Identification of two arylimides as cholinesterase inhibitors and testing of propranolol addition on impaired rat memory.

Autor: Ciprés-Flores FJ; Academia de Fisiología Humana and Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, México City, Mexico., Farfán-García ED; Academia de Fisiología Humana and Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, México City, Mexico.; Departamento de Bioquímica and Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, México City, Mexico., Andrade-Jorge E; Departamento de Bioquímica and Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, México City, Mexico., Cuevas-Hernández RI; Departamento de Bioquímica and Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, México City, Mexico., Tamay-Cach F; Departamento de Bioquímica and Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, México City, Mexico., Martínez-Archundia M; Laboratorio de Modelado Molecular, Bioinformática y diseño de fármacos, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, México City, Mexico., Trujillo-Ferrara JG; Departamento de Bioquímica and Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, México City, Mexico., Soriano-Ursúa MA; Academia de Fisiología Humana and Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, México City, Mexico.
Jazyk: angličtina
Zdroj: Drug development research [Drug Dev Res] 2020 Apr; Vol. 81 (2), pp. 256-266. Date of Electronic Publication: 2019 Dec 24.
DOI: 10.1002/ddr.21633
Abstrakt: Alzheimer's disease (AD) is clearly linked to the decline of acetylcholine (ACh) effects in the brain. These effects are regulated by the hydrolytic action of acetylcholinesterase (AChE). Therefore, a central palliative treatment of AD is the administration of AChE inhibitors although additional mechanisms are currently described and tested for generating advantageous therapeutic strategies. In this work, we tested new arylamides and arylimides as potential inhibitors of AChE using in silico tools. Then, these compounds were tested in vitro, and two selected compounds, C7 and C8, as well as propranolol showed inhibition of AChE. In addition, they demonstrated an advantageous acute toxicity profile compared to that of galantamine as a reference AChE inhibitor. in vivo evaluation of memory performance enhancement was performed in an animal model of cognitive disturbance with each of these compounds and propranolol individually as well as each compound combined with propranolol. Memory improvement was observed in each case, but without a significant additive effect with the combinations.
(© 2019 Wiley Periodicals, Inc.)
Databáze: MEDLINE
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