

6.  Synthesis and Initial Characterization of a Selective, Pseudo-irreversible Inhibitor of Human Butyrylcholinesterase as PET Tracer.

Authors:  Christian Gentzsch; Matthias Hoffmann; Yasuhiro Ohshima; Naoko Nose; Xinyu Chen; Takahiro Higuchi; Michael Decker
Journal:  ChemMedChem       Date:  2021-03-01       Impact factor: 3.466

  6 in total

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