%0 Journal Article
%T Design and Synthesis of Multi-Functional Ligands through Hantzsch Reaction: Targeting Ca2+ Channels, Activating Nrf2 and Possessing Cathepsin S Inhibitory, and Antioxidant Properties.
%A Pachón-Angona I
%A Bernard PJ
%A Simakov A
%A Maj M
%A Jozwiak K
%A Novotna A
%A Lemke C
%A Gütschow M
%A Martin H
%A Oset-Gasque MJ
%A Contelles JM
%A Ismaili L
%J Pharmaceutics
%V 16
%N 1
%D 2024 Jan 17
%M 38258131
%F 6.525
%R 10.3390/pharmaceutics16010121
%X 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.