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Morpholine-based chalcones as dual-acting monoamine oxidase-B and acetylcholinesterase inhibitors: synthesis and biochemical investigations

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....

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Detalles Bibliográficos
Autores principales: Sasidharan, Rani, Eom, Bo Hyun, Heo, Jeong Hyun, Park, Jong Eun, Abdelgawad, Mohamed A., Musa, Arafa, Gambacorta, Nicola, Nicolotti, Orazio, Manju, Sreedharannair Leelabaiamma, Mathew, Bijo, Kim, Hoon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7808749/
https://www.ncbi.nlm.nih.gov/pubmed/33430657
http://dx.doi.org/10.1080/14756366.2020.1842390
Descripción
Sumario: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.