Design and synthesis of new 1,2,3-triazole-methoxyphenyl-1,3,4-oxadiazole derivatives: selective butyrylcholinesterase inhibitors against Alzheimer’s disease

BMC Chemistry, Journal Year: 2025, Volume and Issue: 19(1)

Published: April 15, 2025

Alzheimer's disease (AD) remains a significant public health challenge due to its progressive cognitive impairment and the absence of proven treatments. In this study, several novel 1,2,3-triazole-methoxyphenyl-1,3,4-oxadiazole derivatives were synthesized evaluated for their ability inhibit key enzymes associated with AD: acetylcholinesterase (AChE) butyrylcholinesterase (BChE). Structure-activity relationship (SAR) analysis revealed that featuring electron-withdrawing groups, particularly nitro fluorine substituents, exhibited remarkable inhibitory activity against BChE while showing minimal effectiveness AChE. Among these, compound 13s (R = 4-CH3, R' 4-NO2) demonstrated highest potency, selectively targeting an IC50 value 11.01 µM. Molecular docking molecular dynamics (MD) simulations provided deeper insights into favorable interactions between these compounds BChE. Additionally, cytotoxicity studies confirmed active compound's limited toxicity toward normal cells, indicating promising therapeutic profile. These findings suggest selective anti-BChE hold potential consideration in later stages AD treatment.

Language: Английский

Isoindolinedione-Benzamide Pyridinium Derivatives for Targeting Alzheimer’s Disease

ACS Omega, Journal Year: 2024, Volume and Issue: 9(49), P. 48032 - 48043

Published: Nov. 25, 2024

An Isoindolinedione-benzamide pyridinium derivatives were designed through a structure-based strategy and synthesized as novel multifunctional anti-Alzheimer agents. The inhibitory activities of all 17 against acetylcholinesterase butyrylcholinesterase evaluated. Results exhibited that compound

Language: Английский