Design, Synthesis and Biological Evaluation of New Antioxidant and Neuroprotective Multitarget Directed Ligands Able to Block Calcium Channels - Archive ouverte HAL Access content directly
Journal Articles Molecules Year : 2020

Design, Synthesis and Biological Evaluation of New Antioxidant and Neuroprotective Multitarget Directed Ligands Able to Block Calcium Channels

, , , , , , , , , , , (1)
1
Irene Pachòn Angona
  • Function : Author
Solene Daniel
  • Function : Author
Helene Martin
  • Function : Author
Alexandre Bonet
  • Function : Author
Artur Wnorowski
Maciej Maj
Krzysztof Jóźwiak
Tiago Barros Silva
  • Function : Author
Bernard Refouvelet
  • Function : Author
Fernanda Borges
José Marco-Contelles

Abstract

We report herein the design, synthesis and biological evaluation of new antioxidant and neuroprotective multitarget directed ligands (MTDLs) able to block Ca2+ channels. New dialkyl 2,6-dimethyl-4-(4-(prop-2-yn-1-yloxy)phenyl)-1,4-dihydropyridine-3,5-dicarboxylate MTDLs 3a–t, resulting from the juxtaposition of nimodipine, a Ca2+ channel antagonist, and rasagiline, a known MAO inhibitor, have been obtained from appropriate and commercially available precursors using a Hantzsch reaction. Pertinent biological analysis has prompted us to identify the MTDL 3,5-dimethyl-2,6–dimethyl–4-[4-(prop–2–yn–1-yloxy)phenyl]-1,4-dihydro- pyridine- 3,5-dicarboxylate (3a), as an attractive antioxidant (1.75 TE), Ca2+ channel antagonist (46.95% at 10 μM), showing significant neuroprotection (38%) against H2O2 at 10 μM, being considered thus a hit-compound for further investigation in our search for anti-Alzheimer’s disease agents.

Dates and versions

hal-03654614 , version 1 (28-04-2022)

Identifiers

Cite

Irene Pachòn Angona, Solene Daniel, Helene Martin, Alexandre Bonet, Artur Wnorowski, et al.. Design, Synthesis and Biological Evaluation of New Antioxidant and Neuroprotective Multitarget Directed Ligands Able to Block Calcium Channels. Molecules, 2020, 25 (6), pp.1329. ⟨10.3390/molecules25061329⟩. ⟨hal-03654614⟩

Collections

UNIV-FCOMTE
6 View
0 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More