{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T08:01:26Z","timestamp":1774339286454,"version":"3.50.1"},"reference-count":73,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,8,9]],"date-time":"2021-08-09T00:00:00Z","timestamp":1628467200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010198","name":"Ministerio de Econom\u00eda, Industria y Competitividad, Gobierno de Espa\u00f1a","doi-asserted-by":"publisher","award":["RTI2018-101818-B-I00"],"award-info":[{"award-number":["RTI2018-101818-B-I00"]}],"id":[{"id":"10.13039\/501100010198","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003086","name":"Eusko Jaurlaritza","doi-asserted-by":"publisher","award":["IT 992-16"],"award-info":[{"award-number":["IT 992-16"]}],"id":[{"id":"10.13039\/501100003086","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003451","name":"Euskal Herriko Unibertsitatea","doi-asserted-by":"publisher","award":["ESPDOC19\/47"],"award-info":[{"award-number":["ESPDOC19\/47"]}],"id":[{"id":"10.13039\/501100003451","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003451","name":"Euskal Herriko Unibertsitatea","doi-asserted-by":"publisher","award":["PIF17\/79"],"award-info":[{"award-number":["PIF17\/79"]}],"id":[{"id":"10.13039\/501100003451","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>An efficient synthetic methodology for the preparation of 3-amino 1,5-dihydro-2H-pyrrol-2-ones through a multicomponent reaction of amines, aldehydes, and pyruvate derivatives is reported. In addition, the densely substituted lactam substrates show in vitro cytotoxicity, inhibiting the growth of carcinoma human tumor cell lines HEK293 (human embryonic kidney), MCF7 (human breast adenocarcinoma), HTB81 (human prostate carcinoma), HeLa (human epithelioid cervix carcinoma), RKO (human colon epithelial carcinoma), SKOV3 (human ovarian carcinoma), and A549 (carcinomic human alveolar basal epithelial cell). Given the possibilities in the diversity of the substituents that offer the multicomponent synthetic methodology, an extensive structure-activity profile is presented. In addition, both enantiomers of phosphonate-derived \u03b3-lactam have been synthesized and isolated and a study of the cytotoxic activity of the racemic substrate vs. its two enantiomers is also presented. Cell morphology analysis and flow cytometry assays indicate that the main pathway by which our compounds induce cytotoxicity is based on the activation of the intracellular apoptotic mechanism.<\/jats:p>","DOI":"10.3390\/ph14080782","type":"journal-article","created":{"date-parts":[[2021,8,9]],"date-time":"2021-08-09T05:17:06Z","timestamp":1628486226000},"page":"782","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["A Multicomponent Protocol for the Synthesis of Highly Functionalized \u03b3-Lactam Derivatives and Their Applications as Antiproliferative Agents"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6973-0912","authenticated-orcid":false,"given":"Xabier","family":"del Corte","sequence":"first","affiliation":[{"name":"Departamento de Qu\u00edmica Org\u00e1nica I, Centro de Investigaci\u00f3n y Estudios Avanzados \u201cLucio Lascaray\u201d-Facultad de Farmacia, 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de la Universidad 7, 01006 Vitoria-Gasteiz, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3738-7611","authenticated-orcid":false,"given":"Ilia","family":"Villate-Beitia","sequence":"additional","affiliation":[{"name":"NanoBioCel Group, Facultad de Farmacia, University of the Basque Country (UPV\/EHU), 01006 Vitoria-Gasteiz, Spain"},{"name":"Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Facultad de Farmacia, University of the Basque Country (UPV\/EHU), 01006 Vitoria-Gasteiz, Spain"},{"name":"Bioaraba, NanoBioCel Research Group, Facultad de Farmacia, University of the Basque Country (UPV\/EHU), 01006 Vitoria-Gasteiz, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Myriam","family":"Sainz-Ramos","sequence":"additional","affiliation":[{"name":"NanoBioCel Group, Facultad de Farmacia, University of the Basque Country (UPV\/EHU), 01006 Vitoria-Gasteiz, Spain"},{"name":"Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Facultad de Farmacia, University of the Basque Country (UPV\/EHU), 01006 Vitoria-Gasteiz, Spain"},{"name":"Bioaraba, NanoBioCel Research Group, Facultad de Farmacia, University of the Basque Country (UPV\/EHU), 01006 Vitoria-Gasteiz, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1167-0240","authenticated-orcid":false,"given":"Edorta","family":"Mart\u00ednez de Marigorta","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Org\u00e1nica I, Centro de Investigaci\u00f3n y Estudios Avanzados \u201cLucio Lascaray\u201d-Facultad de Farmacia, University of the Basque Country (UPV\/EHU), Paseo de la Universidad 7, 01006 Vitoria-Gasteiz, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3938-2267","authenticated-orcid":false,"given":"Jos\u00e9 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