Exploring the Potential of Sulfonamide-Dihydropyridine Hybrids as Multitargeted Ligands for Alzheimer's Disease Treatment

Alzheimer's disease (AD) is a multifactorial neurodegenerative disease that has a heavy social and economic impact on all societies and for which there is still no cure. Multitarget-directed ligands (MTDLs) seem to be a promising therapeutic strategy for finding an effective treatment for this...

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Bibliographic Details
Published in:International journal of molecular sciences 2023-06, Vol.24 (11), p.9742
Main Authors: Dakhlaoui, Imen, Bernard, Paul J, Pietrzak, Diana, Simakov, Alexey, Maj, Maciej, Refouvelet, Bernard, Béduneau, Arnaud, Cornu, Raphaël, Jozwiak, Krzysztof, Chabchoub, Fakher, Iriepa, Isabel, Martin, Helene, Marco-Contelles, José, Ismaili, Lhassane
Format: Article
Language:English
Subjects:
Advertising executives
Alzheimer's disease
Antioxidants
Apoptosis
Biological activity
Biological effects
Brain
Calcium
calcium channel antagonism
Calcium channels
Care and treatment
Catalytic oxidation
Chemical Sciences
Cholinesterase
cholinesterase inhibition
Dementia
Dihydropyridine
Economic impact
Enzymes
Hantzsch reaction
Hybrids
Impact analysis
Kinases
Life Sciences
Ligands
multitarget directed ligands
Neurons
Neurophysiology
Nrf2
Pathogenesis
Peptides
Phosphorylation
Proteins
Sulfonamides
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Summary:Alzheimer's disease (AD) is a multifactorial neurodegenerative disease that has a heavy social and economic impact on all societies and for which there is still no cure. Multitarget-directed ligands (MTDLs) seem to be a promising therapeutic strategy for finding an effective treatment for this disease. For this purpose, new MTDLs were designed and synthesized in three steps by simple and cost-efficient procedures targeting calcium channel blockade, cholinesterase inhibition, and antioxidant activity. The biological and physicochemical results collected in this study allowed us the identification two sulfonamide-dihydropyridine hybrids showing simultaneous cholinesterase inhibition, calcium channel blockade, antioxidant capacity and Nrf2-ARE activating effect, that deserve to be further investigated for AD therapy.
ISSN:1422-0067
1661-6596
1422-0067
1661-6596
DOI:10.3390/ijms24119742