Sasidharan_2021_J.Enzyme.Inhib.Med.Chem_36_188

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 microM, followed by MO7 (0.25 microM). MO5 most potently inhibited AChE (IC(50) = 6.1 microM), followed by MO9 (IC(50) = 12.01 microM) and MO7 most potently inhibited MAO-A (IC(50) = 7.1 microM). MO1 was a reversible mixed-type inhibitor of MAO-B (K(i) = 0.018 microM); MO5 reversibly competitively inhibited AChE (K(i) = 2.52 microM); and MO9 reversibly noncompetitively inhibited AChE (K(i) = 7.04 microM). 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.