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Thirty\u2010seven derivatives were obtained through lipase catalysis in mild reaction conditions with good to excellent yields and a reduced environmental impact. The scope of the reaction was explored in terms of enzyme source, solvent, temperature, substrate\u2010to\u2010nucleophile and enzyme\u2010to\u2010substrate ratios, and substrate versatility. Ten representative derivatives were evaluated as potential anti\u2010Alzheimer's disease (AD) agents using\n                    <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                    models. Among them, octyl 3\u2010(1\n                    <jats:italic>H<\/jats:italic>\n                    \u2010indol\u20103\u2010yl)propanoate (\n                    <jats:bold>6e<\/jats:bold>\n                    ),\n                    <jats:italic>N<\/jats:italic>\n                    \u2010butyl\u20103\u2010(1\n                    <jats:italic>H<\/jats:italic>\n                    \u2010indol\u20103\u2010yl)propanamide (\n                    <jats:bold>10a<\/jats:bold>\n                    ), and (\n                    <jats:italic>S<\/jats:italic>\n                    )\u2010\n                    <jats:italic>N<\/jats:italic>\n                    \u2010(2\u2010hydroxypropyl)\u20103\u2010(1\n                    <jats:italic>H<\/jats:italic>\n                    \u2010indol\u20103\u2010yl)propanamide (\n                    <jats:bold>13c<\/jats:bold>\n                    ) emerged as the most promising candidates, demonstrating significant improvements in AD pathology, including enhanced locomotion and mitochondrial function. In addition, the obtained compounds showed no toxicity in Vero cells, making them potential lead drug candidates.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.70395","type":"journal-article","created":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T02:38:30Z","timestamp":1784947110000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sustainable Synthesis of 3\u2010(1\n                    <i>H<\/i>\n                    \u2010Indol\u20103\u2010yl)propionic Acid Derivatives with Anti\u2010Alzheimer Activity"],"prefix":"10.1002","volume":"21","author":[{"given":"Fabricio","family":"Freije Garc\u00eda","sequence":"first","affiliation":[{"name":"Laboratorio de Biocat\u00e1lisis Departamento de Qu\u00edmica Org\u00e1nica y UMYMFOR Facultad de Ciencias Exactas y Naturales Universidad de Buenos Aires Ciudad Universitaria  Buenos Aires 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