Benzothiazole-Propanamide Linker Pyrrolidine (Morpholine) as Monoamine Oxidase-B and Butyrylcholinesterase Inhibitors.
Chem Biodivers
; 20(12): e202301271, 2023 Dec.
Article
em En
| MEDLINE
| ID: mdl-37806964
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 inâ
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 IC50 values of 15.12â
µM and 12.33â
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 100â
µM, respectively. In contrast, all designed derivatives were poor active against AChE and MAO-A at a concentration of 100â
µM. The toxicity analysis inâ
vitro by MTT and AO/EB fluorescence staining confirmed that 2 c and 2 h were nontoxic up to 100â
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Butirilcolinesterase
/
Doença de Alzheimer
Limite:
Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article