Tacrine-propargylamine derivatives with improved acetylcholinesterase inhibitory activity and lower hepatotoxicity as a potential lead compound for the treatment of Alzheimer's disease

Journal of Enzyme Inhibition and Medicinal Chemistry
Fei MaoXingshu Li

Abstract

A series of tacrine-propargylamine derivatives were synthesised and evaluated as possible anti-Alzheimer's disease (AD) agents. Among these derivatives, compounds 3a and 3b exhibited superior activities and a favourable balance of AChE and BuChE activities (3a: IC50 values of 51.3 and 77.6 nM; 3b: IC50 values of 11.2 and 83.5 nM). Compounds 3a and 3b also exhibited increased hAChE inhibitory activity compared with tacrine by approximately 5- and 28-fold, respectively, and low neurotoxicity. Importantly, these compounds also had lower hepatotoxicity than tacrine. Based on these results, compounds 3a and 3b could be considered as potential lead compounds for the treatment of AD and other AChE related diseases, such as schizophrenia, glaucoma and myasthenia gravis.

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Citations

Apr 15, 2016·Journal of Enzyme Inhibition and Medicinal Chemistry·Burhanettin TuranClaudiu T Supuran
May 16, 2017·Future Medicinal Chemistry·Damijan KnezStanislav Gobec
Jan 18, 2017·Journal of Enzyme Inhibition and Medicinal Chemistry·Fatih SonmezSalvatore Guccione
Dec 7, 2017·Journal of Enzyme Inhibition and Medicinal Chemistry·Kamila CzarneckaPaweł Szymański
Dec 13, 2018·Neural Regeneration Research·Mostafa M Ibrahim, Moustafa T Gabr
Jan 27, 2019·International Journal of Molecular Sciences·Kamila CzarneckaPaweł Szymański
Aug 23, 2020·International Journal of Molecular Sciences·Todd J EckroatSeth C Cowan
Mar 2, 2021·Organic & Biomolecular Chemistry·Quelli Larissa Oliveira de SantanaEmil Lindbäck
Jul 17, 2019·Medicinal Chemistry·Maja PrzybyłowskaMateusz Daśko
Jun 15, 2021·Pharmacological Reports : PR·Karolina MaciejewskaPaweł Szymański
Nov 23, 2017·Chemical Reviews·Kate LauderDaniele Castagnolo

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