{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T13:38:07Z","timestamp":1773927487417,"version":"3.50.1"},"reference-count":31,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T00:00:00Z","timestamp":1744329600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Despite the wealth of data related to the advantages of formulating a wide range of compounds as salts to ameliorate their biological properties, there is scant information regarding the therapeutic potential of selenium (Se) salts. In this work, we have formulated six antibiotics as hydroselenite salts in order to compare their in vitro antibacterial and anticancer effects and evaluate if this approach could enhance their water solubility. In this regard, in almost all the cases, their solubility was increased by one order of magnitude. All the compounds were screened against a panel of three Gram-positive and three Gram-negative bacteria. Likewise, their antiproliferative activity was evaluated in breast, prostate, glioblastoma, and pancreatic cancer cell lines. Normal human dermal fibroblasts (NHDF) were used to determine their selectivity indexes (SI). Additionally, these novel hydroselenite salts were submitted to the National Cancer Institute (NCI) to study their antitumoral potential. Compounds SLT-2 and SLT-6 showed potent cytotoxicity against the glioblastoma cancer cell line, and their ability to induce apoptosis and reactive oxygen species (ROS) was further assessed. To conclude, we have demonstrated that the formulation of several antibiotics as hydroselenite salts could be a feasible approach to obtain biologically active compounds with an enhanced effect.<\/jats:p>","DOI":"10.3390\/molecules30081714","type":"journal-article","created":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T05:38:26Z","timestamp":1744349906000},"page":"1714","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Selenium in Action: Exploring the Biological Wonders of Hydroselenite Salts"],"prefix":"10.3390","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3088-4751","authenticated-orcid":false,"given":"Cristina","family":"Mor\u00e1n-Serradilla","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, Universidad de Navarra, 31008 Pamplona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8266-0445","authenticated-orcid":false,"given":"Daniel","family":"Plano","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Universidad de Navarra, 31008 Pamplona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5998-7298","authenticated-orcid":false,"given":"Yadira","family":"Pastor","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Parasitology, University of Navarra, 31008 Pamplona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1863-0580","authenticated-orcid":false,"given":"I\u00f1igo","family":"Navarro-Blasco","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Universidad de Navarra, 31008 Pamplona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5716-7202","authenticated-orcid":false,"given":"Asif","family":"Raza","sequence":"additional","affiliation":[{"name":"Department of Molecular and Precision Medicine, Penn State Cancer Institute, Penn State College of Medicine, 500 University Drive, Hershey, PA 17033, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arun K.","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Molecular and Precision Medicine, Penn State Cancer Institute, Penn State College of Medicine, 500 University Drive, Hershey, PA 17033, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3431-7826","authenticated-orcid":false,"given":"Carmen","family":"Sanmart\u00edn","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Universidad de Navarra, 31008 Pamplona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17","DOI":"10.3322\/caac.21763","article-title":"Cancer statistics, 2023","volume":"73","author":"Siegel","year":"2023","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.drup.2016.07.001","article-title":"Old drugs, novel ways out: Drug resistance toward cytotoxic chemotherapeutics","volume":"28","author":"Wijdeven","year":"2016","journal-title":"Drug Resist. Update"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Ajulo, S., and Awosile, B. (2024). Global antimicrobial resistance and use surveillance system (GLASS 2022): Investigating the relationship between antimicrobial resistance and antimicrobial consumption data across the participating countries. PLoS ONE, 19.","DOI":"10.1371\/journal.pone.0297921"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Mor\u00e1n-Serradilla, C., Angulo-Elizari, E., Henriquez-Figuereo, A., Sanmart\u00edn, C., Sharma, A.K., and Plano, D. (2022). Seleno-Metabolites and Their Precursors: A New Dawn for Several Illnesses?. Metabolites, 12.","DOI":"10.3390\/metabo12090874"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Kim, S.J., Choi, M.C., Park, J.M., and Chung, A.S. (2021). Antitumor Effects of Selenium. