Isoxazoles: synthesis, evaluation and bioinformatic design as acetylcholinesterase inhibitors

Abstract

Our research provided enough evidence of the efficacy of isoxazoles as AChE inhibitors. The isoxazoles were synthesized and evaluated as inhibitors of AChE. The docking study based on a novel series of complexes isoxazole with AChE from Electroporus electricus has demonstrated that the ligand bind is similar to the compounds used as reference. To find new candidates with the isoxazole core that act as inhibitors of AChE, part of the structure of the compound 9 was used for de-novo design. Molecular docking models of the ligand-AChE complexes suggest that the compound 10 is located on the periphery of the AChE active site.

Novel N‐allyl/propargyl tetrahydroquinolines: Synthesis via Three‐component Cationic Imino Diels–Alder Reaction, Binding Prediction, and Evaluation as Cholinesterase Inhibitors

“…A p value, <0.05, was considered significant. Details for pharmacological experiments are described in Experimental section as well as in previous reports . Although the biological activity of compounds was poor, when compared to the reference employed, it was proved that synthesized compounds could be starting scaffolds used as interesting pharmacophores for the design of new biologically active compounds against enzymes related with neurodegenerative diseases.…”

The synthetic and therapeutic expedition of isoxazole and its analogs

“…18) also possessed a disease-modifying role in Alzheimer's disease. Gutiérrez et al (2013) synthesized some 3,5-disubstituted isoxazole derivatives, tested for their in vitro AChE inhibitory activity and performed their docking study. Compounds 95 and 96 ( Fig.…”

The Isoxazole Ring and Its N‐Oxide: A Privileged Core Structure in Neuropsychiatric Therapeutics

“…[84] 3,5-Disubstituted isoxazoles 17 ( Figure 6) used as AChR inhibitors for AD, have been found active as partial agonists in the treatment of depression. [85] Sazetidine-A isoxazole-based analogues 18 (Figure 7) have also been shown to be effective as selective a 4 b 2 nAChR partial agonists in the treatment of depression. [86] Isoxazoles have been reported as potent atypical antipsychotics, [87] particularly those of as econd generation, as partial agonists of D 2 and 5-HT 1A receptors and antagonists of 5-HT 2A receptors.…”