Dictamnine derivatives as a novel family of dual inhibitors for cholinesterase and -amyloid aggregation
JOURNAL OF MOLECULAR STRUCTURE(2023)
Abstract
A novel series of dictamnine derivatives were synthesized and evaluated as dual inhibitors for cholinesterase and beta-amyloid aggregation. These molecules exhibited potent acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities at the micromolar to sub-micromolar levels. Compound 7k exhibited the strongest inhibitory activity for both AChE and BChE, with IC50 values of 0.40 mu M and 0.63 mu M, respectively, improving results from its precursor dictamnine and the commercial inhibitor galanthamine. Kinetic analyses and molecular modeling results indicated a mixed-type inhibition of AChE by compound 7k. In addition, some of the derivatives revealed potent inhibitory activity of AChE induced beta-amyloid (A beta) aggregation. Moreover, 7k did not show toxicity against SH-SY5Y and HL-7702 cells at the tested concentration. Therefore, these dictamnine derivatives, and especially 7k, are suitable candidates for the treatment of Alzheimer's disease and should be further studied.
MoreTranslated text
Key words
Furoquinoline,Dictamnine,Cholinesterase,beta-amyloid,Alzheimer's disease
AI Read Science
Must-Reading Tree
Example
![](https://originalfileserver.aminer.cn/sys/aminer/pubs/mrt_preview.jpeg)
Generate MRT to find the research sequence of this paper
Chat Paper
Summary is being generated by the instructions you defined