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Sixteen compounds were synthesized <jats:italic>via<\/jats:italic> 7\u2010amino\u20104\u2010methylcoumarin acylation, and <jats:italic>in\u2005vitro<\/jats:italic> evaluation of the molecules against <jats:italic>h<\/jats:italic>MAO\u2010A, <jats:italic>h<\/jats:italic>MAO\u2010B, <jats:italic>h<\/jats:italic>AChE, <jats:italic>h<\/jats:italic>BuChE and <jats:italic>h<\/jats:italic>BACE1 was performed. Five compounds turned out to be potent and selective <jats:italic>h<\/jats:italic>MAO\u2010B inhibitors in the nanomolar range, six displayed inhibitory activity of <jats:italic>h<\/jats:italic>MAO\u2010A in the low micromolar range, one showed <jats:italic>h<\/jats:italic>AChE inhibitory activity and another one <jats:italic>h<\/jats:italic>BACE1 inhibitory activity. MAO\u2010B reversibility profile of 7\u2010(4\u2019\u2010chlorobenzamido)\u20104\u2010methylcoumarin (<jats:bold>10<\/jats:bold>) was investigated, with this compound being a reversible inhibitor. Neurotoxicity on motor cortex neurons and neuroprotection against H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> were also studied, corroborating the safety profile of these molecules. Finally, theoretical ADME properties were also calculated, showing these molecules as good candidates for the optimization of a lead compound. Results suggest that by modulating the substitution pattern at position 7 of the scaffold, selective or multitarget molecules can be achieved.<\/jats:p>","DOI":"10.1002\/cmdc.202000454","type":"journal-article","created":{"date-parts":[[2020,7,23]],"date-time":"2020-07-23T03:40:13Z","timestamp":1595475613000},"page":"179-186","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["7\u2010Amidocoumarins as Multitarget Agents against Neurodegenerative Diseases: Substitution Pattern Modulation"],"prefix":"10.1002","volume":"16","author":[{"given":"Fernanda","family":"Rodr\u00edguez\u2010Enr\u00edquez","sequence":"first","affiliation":[{"name":"Chronic Diseases Pharmacology Group Center for Research in Molecular Medicine and Chronic Diseases (CIMUS) University of Santiago de Compostela  15782 Santiago de Compostela Spain"},{"name":"Departamento de Farmacolog\u00eda, Farmacia y Tecnolog\u00eda Farmac\u00e9utica Universidade de Santiago de Compostela  15782 Santiago de Compostela Spain"}]},{"given":"Dolores","family":"Vi\u00f1a","sequence":"additional","affiliation":[{"name":"Chronic Diseases Pharmacology Group Center for Research in Molecular Medicine and Chronic Diseases (CIMUS) University of Santiago de Compostela  15782 Santiago de Compostela Spain"},{"name":"Departamento de Farmacolog\u00eda, Farmacia y Tecnolog\u00eda Farmac\u00e9utica Universidade de Santiago de Compostela  15782 Santiago de Compostela Spain"}]},{"given":"Eugenio","family":"Uriarte","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Org\u00e1nica Facultade de Farmacia Universidade de Santiago de Compostela  15782 Santiago de Compostela Spain"},{"name":"Instituto de Ciencias Qu\u00edmicas Aplicadas Universidad Aut\u00f3noma de Chile  7500912 Santiago Chile"}]},{"given":"Reyes","family":"Laguna","sequence":"additional","affiliation":[{"name":"Departamento de Farmacolog\u00eda, Farmacia y Tecnolog\u00eda Farmac\u00e9utica Universidade de Santiago de Compostela  15782 Santiago de Compostela Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3470-8299","authenticated-orcid":false,"given":"Maria J.","family":"Matos","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Org\u00e1nica Facultade de Farmacia Universidade de Santiago de Compostela  15782 Santiago de Compostela Spain"},{"name":"CIQUP\/Department of Chemistry and Biochemistry Faculty of Sciences University of Porto  4169-007 Porto Portugal"}]}],"member":"311","published-online":{"date-parts":[[2020,8,25]]},"reference":[{"key":"e_1_2_8_1_1","unstructured":"GBD 2016 Brain and Other CNS Cancer Collaborators Lancet Neurol.2019 18 376\u2013393."},{"key":"e_1_2_8_2_1","unstructured":"GBD 2016 Neurology Collaborators Lancet Neurol.2019 18 459\u2013480."},{"key":"e_1_2_8_3_1","unstructured":"GBD 2016 Dementia Collaborators Lancet Neurol.2019 18 88\u2013106."},{"key":"e_1_2_8_4_1","first-page":"2327","volume":"18","author":"Delogu G.","year":"2018","journal-title":"Curr. 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