Abstract
A series of new oxindole-based spiro-heterocycles bearing the benzo[
b
]thiophene motif were synthesized via a 1,3-dipolar cycloaddition reaction and their acetylcholinesterase (AChE) inhibitory activity was evaluated. All the synthesized compounds exhibited moderate inhibitory activities against AChE, while
IIc
was found to be the most active analog with an IC
50
value of 20,840 µM·L
−1
. Its molecular structure was a 5-chloro-substituted oxindole bearing benzo[
b
]thiophene and octahydroindole moieties. Based on molecular docking studies,
IIc
was strongly bound to the catalytic and peripheral anionic sites of the protein through hydrophilic, hydrophobic, and π-stacking interactions with Asp74, Trp86, Tyr124, Ser125, Glu202, Ser203, Trp236, Trp286, Phe297, Tyr337, and Tyr341. These interactions also indicated that the multiplicity of the
IIc
aromatic core significantly favored its activity.