Castelli, Riccardo published the artcileBenzisothiazolinone Derivatives as Potent Allosteric Monoacylglycerol Lipase Inhibitors That Functionally Mimic Sulfenylation of Regulatory Cysteines, Safety of 2,2′-Dithiodibenzoic acid, the publication is Journal of Medicinal Chemistry (2020), 63(3), 1261-1280, database is CAplus and MEDLINE.
We describe a set of benzisothiazolinone (BTZ) derivatives that are potent inhibitors of monoacylglycerol lipase (MGL), the primary degrading enzyme for the endocannabinoid 2-arachidonoyl-sn-glycerol (2-AG). Structure-activity relationship studies evaluated various substitutions on the nitrogen atom and the benzene ring of the BTZ nucleus. Optimized derivatives with nanomolar potency allowed to investigate the mechanism of MGL inhibition. Site-directed mutagenesis and mass spectrometry experiments showed that BTZs interact in a covalent reversible manner with regulatory cysteines, Cys201 and Cys208, causing a reversible sulfenylation known to modulate MGL activity. Metadynamics simulations revealed that BTZ adducts favor a closed conformation of MGL that occludes substrate recruitment. The BTZ derivative 13 protected neuronal cells from oxidative stimuli and increased 2-AG levels in mouse brain. The results identify Cys201 and Cys208 as key regulators of MGL function, and point to the BTZ scaffold as a useful starting point for the discovery of allosteric MGL inhibitors.
Journal of Medicinal Chemistry published new progress about 119-80-2. 119-80-2 belongs to catalysis-chemistry, auxiliary class sulfides,Carboxylic acid,Benzene, name is 2,2′-Dithiodibenzoic acid, and the molecular formula is C14H10O4S2, Safety of 2,2′-Dithiodibenzoic acid.
Referemce:
https://courses.lumenlearning.com/boundless-chemistry/chapter/catalysis/,
Catalysis – Wikipedia