{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T19:42:54Z","timestamp":1768592574916,"version":"3.49.0"},"reference-count":50,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2015,7,31]],"date-time":"2015-07-31T00:00:00Z","timestamp":1438300800000},"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>Selenium is traditionally considered as an antioxidant element and selenium compounds are often discussed in the context of chemoprevention and therapy. Recent studies, however, have revealed a rather more colorful and diverse biological action of selenium-based compounds, including the modulation of the intracellular redox homeostasis and an often selective interference with regulatory cellular pathways. Our basic activity and mode of action studies with simple selenium and tellurium salts in different strains of Staphylococcus aureus (MRSA) and Saccharomyces cerevisiae indicate that such compounds are sometimes not particularly toxic on their own, yet enhance the antibacterial potential of known antibiotics, possibly via the bioreductive formation of insoluble elemental deposits. Whilst the selenium and tellurium compounds tested do not necessarily act via the generation of Reactive Oxygen Species (ROS), they seem to interfere with various cellular pathways, including a possible inhibition of the proteasome and hindrance of DNA repair. Here, organic selenides are considerably more active compared to simple salts. The interference of selenium (and tellurium) compounds with multiple targets could provide new avenues for  the development of effective antibiotic and anticancer agents which may go well beyond the traditional notion of selenium as a simple antioxidant.<\/jats:p>","DOI":"10.3390\/molecules200813894","type":"journal-article","created":{"date-parts":[[2015,7,31]],"date-time":"2015-07-31T10:12:24Z","timestamp":1438337544000},"page":"13894-13912","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Aspects of a Distinct Cytotoxicity of Selenium Salts and Organic Selenides in Living Cells with Possible Implications for  Drug Design"],"prefix":"10.3390","volume":"20","author":[{"given":"Ethiene","family":"Estevam","sequence":"first","affiliation":[{"name":"Bioorganic Chemistry, Department of Pharmacy, Saarland University, Campus B2 1,  Saarbruecken D-66123, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karolina","family":"Witek","sequence":"additional","affiliation":[{"name":"Department of Technology and Biotechnology of Drugs, Faculty of Pharmacy,  Jagiellonian University-Medical College, ul. Medyczna 9, Cracow 30-688, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Faulstich","sequence":"additional","affiliation":[{"name":"Bioorganic Chemistry, Department of Pharmacy, Saarland University, Campus B2 1,  Saarbruecken D-66123, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2911-2607","authenticated-orcid":false,"given":"Muhammad","family":"Nasim","sequence":"additional","affiliation":[{"name":"Bioorganic Chemistry, Department of Pharmacy, Saarland University, Campus B2 1,  Saarbruecken D-66123, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gniewomir","family":"Latacz","sequence":"additional","affiliation":[{"name":"Department of Technology and Biotechnology of Drugs, Faculty of Pharmacy,  Jagiellonian University-Medical College, ul. Medyczna 9, Cracow 30-688, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enrique","family":"Dom\u00ednguez-\u00c1lvarez","sequence":"additional","affiliation":[{"name":"Department of Technology and Biotechnology of Drugs, Faculty of Pharmacy,  Jagiellonian University-Medical College, ul. Medyczna 9, Cracow 30-688, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katarzyna","family":"Kie\u0107-Kononowicz","sequence":"additional","affiliation":[{"name":"Department of Technology and Biotechnology of Drugs, Faculty of Pharmacy,  Jagiellonian University-Medical College, ul. Medyczna 9, Cracow 30-688, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marilene","family":"Demasi","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Bioqu\u00edmica e Biof\u00edsica, Instituto Butantan, S\u00e3o Paulo 05503-001, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jadwiga","family":"Handzlik","sequence":"additional","affiliation":[{"name":"Department of Technology and Biotechnology of Drugs, Faculty