Tacrine – benzothiazoles: novel class of potential multitarget anti-Alzheimer's drugs dealing with cholinergic, amyloid and mitochondrial systems

0561212 - FZÚ 2023 RIV US eng J - Journal Article
Nepovímová, E. - Svobodová, L. - Doležal, R. - Rostohar, Danijela … Total 30 authors
Tacrine – benzothiazoles: novel class of potential multitarget anti-Alzheimer's drugs dealing with cholinergic, amyloid and mitochondrial systems.
Bioorganic Chemistry. Roč. 107, Feb (2021), č. článku 104596. ISSN 0045-2068. E-ISSN 1090-2120
EU Projects: European Commission(XE) 654148 - LASERLAB-EUROPE
Institutional support: RVO:68378271
Keywords : Alzheimer's disease * tacrine * benzothiazole * acetylcholinesterase Inhibitors * amyloid beta * ABAD * MTDLs
OECD category: Optics (including laser optics and quantum optics)
Impact factor: 5.307, year: 2021
Method of publishing: Limited access
https://doi.org/10.1016/j.bioorg.2020.104596

A series of tacrine – benzothiazole hybrids incorporate inhibitors of acetylcholinesterase (AChE), amyloid β (Aβ) aggregation and mitochondrial enzyme ABAD, whose interaction with Aβ leads to mitochondrial dysfunction, into a single molecule. In vitro, several of 25 final compounds exerted excellent anti-AChE properties and interesting capabilities to block Aβ aggregation. The best derivative of the series could be considered 10w that was found to be highly potent and selective towards AChE with the IC50 value in nanomolar range. Moreover, the same drug candidate exerted absolutely the best results of the series against ABAD, decreasing its activity by 23% at 100 µM concentration. Regarding the cytotoxicity profile of highlighted compound, it roughly matched that of its parent compound – 6-chlorotacrine. Finally, 10w was forwarded for in vivo scopolamine-induced amnesia experiment consisting of Morris Water Maze test, where it demonstrated mild procognitive effect.

Permanent Link: https://hdl.handle.net/11104/0333898