Design, Synthesis, Biological Activity, and Molecular Modeling of Novel Spiroquinazoline Derivatives as Acetylcholinesterase Inhibitors for Alzheimer Disease

Abstract

The p-toluene sulfonic acid (p-TSA) catalyzed cascade ring closing transformation has been executed for the preparation of novel spiroquinazolinone compounds 4 and 5 by the reaction between anthranilamide and cyclohexanone followed by subsequent acylation. These molecules were then examined against the inhibitory activity of Acetylcholineterase (AchE). The tested compounds revealed moderate anti-AChE activity of IC50 values ranging from 46.675 to 14.256 µM). The described results lead toward the development of compounds 4b and 5c having promising anti-AChE activities with IC50 values at the micromolar level. The docking study suggests that these hybrid spiroquinazolinone scaffold might facilitate the further development of investigated compounds as anti-Alzheimer agents.