1. Benzothiazole-Propanamide Linker Pyrrolidine (Morpholine) as Monoamine Oxidase-B and Butyrylcholinesterase Inhibitors.
- Author
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He ZW, Jiang BSK, Sun XH, Tang M, Liu YW, Guan LP, and Wu D
- Subjects
- Humans, Monoamine Oxidase Inhibitors pharmacology, Acetylcholinesterase metabolism, Cholinesterase Inhibitors chemistry, Monoamine Oxidase, Benzothiazoles pharmacology, Morpholines, Structure-Activity Relationship, Molecular Structure, Molecular Docking Simulation, Butyrylcholinesterase metabolism, Alzheimer Disease
- Abstract
According to the fusion technique create effective multi-target-directed ligands, in this study, we designed and synthesized a series of benzo[d]thiazol-2-yl)-3-(pyrrolidin-1-yl) or 3-(morph- olino-1-yl)propanamide derivatives, and evaluated their inhibitory potency against MAOs, AChE, BuChE by in vitro enzyme effect assays. Based on activity results, we found that derivatives N-(5-methylbenzo[d]thiazol-2-yl)-3-(pyrrolidin-1-yl)propanamide (2 c) and N-(6-bromobenzo[d]thiazol-2-yl)-3-(pyrrolidin-1-yl)propanamide (2 h) showed good inhibitory potency against BuChE with IC
50 values of 15.12 μM and 12.33 μM, respectively. Besides, 2 c and 2 h also exhibited selective MAO-B inhibitory effects with inhibition rates of 60.10 % and 66.30 % at 100 μM, respectively. In contrast, all designed derivatives were poor active against AChE and MAO-A at a concentration of 100 μM. The toxicity analysis in vitro by MTT and AO/EB fluorescence staining confirmed that 2 c and 2 h were nontoxic up to 100 μM. Molecular modeling studies showed that 2 c and 2 h could bind to the active site of BuChE. This research paves the way for further study aimed at designing MAO-B and BuChE inhibitors for the treatment of neurodegenerative disorders., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)- Published
- 2023
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