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New Disulfiram Derivatives as MAGL-Selective Inhibitors.
- Source :
-
Molecules (Basel, Switzerland) [Molecules] 2021 May 30; Vol. 26 (11). Date of Electronic Publication: 2021 May 30. - Publication Year :
- 2021
-
Abstract
- Monoacylglycerol lipase (MAGL) is a key enzyme in the human endocannabinoid system. It is also the main enzyme responsible for the conversion of 2-arachidonoyl glycerol (2-AG) to arachidonic acid (AA), a precursor of prostaglandin synthesis. The inhibition of MAGL activity would be beneficial for the treatment of a wide range of diseases, such as inflammation, neurodegeneration, metabolic disorders and cancer. Here, the author reports the pharmacological evaluation of new disulfiram derivatives as potent inhibitors of MAGL. These analogues displayed high inhibition selectivity over fatty acid amide hydrolase (FAAH), another endocannabinoid-hydrolyzing enzyme. In particular, compound 2i inhibited MAGL in the low micromolar range. However, it did not show any inhibitory activity against FAAH.
- Subjects :
- Amidohydrolases chemistry
Arachidonic Acids chemistry
Carbamates pharmacology
Disulfiram analogs & derivatives
Endocannabinoids chemistry
Endocannabinoids metabolism
Enzyme Inhibitors pharmacology
Glycerides chemistry
Humans
Hydrolysis
Monoglycerides chemistry
Structure-Activity Relationship
Disulfiram pharmacology
Monoacylglycerol Lipases antagonists & inhibitors
Monoacylglycerol Lipases chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1420-3049
- Volume :
- 26
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Molecules (Basel, Switzerland)
- Publication Type :
- Academic Journal
- Accession number :
- 34070869
- Full Text :
- https://doi.org/10.3390/molecules26113296