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Article

A Novel Tetrahydroacridine Derivative with Potent Acetylcholinesterase Inhibitory Properties and Dissociative Capability against Aβ42 Fibrils Confirmed by In Vitro Studies

by
Ilona Mojzych
1,
Anna Zawadzka
1,
Kryspin Andrzejewski
2,
Monika Jampolska
2,
Zuzana Bednarikova
3,
Miroslav Gancar
3,
Zuzana Gazova
3,
Maciej Mazur
1 and
Katarzyna Kaczyńska
2,*
1
Department of Chemistry, University of Warsaw, Pasteura 1, 02-093 Warsaw, Poland
2
Department of Respiration Physiology, Mossakowski Medical Research Institute, Polish Academy of Sciences, Pawińskiego 5, 02-106 Warsaw, Poland
3
Department of Biophysics, Institute of Experimental Physics, Slovak Academy of Sciences, 04001 Kosice, Slovakia
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2024, 25(18), 10072; https://doi.org/10.3390/ijms251810072
Submission received: 23 August 2024 / Revised: 16 September 2024 / Accepted: 17 September 2024 / Published: 19 September 2024
(This article belongs to the Special Issue Neurodegenerative Diseases: New Insights into Mechanisms, Prevention, Markers, and Therapeutic Targets)
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Abstract

Alzheimer’s disease (AD) is one of the most common causes of dementia, accounting for more than 60% of all cases. It is a neurodegenerative disease in which symptoms such as a decline in memory, thinking, learning, and organizing skills develop gradually over many years and eventually become more severe. To date, there is no effective treatment for the cause of Alzheimer’s disease, and the existing pharmacological options primarily help manage symptoms. Treatment is mainly based on acetylcholinesterase (AChE) inhibitors such as donepezil, rivastigmine, and galantamine, which exhibit numerous adverse cardiovascular and gastrointestinal effects due to excessive stimulation of peripheral cholinergic activity involving muscarinic receptors. Therefore, in addition to the obvious drugs that act on the cause of the disease, new drugs based on AChE inhibition that show the fewest side effects are needed. One potential drug could be a new compound under study, tetrahydroacridine derivative (CHDA), which showed significant potential to inhibit the AChE enzyme in previous in vitro studies. The present study shows that while having very potent AChE inhibitory properties, CHDA is a compound with low toxicity to nerve cell culture and living organisms. In addition, it exhibits dissociative activity against amyloid β fibrils, which is extremely important for applications in Alzheimer’s disease therapy.
Keywords: Alzheimer’s disease; acetylcholinesterase inhibitor; therapy; Aβ fibrils Alzheimer’s disease; acetylcholinesterase inhibitor; therapy; Aβ fibrils

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MDPI and ACS Style

Mojzych, I.; Zawadzka, A.; Andrzejewski, K.; Jampolska, M.; Bednarikova, Z.; Gancar, M.; Gazova, Z.; Mazur, M.; Kaczyńska, K. A Novel Tetrahydroacridine Derivative with Potent Acetylcholinesterase Inhibitory Properties and Dissociative Capability against Aβ42 Fibrils Confirmed by In Vitro Studies. Int. J. Mol. Sci. 2024, 25, 10072. https://doi.org/10.3390/ijms251810072

AMA Style

Mojzych I, Zawadzka A, Andrzejewski K, Jampolska M, Bednarikova Z, Gancar M, Gazova Z, Mazur M, Kaczyńska K. A Novel Tetrahydroacridine Derivative with Potent Acetylcholinesterase Inhibitory Properties and Dissociative Capability against Aβ42 Fibrils Confirmed by In Vitro Studies. International Journal of Molecular Sciences. 2024; 25(18):10072. https://doi.org/10.3390/ijms251810072

Chicago/Turabian Style

Mojzych, Ilona, Anna Zawadzka, Kryspin Andrzejewski, Monika Jampolska, Zuzana Bednarikova, Miroslav Gancar, Zuzana Gazova, Maciej Mazur, and Katarzyna Kaczyńska. 2024. "A Novel Tetrahydroacridine Derivative with Potent Acetylcholinesterase Inhibitory Properties and Dissociative Capability against Aβ42 Fibrils Confirmed by In Vitro Studies" International Journal of Molecular Sciences 25, no. 18: 10072. https://doi.org/10.3390/ijms251810072

APA Style

Mojzych, I., Zawadzka, A., Andrzejewski, K., Jampolska, M., Bednarikova, Z., Gancar, M., Gazova, Z., Mazur, M., & Kaczyńska, K. (2024). A Novel Tetrahydroacridine Derivative with Potent Acetylcholinesterase Inhibitory Properties and Dissociative Capability against Aβ42 Fibrils Confirmed by In Vitro Studies. International Journal of Molecular Sciences, 25(18), 10072. https://doi.org/10.3390/ijms251810072

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