Synthesis and molecular docking studies of 5-trifluoromethoxy-2-indolinones as cholinesterase dual inhibitors.

In Alzheimer's disease, butyrylcholinesterase (BuChE) activity gradually increases, while acetylcholinesterase (AChE) activity decreases or remains unchanged. Dual inhibitors have important roles in regulation of synaptic acetylcholine levels and progression of Alzheimer's disease. 1-(Thiomorpholin-4-ylmethyl)/benzyl-5-trifluoromethoxy-2-indolinones () were synthesized. AChE and BuChE inhibitory effects were investigated with Ellman's method. Molecular docking studies were performed for analyzing the possible binding interactions at active sites. Compound was the strongest inhibitor against both AChE ( = 0.35 μM) and BuChE ( = 0.53 μM). It showed higher inhibitory effects than both donepezil and galantamine. Moreover, compound had a higher inhibitory effect than galantamine and the effect was comparable to that of donepezil against both AChE ( = 0.69 μM) and BuChE ( = 0.95 μM). The benzyl substitution compared with 1-(thiomorpholin-4-ylmethyl) group significantly increased both AChE and BuChE inhibitory effects.