Novel oxoisoaporphine-based inhibitors of acetyl- and butyrylcholinesterase and acetylcholinesterase-induced beta-amyloid aggregation

Bioorganic & Medicinal Chemistry Letters
Huang TangHong Liang

Abstract

A series of novel oxoisoaporphine-based inhibitors (10-aminoalkylamino-1-azabenzanthrone Ar-NH(CH(2))(n)NR(1)R(2)) of acetylcholinesterase (AChE) has been designed, synthesized, and tested for their ability to inhibit AChE, butyrylcholinesterase (BChE) and AChE-induced β-amyloid (Aβ) aggregation. The synthetic compounds exhibited high AChE inhibitory activity with IC(50) values in the submicromolar range in most cases. Non-competitive binding mode was found for these derivatives by the graphical analysis of steady-state inhibition data. Moreover, all compounds exhibit significant inhibitory activity on AChE-induced Aβ aggregation with inhibitory potency from 54.5% to 93.5%. Finally, six out of twelve synthetic compounds were predicted to be able to cross the blood-brain barrier (BBB) to reach their targets in the central nervous system (CNS) according to a parallel artificial membrane permeation assay for BBB. The result encourages us to study this class of compounds thoroughly and systematically.

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Citations

Sep 23, 2014·Chemico-biological Interactions·Wei ChenHuang Tang
Jan 31, 2015·European Journal of Medicinal Chemistry·Maryam Mohammadi-KhanaposhtaniTahmineh Akbarzadeh
Mar 9, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Wenwen LianGuan-Hua Du
Dec 28, 2017·Journal of Enzyme Inhibition and Medicinal Chemistry·Yao ChenHaopeng Sun
Apr 26, 2014·Advanced Synthesis & Catalysis·Bing ZhengPatrick J Walsh
Mar 7, 2019·Current Topics in Medicinal Chemistry·Ankit GaneshpurkarSushil K Singh
Jul 29, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Agnieszka Zagórska, Anna Jaromin
Jun 17, 2020·Current Topics in Medicinal Chemistry·Vinay KumarKunal Roy
Oct 20, 2020·Bioorganic Chemistry·Sangita Dattatray ShindeNagula Shankaraiah
Mar 17, 2020·Computers in Biology and Medicine·Vinay KumarKunal Roy

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