Synthesis and biological evaluation of novel N-substituted (3-(1-aminoethylidene)-2-oxochroman-4-yl)phosphonic acid diethyl ester derivatives as anti-Alzheimer agent

Shaikh, Sarfaraz; Pavale, Ganesh; Ramana, M. M. V.

doi:10.1007/s11696-020-01099-0

Cited by 4 publications

(1 citation statement)

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“…[54][55][56][57][58][59][60][61][62] Moreover, several studies focused on the development of ester derivatives of different scaffolds to increase enzyme interactions. [63][64][65][66] Remarkably, TADDOL derivatives were never studied for their AChE inhibition potential and antioxidant activities, although they are structurally highly interesting. Herein, we wish to fill this gap, and report on the synthesis of several TADDOL derivatives and their respective antioxidant and AChE inhibition activities, including some structurally unprecedented phthalimide and saccharine congeners.…”

Section: Introductionmentioning

confidence: 99%

Toward the cholinesterase inhibition potential of TADDOL derivatives: Seminal biological and computational studies

Constantino

Charbe

Duarte

et al. 2022

Archiv der Pharmazie

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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 IC 50 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

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