Chinese Journal of Organic Chemistry >
Design, Synthesis and Biological Activity Studies of 2-(1,3-Dioxoiso-indolin-2-yl)-N-phenethylacetamide and 2-(3,4-Dihydroisoquinolin-1-yl)isoindole-1,3-dione as Monoamine Oxidase (MAO) and Cholinesterase (ChE) Inhibitors
Received date: 2023-11-24
Revised date: 2024-01-22
Online published: 2024-03-13
Supported by
Fujian Provincial Key Laboratory of Innovative Drug Target Research(FJ-YW-2023KF04); National College Student Innovation and Entrepreneurship Training Program(202310340048)
A series of 2-(1,3-dioxoisoindolin-2-yl)-N-phenethylacetamide and 2-(3,4-dihydroisoquinolin-1-yl)isoindole- 1,3-dione derivatives were synthesized and their biological activities of monoamine oxidase (MAO) and cholinesterase (ChE) inhibition were evaluated. The experimental results showed that all compounds exhibited certain inhibitory activity against MAOs. Upon separate monoamine oxidase A (MAO-A) and monoamine oxidase A (MAO-B) activity were studied, the compounds displayed better inhibition activity against MAO-B and weaker inhibition activity against MAO-A. Among these, 2-(1,3-dioxoisoindolin-2-yl)-N-(4-fluorophenethyl)acetamide (2h) and 2-((7-methoxy-3,4-dihydroisoquinolin-1-yl)methyl)iso- indoline-1,3-dione (3d) exhibited the most significant inhibition of MAO-A and MAO-B, with IC50 values of (3.87±0.59) and (3.35±0.53) μmol/L towards MAO, respectively. Results from cytotoxicity assays indicated that compounds with good inhi-bitory activity showed no cytotoxicity against L929 cells. Molecular docking of compounds 2h and 3d revealed significant interactions between the active analogs and amino acid residues of the protein receptors. Additionally, all compounds exhibited relatively weak inhibition activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE).
Yiming Hu , Jiayu Xu , Min Tang , Yawen Liu , Liping Guan , Qinghao Jin . Design, Synthesis and Biological Activity Studies of 2-(1,3-Dioxoiso-indolin-2-yl)-N-phenethylacetamide and 2-(3,4-Dihydroisoquinolin-1-yl)isoindole-1,3-dione as Monoamine Oxidase (MAO) and Cholinesterase (ChE) Inhibitors[J]. Chinese Journal of Organic Chemistry, 2024 , 44(6) : 1907 -1919 . DOI: 10.6023/cjoc202311027
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