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The inhibition of cholinesterases plays a crucial role in a therapy of neurodegenerative diseases, including Alzheimer's disease. Especially, butyrylcholinesterase (BChE) has recently gained special interest. On the other hand, compounds having antioxidative properties may have a beneficial role in slowing down neurodegeneration processes. To combine these two effects, we synthesized a series of new derivatives of melatonin, which is a strong antioxidant, possessing structural elements essential for the inhibitory activity against cholinesterase. The structure of the new compounds was confirmed by NMR spectroscopy and mass spectrometry, and their activity against cholinesterases was measured in vitro using modified Ellman's method. The compounds obtained showed a high inhibitory activity, together with a strong selectivity against BChE. These results may point at new area of interest in a research on cholinesterase inhibitors.