Artículo
Toward the cholinesterase inhibition potential of TADDOL derivatives: Seminal biological and computational studies
Costantino, Andrea Rosana
; Charbe, Nitin; Duarte, Yorley; Gutiérrez, Margarita; Giordano, Ady; Prasher, Parteek; Dua, Kamal; Mandolesi, Sandra Delia; Zacconi, Flavia Cristina Milagro
Fecha de publicación:
27/07/2022
Editorial:
Wiley VCH Verlag
Revista:
Archiv Der Pharmazie
ISSN:
0365-6233
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Alzheimer's disease (AD) is a degenerative neurological disease characterized by gradual loss of cognitive skills and memory. The exact pathogenesis involved still remains unrevealed, but several studies indicate the involvement of an array of different enzymes, underlining the multifactorial character of the disease. Inhibition of these enzymes is therefore a powerful approach in the development of AD treatments, with promising candidates, including acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and monoamine oxidase. Interestingly, AChE is the target of a major pesticide family (organophosphates), with several reports indicating an intersection between the pesticide's activity and AD. In this study, various TADDOL derivatives were synthesized and their in vitro activities as AChE/BuChE inhibitors as well as their antioxidant activities were studied. Molecular modeling studies revealed the capability of TADDOL derivatives to bind to AChE and induce inhibition, especially compounds 2b and 3c furnishing IC50 values of 36.78 ± 8.97 and 59.23 ± 5.31 µM, respectively. Experimental biological activities and molecular modeling studies clearly demonstrate that TADDOL derivatives with specific stereochemistry have an interesting potential for the design of potent AChE inhibitors. The encouraging results for compounds 2b and 3c indicate them as promising scaffolds for selective and potent AChE inhibitors.
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Articulos(INQUISUR)
Articulos de INST.DE QUIMICA DEL SUR
Articulos de INST.DE QUIMICA DEL SUR
Citación
Costantino, Andrea Rosana; Charbe, Nitin; Duarte, Yorley; Gutiérrez, Margarita; Giordano, Ady; et al.; Toward the cholinesterase inhibition potential of TADDOL derivatives: Seminal biological and computational studies; Wiley VCH Verlag; Archiv Der Pharmazie; 355; 11; 27-7-2022; 1-14
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