Abstract
Nine compounds (MO1-MO9) containing the morpholine moiety were assessed for their inhibitory activities against monoamine oxidases (MAOs) and acetylcholinesterase (AChE). Most of the compounds potently inhibited MAO-B; MO1 most potently inhibited with an IC
50
value of 0.030 µM, followed by MO7 (0.25 µM). MO5 most potently inhibited AChE (IC
50
= 6.1 µM), followed by MO9 (IC
50
= 12.01 µM) and MO7 most potently inhibited MAO-A (IC
50
= 7.1 µM). MO1 was a reversible mixed-type inhibitor of MAO-B (K
i
= 0.018 µM); MO5 reversibly competitively inhibited AChE (K
i
= 2.52 µM); and MO9 reversibly noncompetitively inhibited AChE (K
i
= 7.04 µM). MO1, MO5 and MO9 crossed the blood-brain barrier, and were non-toxic to normal VERO cells. These results show that MO1 is a selective inhibitor of MAO-B and that MO5 is a dual-acting inhibitor of AChE and MAO-B, and that both should be considered candidates for the treatment of Alzheimer's disease.