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Título

Design, synthesis and biological evaluation of new antioxidant and neuroprotective multitarget directed ligands able to block calcium channels

AutorPachòn Angona, Irene; Daniel, Solene; Martin, Hélène; Bonet, Alexandre; Wnorowski, Artur; Maj, Maciej; Jóźwiak, Krzysztof; Silva, Tiago Barros; Refouvelet, Bernard; Borges, Fernanda; Marco-Contelles, José CSIC ORCID; Ismaili, Lhassane
Palabras claveAlzheimer’s disease
Ca2+ channel antagonists
Hantzsch reaction
multitarget directed ligands
Neuroprotection
oxidative stress
Fecha de publicación14-mar-2020
EditorMultidisciplinary Digital Publishing Institute
CitaciónMolecules 25(6): 1329 (2020)
ResumenWe 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.
Versión del editorhttps://doi.org/10.3390/molecules25061329
URIhttp://hdl.handle.net/10261/205638
DOI10.3390/molecules25061329
E-ISSN1420-3049
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