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.
References
Jul 30, 1982·Science·R T BartusA S Lippa
Apr 1, 1996·Neuron·N C InestrosaJ Garrido
Aug 29, 2001·Biochemistry·G V De FerrariN C Inestrosa
Jul 20, 2002·Science·John Hardy, Dennis J Selkoe
Nov 17, 2004·Current Pharmaceutical Design·J Muñoz-MuriedasF Javier Luque
Oct 20, 2006·Journal of Neuroscience Methods·Mustapha BourhimThomas Nicotera
Dec 27, 2008·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Maria Laura BolognesiCarlo Melchiorre
Citations
Nov 10, 2013·PloS One·Eduardo Sobarzo-SánchezFlorencio M Ubeira
Sep 23, 2014·Chemico-biological Interactions·Wei ChenHuang Tang
Jan 31, 2015·European Journal of Medicinal Chemistry·Maryam Mohammadi-KhanaposhtaniTahmineh Akbarzadeh
Apr 8, 2017·European Journal of Medicinal Chemistry·Jin-Shuai LanYue Ding
Apr 12, 2016·European Journal of Medicinal Chemistry·Chao ZhangXin-Tong Liang
May 10, 2017·Future Medicinal Chemistry·Farzad MehrabiAlireza Foroumadi
Mar 9, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Wenwen LianGuan-Hua Du
Jun 7, 2017·Journal of Enzyme Inhibition and Medicinal Chemistry·Jin-Shuai LanTong Zhang
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
Apr 2, 2019·Natural Product Research·Roque SpinelliAlvaro Sebastián Siano
Jul 29, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Agnieszka Zagórska, Anna Jaromin
Jan 4, 2019·Molecular Diversity·Yusi ChenHuang Tang
Jun 17, 2020·Current Topics in Medicinal Chemistry·Vinay KumarKunal Roy
Oct 20, 2020·Bioorganic Chemistry·Sangita Dattatray ShindeNagula Shankaraiah
Apr 20, 2021·Heliyon·Samaneh ZareiAlireza Foroumadi
Feb 5, 2015·Journal of Medicinal Chemistry·Zhen-Feng ChenHong Liang
Mar 17, 2020·Computers in Biology and Medicine·Vinay KumarKunal Roy
Oct 26, 2016·Bioorganic & Medicinal Chemistry·Shenqi WeiHuang Tang