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Acetylcholinesterase Inhibition (Potential Anti‐Alzheimer Effects) by Aminobenzoic Acid Derivatives: Synthesis, in Vitro and in Silico Evaluation
Author(s) -
AltamiranoEspino José A.,
SánchezLabastida Luis A.,
MartínezArchundia Marlet,
AndradeJorge Erik,
TrujilloFerrara José G.
Publication year - 2020
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.202003471
Subject(s) - acetylcholinesterase , chemistry , polar effect , in vitro , docking (animal) , in silico , aché , ring (chemistry) , stereochemistry , enzyme , combinatorial chemistry , biochemistry , medicinal chemistry , organic chemistry , medicine , nursing , gene
Alzheimer's disease is a neurodegenerative condition that decreases cognitive function. Thus, intense research efforts have focused on developing acetylcholinesterase (AChE) inhibitors with less side effects. The aim of this study was to synthesize aminobenzoic acid derivatives and test their AChE inhibitory capacity in silico and in vitro. Ten electron‐poor aminobenzoic acid derivatives were synthesized in good‐high yields. Their interaction with EeAChE, according to docking simulations, is mainly mediated by the aromatic ring of the ligands and the catalytic triad of the receptor (π‐π interactions). The in vitro evaluation revealed mixed inhibition (mostly competitive) in all cases. The structural analysis showed better Ki values for heterocyclic than linear compounds and with the presence of two carboxylic groups attached. 5‐Aminoisophthalic acid (AIPA_3, K I =73 μM) showed the lowest K I of all compounds. The electron‐poor aromatic ring of the test compounds is recognized by the electron‐rich peripheric and catalytic binding sites of AChE. AIPA_3, with the best properties, is a promising lead compound for developing new AChE inhibitors.