Morpholine-based chalcones as dual-acting monoamine oxidase-B and acetylcholinesterase inhibitors: synthesis and biochemical investigations
| Autor: | Arafa Musa, Orazio Nicolotti, Rani Sasidharan, Jong Eun Park, Sreedharannair Leelabaiamma Manju, Hoon Kim, Bo Hyun Eom, Bijo Mathew, Mohamed A. Abdelgawad, Jeong Hyun Heo, Nicola Gambacorta |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Monoamine Oxidase Inhibitors
Aché Stereochemistry Monoamine oxidase Morpholines Short Communication RM1-950 Inhibitory postsynaptic potential 01 natural sciences chemistry.chemical_compound Structure-Activity Relationship Chalcones Morpholine Drug Discovery Chlorocebus aethiops dual-acting inhibitor Moiety Animals Humans monoamine oxidase Vero Cells Pharmacology Dose-Response Relationship Drug Molecular Structure 010405 organic chemistry Chemistry General Medicine Hydrogen Peroxide acetylcholinesterase morpholine-containing chalcone Acetylcholinesterase language.human_language 0104 chemical sciences Molecular Docking Simulation 010404 medicinal & biomolecular chemistry Monoamine neurotransmitter language Monoamine oxidase B Cholinesterase Inhibitors Therapeutics. Pharmacology Reactive Oxygen Species docking analysis HeLa Cells Research Article |
| Zdroj: | Journal of Enzyme Inhibition and Medicinal Chemistry, Vol 36, Iss 1, Pp 188-197 (2021) Journal of Enzyme Inhibition and Medicinal Chemistry article-version (VoR) Version of Record |
| ISSN: | 1475-6374 1475-6366 |
| Popis: | 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 IC50 value of 0.030 µM, followed by MO7 (0.25 µM). MO5 most potently inhibited AChE (IC50 = 6.1 µM), followed by MO9 (IC50 = 12.01 µM) and MO7 most potently inhibited MAO-A (IC50 = 7.1 µM). MO1 was a reversible mixed-type inhibitor of MAO-B (Ki = 0.018 µM); MO5 reversibly competitively inhibited AChE (Ki = 2.52 µM); and MO9 reversibly noncompetitively inhibited AChE (Ki = 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. |
| Databáze: | OpenAIRE |
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