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

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 ?M), showing significant neuroprotection (38%) against H₂O₂ at 10 ?M, being considered thus a hit-compound for further investigation in our search for anti-Alzheimer's disease agents.

SUBMITTER: Pachon Angona I 

PROVIDER: S-EPMC7144121 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature