Development of Neuroprotective Agents for the Treatment of Alzheimer's Disease using Conjugates of Serotonin with Sesquiterpene Lactones
- Authors: Neganova M.1, Liu J.1, Aleksandrova Y.2, Vasilieva N.2, Semakov A.2, Yandulova E.2, Sukocheva O.3, Balakin K.4, Klochkov S.2, Fan R.1
-
Affiliations:
- Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University
- , Institute of Physiologically Active Compounds of Russian Academy of Sciences
- Discipline of Health Sciences, College of Nursing and Health Sciences,, Flinders University
- , Moscow Institute of Physics and Technology (National Research University)
- Issue: Vol 31, No 5 (2024)
- Pages: 529-551
- Section: Anti-Infectives and Infectious Diseases
- URL: https://rjmseer.com/0929-8673/article/view/645161
- DOI: https://doi.org/10.2174/0929867330666221125105253
- ID: 645161
Cite item
Full Text
Abstract
Background:Sesquiterpene lactones are secondary plant metabolites with a wide variety of biological activities. The process of lactone conjugation to other pharmacophores can increase the efficacy and specificity of the conjugated agent effect on molecular targets in various diseases, including brain pathologies. Derivatives of biogenic indoles, including neurotransmitter serotonin, are of considerable interest as potential pharmacophores. Most of these compounds have neurotropic activity and, therefore, can be used in the synthesis of new drugs with neuroprotective properties.
Aim:The aim of this experimental synthesis was to generate potential treatment agents for Alzheimer's disease using serotonin conjugated with natural sesquiterpene lactones.
Methods:Three novel compounds were obtained via the Michael reaction and used for biological testing. The obtained conjugates demonstrated complex neuroprotective activities. Serotonin conjugated to isoalantolactone exhibited strong antioxidant and mitoprotective activities.
Results:The agent was also found to inhibit β-site amyloid precursor protein cleaving enzyme 1 (BACE-1), prevent the aggregation of β-amyloid peptide 1-42, and protect SH-SY5Y neuroblastoma cells from neurotoxins such as glutamate and H2O2. In a transgenic animal model of Alzheimer's disease (5xFAD line), the conjugated agent restored declined cognitive functions and improved learning and memory.
Conclusion:In conclusion, the obtained results indicate that serotonin conjugates to sesquiterpene lactones are promising agents for the treatment of symptoms associated with Alzheimer's disease.
About the authors
Margarita Neganova
Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University
Email: info@benthamscience.net
Junqi Liu
Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University
Email: info@benthamscience.net
Yulia Aleksandrova
, Institute of Physiologically Active Compounds of Russian Academy of Sciences
Email: info@benthamscience.net
Natalia Vasilieva
, Institute of Physiologically Active Compounds of Russian Academy of Sciences
Email: info@benthamscience.net
Alexey Semakov
, Institute of Physiologically Active Compounds of Russian Academy of Sciences
Email: info@benthamscience.net
Ekaterina Yandulova
, Institute of Physiologically Active Compounds of Russian Academy of Sciences
Email: info@benthamscience.net
Olga Sukocheva
Discipline of Health Sciences, College of Nursing and Health Sciences,, Flinders University
Author for correspondence.
Email: info@benthamscience.net
Konstantin Balakin
, Moscow Institute of Physics and Technology (National Research University)
Email: info@benthamscience.net
Sergey Klochkov
, Institute of Physiologically Active Compounds of Russian Academy of Sciences
Email: info@benthamscience.net
Ruitai Fan
Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University
Author for correspondence.
Email: info@benthamscience.net
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