{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T05:47:55Z","timestamp":1785736075999,"version":"3.56.0"},"reference-count":45,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2019,1,6]],"date-time":"2019-01-06T00:00:00Z","timestamp":1546732800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002850","name":"Fondo Nacional de Desarrollo Cient\u00edfico y Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["1170718"],"award-info":[{"award-number":["1170718"]}],"id":[{"id":"10.13039\/501100002850","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Ugi four component reaction (Ugi-4CR) isocyanide-based multicomponent reactions were used to synthesize diN-substituted glycyl-phenylalanine (diNsGF) derivatives. All of the synthesized compounds were characterized by spectroscopic and spectrometric techniques. In order to evaluate potential biological applications, the synthesized compounds were tested in computational models that predict the bioactivity of organic molecules by using only bi-dimensional molecular information. The diNsGF derivatives were predicted as cholinesterase inhibitors. Experimentally, all of the synthesized diNsGF derivatives showed moderate inhibitory activities against acetylcholinesterase (AChE) and poor activities against butyrylcholinesterase (BuChE). Compound 7a has significant activity and selectivity against AChE, which reveals that the diNsGF scaffold could be improved to reach novel candidates by combining other chemical components of the Ugi-4CR in a high-throughput combinatorial screening experiment. Molecular docking experiments of diNsGF derivatives inside AChE suggest that these compounds placed the phenylalanine group at the peripheral site of AChE. The orientations and chemical interactions of diNsGF derivatives were analyzed, and the changeable groups were identified for future exploration of novel candidates that could lead to the improvement of diNsGF derivative inhibitory activities.<\/jats:p>","DOI":"10.3390\/molecules24010189","type":"journal-article","created":{"date-parts":[[2019,1,9]],"date-time":"2019-01-09T03:06:06Z","timestamp":1547003166000},"page":"189","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Synthesis of diN-Substituted Glycyl-Phenylalanine Derivatives by Using Ugi Four Component Reaction and Their Potential as Acetylcholinesterase Inhibitors"],"prefix":"10.3390","volume":"24","author":[{"given":"Luis","family":"Prent-Pe\u00f1aloza","sequence":"first","affiliation":[{"name":"Organic Synthesis Laboratory and Biological Activity (LSO-Act-Bio), Institute of Chemistry of Natural Resources, Universidad de Talca, Casilla 747, Talca 3460000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4767-5868","authenticated-orcid":false,"given":"Alexander F.","family":"De la Torre","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Org\u00e1nica, Facultad de Ciencias Qu\u00edmicas, Universidad de Concepci\u00f3n, Concepci\u00f3n 4030000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4941-6619","authenticated-orcid":false,"given":"Jos\u00e9 L.","family":"Vel\u00e1zquez-Libera","sequence":"additional","affiliation":[{"name":"Centro de Bioinform\u00e1tica y Simulaci\u00f3n Molecular (CBSM), Universidad de Talca, Casilla 747, Talca 3460000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margarita","family":"Guti\u00e9rrez","sequence":"additional","affiliation":[{"name":"Organic Synthesis Laboratory and Biological Activity (LSO-Act-Bio), Institute of Chemistry of Natural Resources, Universidad de Talca, Casilla 747, Talca 3460000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0182-1444","authenticated-orcid":false,"given":"Julio","family":"Caballero","sequence":"additional","affiliation":[{"name":"Centro de Bioinform\u00e1tica y Simulaci\u00f3n Molecular (CBSM), Universidad de Talca, Casilla 747, Talca 3460000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,1,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1039\/c2md20089a","article-title":"Recent applications of multicomponent reactions in medicinal chemistry","volume":"3","author":"Slobbe","year":"2012","journal-title":"Med. 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