of Pharmacy,  Jagiellonian University-Medical College, ul. Medyczna 9, Cracow 30-688, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claus","family":"Jacob","sequence":"additional","affiliation":[{"name":"Bioorganic Chemistry, Department of Pharmacy, Saarland University, Campus B2 1,  Saarbruecken D-66123, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2015,7,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1039\/C3MT00185G","article-title":"Selenium biochemistry and its role for human health","volume":"6","author":"Roman","year":"2014","journal-title":"Metallomics"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.jinorgbio.2014.12.020","article-title":"Sulfur and selenium antioxidants: Challenging radical scavenging mechanisms and developing structure-activity relationships based on metal binding","volume":"145","author":"Zimmerman","year":"2015","journal-title":"J. Inorg. Biochem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"12258","DOI":"10.3390\/molecules190812258","article-title":"Intracellular Diagnostics: Hunting for the Mode of Action of Redox-Modulating Selenium Compounds in Selected Model Systems","volume":"19","author":"Manikova","year":"2014","journal-title":"Molecules"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1080\/10590501.2013.844757","article-title":"Friend or Foe? The Current Epidemiologic Evidence on Selenium and Human Cancer Risk","volume":"31","author":"Vinceti","year":"2013","journal-title":"J. Environ. Sci. Heal. C"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"4753","DOI":"10.1039\/b907831b","article-title":"Exploring synthetic avenues for the effective synthesis of selenium- and tellurium-containing multifunctional redox agents","volume":"7","author":"Mecklenburg","year":"2009","journal-title":"Org. Biomol. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"4203","DOI":"10.1039\/c0ob00086h","article-title":"Tellurium: an element with great biological potency and potential","volume":"8","author":"Ba","year":"2010","journal-title":"Org. Biomol. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"6954","DOI":"10.1021\/jm100576z","article-title":"Synthesis and Selective Anticancer Activity of Organochalcogen Based Redox Catalysts","volume":"53","author":"Doering","year":"2010","journal-title":"J. Med. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2021","DOI":"10.1016\/S0006-2952(03)00544-6","article-title":"Targeting oxidative stress-related diseases: Organochalcogen catalysts as redox sensitizers","volume":"66","author":"Giles","year":"2003","journal-title":"Biochem. Pharmacol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Giles, G.I., Giles, N.M., Collins, C.A., Holt, K., Fry, F.H., Lowden, P.A. S., Gutowski, N.J., and Jacob, C. (2003). Electrochemical, in vitro and cell culture analysis of integrated redox catalysts: implications for cancer therapy. Chem. Commun., 2030\u20132031.","DOI":"10.1039\/b302877a"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1042\/BST0391247","article-title":"Redox signalling via the cellular thiolstat","volume":"39","author":"Jacob","year":"2011","journal-title":"Biochem. Soc. Trans."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.cbpa.2010.10.015","article-title":"Redox active secondary metabolites","volume":"15","author":"Jacob","year":"2011","journal-title":"Curr. Opin. Chem. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Molina-Quiroz, R.C., Loyola, D.E., Munoz-Villagran, C.M., Quatrini, R., Vasquez, C.C., and Perez-Donoso, J.M. (2013). DNA, Cell Wall and General Oxidative Damage Underlie the Tellurite\/Cefotaxime Synergistic Effect in Escherichia coli. PLos ONE, 8.","DOI":"10.1371\/journal.pone.0079499"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.4014\/jmb.1105.05038","article-title":"Selenite Stress Elicits Physiological Adaptations in Bacillus sp. (Strain JS-2)","volume":"21","author":"Dhanjal","year":"2011","journal-title":"J. Microbiol. Biotechnol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1128\/jb.167.2.492-495.1986","article-title":"Penicillin-Binding Site on the Escherichia coli Cell-Envelope","volume":"167","author":"Amaral","year":"1986","journal-title":"J. Bacteriol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1385\/BTER:85:3:241","article-title":"Reactive oxygen species from mitochondria mediate SW480 cells apoptosis induced by Na2SeO3","volume":"85","author":"Wang","year":"2002","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1089\/152308603322110850","article-title":"Selenite activates caspase-independent necrotic cell death in Jurkat T cells and J774.2 macrophages by affecting mitochondrial oxidant generation","volume":"5","author":"Shilo","year":"2003","journal-title":"Antioxid. Redox Signal."