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222111844"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Rataan, A.O., Geary, S.M., Zakharia, Y., Rustum, Y.M., and Salem, A.K. (2022). Potential Role of Selenium in the Treatment of Cancer and Viral Infections. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23042215"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"7759","DOI":"10.1021\/acs.jmedchem.3c02426","article-title":"Selenization of Small Molecule Drugs: A New Player on the Board","volume":"67","author":"Plano","year":"2024","journal-title":"J. Med. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.molstruc.2015.10.029","article-title":"Novel perchlorate and phosphate salts of vinpocetine: Characterization, relative solid-state stability evaluation and Hirshfeld surface analysis","volume":"1105","author":"Ma","year":"2016","journal-title":"J. Mol. Struct."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"187","DOI":"10.3998\/ark.5550190.p008.244","article-title":"Novel quinazoline and pyrido [2,3-d]pyrimidine derivatives and their hydroselenite salts as antitumoral agents","volume":"2014","author":"Palopa","year":"2013","journal-title":"ARKIVOC"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1211\/jpp.61.03.0001","article-title":"Drug substances presented as sulfonic acid salts: Overview of utility, safety and regulation","volume":"61","author":"Elder","year":"2009","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"14271","DOI":"10.1039\/D0CC06653B","article-title":"Polyselenonium salts: Synthesis through sequential selenium-epoxy \u2018click\u2019 chemistry and Se-alkylation","volume":"56","author":"Eom","year":"2020","journal-title":"Chem. Commun."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4975","DOI":"10.1021\/acsapm.3c02928","article-title":"High-Efficiency Bactericidal and Biofilm Elimination Ability of the Biodegradable Alternating Sequence Main-Chain Polyselenium Salt","volume":"6","author":"Dai","year":"2024","journal-title":"ACS Appl. Polym. Mater."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1021\/acsmacrolett.2c00537","article-title":"Degradable Selenium-Containing Polymers for Low Cytotoxic Antibacterial Materials","volume":"11","author":"Li","year":"2022","journal-title":"ACS Macro Lett."},{"key":"ref_14","first-page":"67","article-title":"Synthesis and Antibacterial Activity of Selenium-functionalized Poly(\u03b5-caprolactone)","volume":"40","author":"Li","year":"2022","journal-title":"CJPS"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"10489","DOI":"10.1016\/j.tet.2012.06.076","article-title":"Generation and characterization of aliphatic selenothioic acid salts","volume":"68","author":"Murai","year":"2012","journal-title":"Tetrahedron"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Makrecka-Kuka, M., Dimitrijevs, P., Domracheva, I., Jaudzems, K., Dambrova, M., and Arsenyan, P. (2020). Fused isoselenazolium salts suppress breast cancer cell growth by dramatic increase in pyruvate-dependent mitochondrial ROS production. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-78620-8"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Witek, K., Nasim, M.J., Bischoff, M., Gaupp, R., Arsenyan, P., Vasiljeva, J., Mar\u0107, M.A., Olejarz, A., Latacz, G., and Kie\u0107-Kononowicz, K. (2017). Selenazolinium Salts as \u201cSmall Molecule Catalysts\u201d with High Potency against ESKAPE Bacterial Pathogens. Molecules, 22.","DOI":"10.3390\/molecules22122174"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1002\/aoc.530","article-title":"Synthesis and cytotoxicity of silylalkylthio-substituted N-heterocycles and their hydroselenites","volume":"17","author":"Arsenyan","year":"2003","journal-title":"Appl. Organomet. