{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T06:38:03Z","timestamp":1762065483290,"version":"build-2065373602"},"reference-count":70,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,8,31]],"date-time":"2022-08-31T00:00:00Z","timestamp":1661904000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"PT national funds (FCT-MCTES, Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia and Minist\u00e9rio da Ci\u00eancia, Tecnologia e Ensino Superior)","award":["UIDB\/50006\/2020","UIDP\/50006\/2020","SFRH\/BD\/132551\/2017","DL 57\/2016"],"award-info":[{"award-number":["UIDB\/50006\/2020","UIDP\/50006\/2020","SFRH\/BD\/132551\/2017","DL 57\/2016"]}]},{"name":"FCT-MCTES","award":["UIDB\/50006\/2020","UIDP\/50006\/2020","SFRH\/BD\/132551\/2017","DL 57\/2016"],"award-info":[{"award-number":["UIDB\/50006\/2020","UIDP\/50006\/2020","SFRH\/BD\/132551\/2017","DL 57\/2016"]}]},{"name":"Norma Transit\u00f3ria","award":["UIDB\/50006\/2020","UIDP\/50006\/2020","SFRH\/BD\/132551\/2017","DL 57\/2016"],"award-info":[{"award-number":["UIDB\/50006\/2020","UIDP\/50006\/2020","SFRH\/BD\/132551\/2017","DL 57\/2016"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Future Pharmacology"],"abstract":"<jats:p>The search for alternative and effective therapies to fight cancer is one of the main goals of the pharmaceutical industry. Recently, ionic liquids (ILs) have emerged as potential therapeutic agents with antitumor properties. The goal of this study was to synthesize and evaluate the bioactivity of different ILs coupled with the active pharmaceutical ingredient (API) valproate (VPA) as an antitumor agent. The toxicity of the prepared ionic liquids was evaluated by the MTT cell metabolic assay in human neuroblastoma SH-SY5Y and human primary Gingival Fibroblast (GF) cell lines, in which they showed inhibitory effects during the study period. In addition, low cytotoxicity against GF cell lines was observed, suggesting that these compounds are not toxic to human cell lines. [C2OHDMiM][VPA] demonstrated an outstanding antitumor activity against SH-SY5Y and lower activity against the non-neoplastic GF line. The herein assessed compounds played an important role in the modulation of the signaling pathways involved in the cellular behavior. This work also highlights the potential of these ILs-API as possible antitumor agents.<\/jats:p>","DOI":"10.3390\/futurepharmacol2030022","type":"journal-article","created":{"date-parts":[[2022,8,31]],"date-time":"2022-08-31T23:53:21Z","timestamp":1661990001000},"page":"320-329","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Bioactivity of Ionic Liquids Based on Valproate in SH-SY5Y Human Neuroblastoma Cell Line"],"prefix":"10.3390","volume":"2","author":[{"given":"Ana Rita","family":"Dias","sequence":"first","affiliation":[{"name":"CISA, Chemical and Biomolecular Sciences, School of Health, Polytechnic Institute of Porto, 4200-072 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1761-117X","authenticated-orcid":false,"given":"Ricardo","family":"Ferraz","sequence":"additional","affiliation":[{"name":"CISA, Chemical and Biomolecular Sciences, School of Health, Polytechnic Institute of Porto, 4200-072 Porto, Portugal"},{"name":"LAQV-REQUIMTE, Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, 4169-007 Porto, Portugal"}]},{"given":"Jo\u00e3o","family":"Costa-Rodrigues","sequence":"additional","affiliation":[{"name":"CISA, Chemical and Biomolecular Sciences, School of Health, Polytechnic Institute of Porto, 4200-072 Porto, Portugal"},{"name":"School of Health, Polytechnic Institute of Viana do Castelo, 4900-347 Viana do Castelo, Portugal"},{"name":"i3S, Institute for Innovation and Health Research, University of Porto, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9395-3112","authenticated-orcid":false,"given":"Andreia F. M.","family":"Santos","sequence":"additional","affiliation":[{"name":"LAQV-REQUIMTE, Department of Chemistry, NOVA School of Science and Technology, NOVA University of Lisbon, 2829-516 Caparica, Portugal"}]},{"given":"Manuel L.","family":"Jacinto","sequence":"additional","affiliation":[{"name":"LAQV-REQUIMTE, Department of Chemistry, NOVA School of Science and Technology, NOVA University of Lisbon, 2829-516 Caparica, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9920-936X","authenticated-orcid":false,"given":"Cristina","family":"Prud\u00eancio","sequence":"additional","affiliation":[{"name":"CISA, Chemical and Biomolecular Sciences, School of Health, Polytechnic Institute of Porto, 4200-072 Porto, Portugal"},{"name":"i3S, Institute for Innovation and Health Research, University of Porto, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1515-4518","authenticated-orcid":false,"given":"Jo\u00e3o Paulo","family":"Noronha","sequence":"additional","affiliation":[{"name":"LAQV-REQUIMTE, Department of Chemistry, NOVA School of Science and Technology, NOVA University of Lisbon, 2829-516 Caparica, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2520-1151","authenticated-orcid":false,"given":"Luis C.","family":"Branco","sequence":"additional","affiliation":[{"name":"LAQV-REQUIMTE, Department of Chemistry, NOVA School of Science and Technology, NOVA University of Lisbon, 2829-516 Caparica, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8104-7008","authenticated-orcid":false,"given":"\u017deljko","family":"Petrovski","sequence":"additional","affiliation":[{"name":"LAQV-REQUIMTE, Department of Chemistry, NOVA School of Science and Technology, NOVA University of Lisbon, 2829-516 Caparica, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.molliq.2018.09.025","article-title":"Fundamental importance of ionic interactions in the liquid phase: A review of recent studies of ionic liquids in biomedical and pharmaceutical applications","volume":"272","author":"Egorova","year":"2018","journal-title":"J. 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