Design and Synthesis of Multi-Functional Ligands through Hantzsch Reaction: Targeting Ca[sup.2+] Channels, Activating Nrf2 and Possessing Cathepsin S Inhibitory, and Antioxidant Properties

This work relates to the design and synthesis of a series of novel multi-target directed ligands (MTDLs), i.e., compounds 4a–l, via a convenient one-pot three-component Hantzsch reaction. This approach targeted calcium channel antagonism, antioxidant capacity, cathepsin S inhibition, and interferenc...

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Bibliographic Details
Published in:Pharmaceutics 2024-01, Vol.16 (1)
Main Authors: Pachón-Angona, Irene, Bernard, Paul J, Simakov, Alexey, Maj, Maciej, Jozwiak, Krzysztof, Novotna, Anna, Lemke, Carina, Gütschow, Michael, Ma, Oset-Gasque, María-Jesús, Contelles, José-Marco, Ismaili, Lhassane
Format: Article
Language:English
Subjects:
Alzheimer's disease
Antioxidants
Calcium channels
Cathepsins
Ethylenediaminetetraacetic acid
Nervous system diseases
Rasagiline
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Summary:This work relates to the design and synthesis of a series of novel multi-target directed ligands (MTDLs), i.e., compounds 4a–l, via a convenient one-pot three-component Hantzsch reaction. This approach targeted calcium channel antagonism, antioxidant capacity, cathepsin S inhibition, and interference with Nrf2 transcriptional activation. Of these MTDLs, 4i emerged as a promising compound, demonstrating robust antioxidant activity, the ability to activate Nrf2-ARE pathways, as well as calcium channel blockade and cathepsin S inhibition. Dihydropyridine 4i represents the first example of an MTDL that combines these biological activities.
ISSN:1999-4923
1999-4923
DOI:10.3390/pharmaceutics16010121