Construction of Spirooxindole Analogues Engrafted with Indole and Pyrazole Scaffolds as Acetylcholinesterase Inhibitors

Abstract

Twenty-five new hits of spirooxindole analogs8a-yengrafted with indole and pyrazole scaffolds were designed and constructedviaa [3+2]cycloaddition (32CA) reaction starting from three components: new chalcone-based indole and pyrazole scaffolds5a-d, substituted isatins6a-c, and secondary amines7a-d. The potency of the compounds were assessed in modulating cholinesterase (AChE) activity using Ellman’s method. Compounds8iand8yshowed the strongest acetylcholine esterase inhibition (AChEI) with IC50values of 24.1 and 27.8 μM, respectively. Molecular docking was used to study their interaction with the active site of hAChE.