Issue 21, 2025, Issue in Progress

Flavonoid carbamate hybrids: design, synthesis, and evaluation as multi-target enzyme inhibitors for Alzheimer's disease

Abstract

Alzheimer's disease is characterized by cholinergic dysfunction and neuroinflammation, with acetylcholinesterase and monoacylglycerol lipase emerging as important therapeutic targets. In this study, a series of novel flavonoid carbamate derivatives were synthesized from chrysin and kaempferol, and their structures were confirmed via NMR and HRMS spectroscopy. The inhibitory activities of these compounds were evaluated against acetylcholinesterase and monoacylglycerol lipase using in vitro enzymatic assays. Among them, C3 and C5 exhibited significant dual inhibition, with IC50 values of 22.86 μM and 46.65 μM for monoacylglycerol lipase, and 61.78 μM and 89.40 μM for acetylcholinesterase, respectively. Molecular docking studies revealed key binding interactions, while molecular dynamics simulations demonstrated their stability within the active sites of target enzymes. These findings highlight C3 and C5 as promising candidates for further investigation in the development of dual acetylcholinesterase/monoacylglycerol lipase inhibitors for Alzheimer's disease treatment.

Graphical abstract: Flavonoid carbamate hybrids: design, synthesis, and evaluation as multi-target enzyme inhibitors for Alzheimer's disease

Supplementary files

Article information

Article type
Paper
Submitted
01 Apr 2025
Accepted
14 May 2025
First published
20 May 2025
This article is Open Access
Creative Commons BY license

RSC Adv., 2025,15, 16855-16868

Flavonoid carbamate hybrids: design, synthesis, and evaluation as multi-target enzyme inhibitors for Alzheimer's disease

T. Tran, D. Doan, T. Cao, T. Tran and T. Tran, RSC Adv., 2025, 15, 16855 DOI: 10.1039/D5RA02267C

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements