Isoindolone derivatives as novel potential anti-Alzheimer's candidates: synthesis, in silico, and AChE inhibitory activity evaluation
Por:
Andrade-Jorge, Erik, Rivera-Sanchez, Fernando, Rodriguez, Jessica E., Lagos-Cruz, Jesus A., Reyes-Vallejo, Natalia, Villalobos-Molina, Rafael, Gallardo-Ortiz, Itzell A., Reyes-Ramirez, Adelfo
Publicada:
1 jun 2022
Resumen:
Alzheimer's disease (AD) is a neurodegenerative condition that affects
elderly persons around the world, impairing cognitive function, due to a
decrease in cholinergic transmission. Thus, developing drugs with better
acetylcholinesterase (AChE) inhibitory characteristics will improve
cholinergic transmission. This work aimed to synthesize isoindolone
derivatives and test their AChE inhibitory activity both in silico and
in vitro, and to compare them with their precursors. Seven racemic
mixtures (isoindolones) and four precursors were synthesized in good
yields. Their interaction with AChE is mainly mediated by the aromatic
ring and the ester group, according to molecular docking. The in vitro
experiments revealed competitive inhibition for all tested molecules.
The structural analysis showed better Ki values for structures with an
extra double bond, and the two ester groups. Racemic mixture rac-6
showed the lowest Ki (55.4 mu M) of all compounds. Both aromatic ring
moieties and two ester groups in the isoindolone derivatives play an
important role in recognition with AChE.
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Filiaciones:
Andrade-Jorge, Erik:
Univ Nacl Autonoma Mexico, Fac Estudios Super Iztacala, Unidad Invest Biomed & Carrera Enfermeria, Av de Los Barrios 1, Tlalnepantla 54090, Estado De Mexic, Mexico
Inst Politecn Nacl, Lab Invest Bioquim, Secc Estudios Posgrad & Invest, Escuela Super Med, Plan De San Luis & Diaz Miron S-N Casco De Santo, Mexico City 11340, DF, Mexico
Rivera-Sanchez, Fernando:
Univ Nacl Autonoma Mexico, Fac Estudios Super Zaragoza, Unidad Multidisciplinaria Invest Expt, Batalla 5 Mayo S-N Esquina Fuerte de Loreto, Mexico City 09230, DF, Mexico
Rodriguez, Jessica E.:
Univ Autonoma Estado Morelos, Lab Farmacognosia, Fac Farm, Ave Univ 1001, Cuernavaca 62209, Morelos, Mexico
Univ Nacl Autonoma Mexico, Fac Estudios Super Zaragoza, Bioquim Clin, Carrera Quim Farmaceut Biol, Av Guelatao Con Av Exploradores, Mexico City 09230, DF, Mexico
Lagos-Cruz, Jesus A.:
Univ Nacl Autonoma Mexico, Fac Estudios Super Iztacala, Unidad Invest Biomed & Carrera Enfermeria, Av de Los Barrios 1, Tlalnepantla 54090, Estado De Mexic, Mexico
Inst Politecn Nacl, Lab Invest Bioquim, Secc Estudios Posgrad & Invest, Escuela Super Med, Plan De San Luis & Diaz Miron S-N Casco De Santo, Mexico City 11340, DF, Mexico
Reyes-Vallejo, Natalia:
Univ Nacl Autonoma Mexico, Fac Estudios Super Zaragoza, Unidad Multidisciplinaria Invest Expt, Batalla 5 Mayo S-N Esquina Fuerte de Loreto, Mexico City 09230, DF, Mexico
Villalobos-Molina, Rafael:
Univ Nacl Autonoma Mexico, Fac Estudios Super Iztacala, Unidad Invest Biomed & Carrera Enfermeria, Av de Los Barrios 1, Tlalnepantla 54090, Estado De Mexic, Mexico
Gallardo-Ortiz, Itzell A.:
Univ Nacl Autonoma Mexico, Fac Estudios Super Iztacala, Unidad Invest Biomed & Carrera Enfermeria, Av de Los Barrios 1, Tlalnepantla 54090, Estado De Mexic, Mexico
Reyes-Ramirez, Adelfo:
Univ Nacl Autonoma Mexico, Fac Estudios Super Zaragoza, Unidad Multidisciplinaria Invest Expt, Batalla 5 Mayo S-N Esquina Fuerte de Loreto, Mexico City 09230, DF, Mexico
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