Design and Synthesis of Multi-Functional Ligands through Hantzsch Reaction: Targeting Ca<sup>2+</sup> Channels, Activating Nrf2 and Possessing Cathepsin S Inhibitory, and Antioxidant Properties
oleh: Irene Pachón-Angona, Paul J. Bernard, Alexey Simakov, Maciej Maj, Krzysztof Jozwiak, Anna Novotna, Carina Lemke, Michael Gütschow, Helene Martin, María-Jesús Oset-Gasque, José-Marco Contelles, Lhassane Ismaili
| Format: | Article |
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| Diterbitkan: | MDPI AG 2024-01-01 |
Deskripsi
This work relates to the design and synthesis of a series of novel multi-target directed ligands (MTDLs), i.e., compounds <b>4a</b>–<b>l</b>, 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, <b>4i</b> 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 <b>4i</b> represents the first example of an MTDL that combines these biological activities.