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The oxindole core is an important structural motif in many natural and synthetic substances with various biological activities including anticancer, antineurodegenerative, and antimicrobial properties. This report focuses on the synthesis and biological activity of a series of novel N-substituted 3-aminooxindoles and their assessment in cholinesterase (ChE) and monoamine oxidase (MAO) inhibition. With regard to MAO inhibition, a series of N-propargyl containing derivatives was synthesized and screened. Despite being weak inhibitors of MAO-A and MAO-B, the compounds were selective for butyrylcholinesterase (BuChE) over acetylcholinesterase (AChE). Most of them were strong inhibitors of BuChE with IC50's of less than 1 µM, and one compound showed an IC50 = 27 nM. The mechanism of action of the inhibition was pin-pointed through molecular modeling, and was validated using saturation-transfer-difference (STD) NMR. Some of the compounds were screened for anti-oxidant properties, but showed no activity. The same compounds were screened in the neurodegenerative disease model cell-line SH-SY5Y and although some were found to be non-cytotoxic, others were moderately cytotoxic. Continuous live cell imaging experiments showed that the compounds do not induce relevant cell damage and thus, the compounds might be interesting drug candidates for Alzheimer’s disease. Furthermore, the most active compounds showed excellent drug-likeness and pharmacological properties predicted using Swiss-ADME, and the pharmacokinetic simulations indicated that all these compounds cross the blood-brain-barrier.