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1002\/aoc.277","article-title":"Amino-acid hydroselenites: Synthesis and cytotoxicity","volume":"16","author":"Lukevics","year":"2002","journal-title":"Appl. Organomet. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Ramos-Inza, S., Henriquez-Figuereo, A., Moreno, E., Berzosa, M., Enc\u00edo, I., Plano, D., and Sanmart\u00edn, C. (2022). Unveiling a New Selenocyanate as a Multitarget Candidate with Anticancer, Antileishmanial and Antibacterial Potential. Molecules, 27.","DOI":"10.3390\/molecules27217477"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Ramos-Inza, S., Aliaga, C., Enc\u00edo, I., Raza, A., Sharma, A.K., Aydillo, C., Mart\u00ednez-S\u00e1ez, N., Sanmart\u00edn, C., and Plano, D. (2023). First Generation of Antioxidant Precursors for Bioisosteric Se-NSAIDs: Design, Synthesis, and In Vitro and In Vivo Anticancer Evaluation. Antioxidants, 12.","DOI":"10.2139\/ssrn.4395287"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Cao, L., Zhang, J., Du, Y., Sun, M., Xiang, Y., Sheng, Y., Ren, X., and Shao, J. (2021). Selenite induced breast cancer MCF7 cells apoptosis through endoplasmic reticulum stress and oxidative stress pathway. Chem.-Biol. Interact., 349.","DOI":"10.1016\/j.cbi.2021.109651"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1016\/j.bbrc.2011.04.109","article-title":"Combined effect of sodium selenite and docetaxel on PC3 metastatic prostate cancer cell line","volume":"408","author":"Freitas","year":"2011","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"6314","DOI":"10.1158\/0008-5472.CAN-06-4217","article-title":"Sodium Selenite Induces Superoxide-Mediated Mitochondrial Damage and Subsequent Autophagic Cell Death in Malignant Glioma Cells","volume":"67","author":"Kim","year":"2007","journal-title":"Cancer Res."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Doello, K., Mesas, C., Qui\u00f1onero, F., Perazzoli, G., Cabeza, L., Prados, J., Melguizo, C., and Ortiz, R. (2021). The Antitumor Activity of Sodium Selenite Alone and in Combination with Gemcitabine in Pancreatic Cancer: An In Vitro and In Vivo Study. Cancers, 13.","DOI":"10.3390\/cancers13133169"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Fan, T.W., El-Amouri, S.S., Macedo, J.K.A., Wang, Q.J., Song, H., Cassel, T., and Lane, A.N. (2018). Stable Isotope-Resolved Metabolomics Shows Metabolic Resistance to Anti-Cancer Selenite in 3D Spheroids versus 2D Cell Cultures. Metabolites, 8.","DOI":"10.3390\/metabo8030040"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Strober, W. (2015). Trypan Blue Exclusion Test of Cell Viability. Curr. Protoc. Immunol., 111.","DOI":"10.1002\/0471142735.ima03bs111"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"AN20110014","DOI":"10.1042\/AN20110014","article-title":"Current Review of in Vivo GBM Rodent Models: Emphasis on the CNS-1 Tumour Model","volume":"3","author":"Jacobs","year":"2011","journal-title":"ASN Neuro"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"114839","DOI":"10.1016\/j.ejmech.2022.114839","article-title":"Design, synthesis and anticancer evaluation of novel Se-NSAID hybrid molecules: Identification of a Se-indomethacin analog as a potential therapeutic for breast cancer","volume":"244","author":"Raza","year":"2022","journal-title":"Eur. J. Med. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3536","DOI":"10.3390\/nu7053536","article-title":"Redox-active selenium compounds\u2014From toxicity and cell death to cancer treatment","volume":"7","author":"Misra","year":"2015","journal-title":"Nutrients"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.trac.2012.02.007","article-title":"Quantitative 1H NMR spectroscopy","volume":"35","author":"Bharti","year":"2012","journal-title":"TrAC Trends Anal. Chem."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/30\/8\/1714\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:12:43Z","timestamp":1760029963000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/30\/8\/1714"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,11]]},"references-count":31,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["molecules30081714"],"URL":"https:\/\/doi.org\/10.3390\/molecules30081714","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,11]]}}}