Antioxidant and acetylcholinesterase inhibition activity of aliphatic and aromatic edaravone derivatives
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Medicinal Chemistry Research https://doi.org/10.1007/s00044-020-02667-5
ORIGINAL RESEARCH
Antioxidant and acetylcholinesterase inhibition activity of aliphatic and aromatic edaravone derivatives Victor Wagner Barajas-Carrillo1 Arturo Estolano-Cobián1 Laura Díaz-Rubio1 Rocío Rosario Ayllón-Gutiérrez1 Ricardo Salazar-Aranda2 Raúl Díaz-Molina3 Víctor García-González3 Horacio Almanza-Reyes4 Ignacio A. Rivero5 Joaquín G. Marrero6 Iván Córdova-Guerrero 1 ●
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Received: 16 September 2020 / Accepted: 5 November 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract As Alzheimer disease (AD) is a multifactorial condition, it should be tackled with drugs targeting multiple key pathways. A series of aliphatic (2–8) and aromatic (9–15) edaravone derivatives were synthesized, characterized, and evaluated as antioxidant agents using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2-2’-azino-bis-(3-ethylbenzothiazoline-6-sulfonate) (ABTS·+) assays, as well as acetylcholinesterase (AChE) inhibitors. In both antioxidant assays, even though the starting compound edaravone was more active, the best derivative was 5 with 50% effective concentration (EC50) of 0.0301 and 0.8106 mM respectively, followed by 3 (EC50 of 0.1920 mM and 3.5311 mM). In the AChE inhibition assay, the derivatives were not as active as the positive control galantamine, but a general better activity was shown from the aromatic compounds. The best results were for 10, with 41.9% of inhibition (concentration of 150 μg/mL), and 9 with 31.6%. Docking analysis of compound 10 showed hydrogen bonds with residues Ser200 and His440 in the AChE catalytic gorge. All synthesized derivatives 2–15 presented drug-like properties and are capable of crossing the blood–brain barrier and not be pumped out of it. These results indicate edaravone derivatives can function as scaffolds for AD drugs, though further derivatizations should be conducted to improve their antioxidant and AChE inhibition profiles. Graphical Abstract
Supplementary information The online version of this article (https:// doi.org/10.1007/s00044-020-02667-5) contains supplementary material, which is available to authorized users. * Iván Córdova-Guerrero [email protected]
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Facultad de Medicina y Psicología, Universidad Autónoma de Baja California, 22390 Tijuana, B.C., Mexico
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Facultad de Ciencias Químicas e Ingeniería, Universidad Autónoma de Baja California, 22390 Tijuana, B.C., Mexico
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Departamento de Química Analítica, Facultad de Medicina, Universidad Autónoma de Nuevo León, San Nicolás de los Garza, 64460 Monterrey, Mexico
Centro de Graduados e Investigación en Química, Tecnológico Nacional de México/Instituto Tecnológico de Tijuana, 22510 Tijuana, B.C., Mexico
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Instituto Politécnico Nacional, UPIIG, Silao de la Victoria, Guanajuato, Mexico
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Departamento de Bioquímica, Facultad de Medicina Mexicali, Universidad Autónoma de Baja California, 21000 Mexicali, Mexico
Medicinal Chemistry Research
Keywords Edar
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