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1038\/emm.2004.22","article-title":"Involvement of ROS and JNK1 in selenite-induced apoptosis in Chang liver cells","volume":"36","author":"Kim","year":"2004","journal-title":"Exp. Mol. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1620","DOI":"10.1016\/j.freeradbiomed.2011.03.006","article-title":"Interaction of selenite and tellurite with thiol-dependent redox enzymes: Kinetics and mitochondrial implications","volume":"50","author":"Rigobello","year":"2011","journal-title":"Free Radic. Biol. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"8759","DOI":"10.1074\/jbc.M610078200","article-title":"Extracellular production of hydrogen selenide accounts for thiol-assisted toxicity of selenite against Saccharomyces cerevisiae","volume":"282","author":"Tarze","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1039\/c3mt20205d","article-title":"Selenite and tellurite form mixed seleno- and tellurotrisulfides with CstR from Staphylococcus aureus","volume":"5","author":"Luebke","year":"2013","journal-title":"Metallomics"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Perez, J.M., Calderon, I.L., Arenas, F.A., Fuentes, D.E., Pradenas, G.A., Fuentes, E.L., Sandoval, J.M., Castro, M.E., Elias, A.O., and Vasquez, C.C. (2007). Bacterial Toxicity of Potassium Tellurite: Unveiling an Ancient Enigma. PLos ONE, 2.","DOI":"10.1371\/journal.pone.0000211"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1042\/BST0391221","article-title":"Oxidative chemistry of fluorescent dyes: Implications in the detection of reactive oxygen and nitrogen species","volume":"39","author":"Kalyanaraman","year":"2011","journal-title":"Biochem. Soc. Trans."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1480","DOI":"10.1002\/btpr.1992","article-title":"In vivo Synthesis of Selenium Nanoparticles by Halococcus salifodinae BK18 and their Anti-Proliferative Properties Against HeLa Cell Line","volume":"30","author":"Srivastava","year":"2014","journal-title":"Biotechnol. Progr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1007\/s00248-014-0429-y","article-title":"Reduction of Selenite by Azospirillum brasilense with the Formation of Selenium Nanoparticles","volume":"68","author":"Tugarova","year":"2014","journal-title":"Microb. Ecol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Yazdi, M.H., Mahdavi, M., Setayesh, N., Esfandyar, M., and Shahverdi, A.R. (2013). Selenium nanoparticle-enriched Lactobacillus brevis causes more efficient immune responses in vivo and reduces the liver metastasis in metastatic form of mouse breast cancer. Daru, 21.","DOI":"10.1186\/2008-2231-21-33"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Dhanjal, S., and Cameotra, S.S. (2010). Aerobic biogenesis of selenium nanospheres by Bacillus cereus isolated from coalmine soil. Microb. Cell Fact., 9.","DOI":"10.1186\/1475-2859-9-52"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"13480","DOI":"10.1073\/pnas.1105959108","article-title":"A bacterial process for selenium nanosphere assembly","volume":"108","author":"Debieux","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1016\/j.jbiosc.2013.10.010","article-title":"Isolation of a selenite-reducing and cadmium-resistant bacterium Pseudomonas sp. strain RB for microbial synthesis of CdSe nanoparticles","volume":"117","author":"Ayano","year":"2014","journal-title":"J. Biosci. Bioeng."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1099\/00207713-49-3-1177","article-title":"Sulfurospirillum barnesii sp. nov. and Sulfurospirillum arsenophilum sp. nov., new members of the Sulfurospirillum clade of the epsilon Proteobacteria","volume":"49","author":"Stolz","year":"1999","journal-title":"Int. J. Syst. Bacteriol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.jtemb.2014.11.003","article-title":"Selenite-Stress selected mutant strains of probiotic bacteria for Se source production","volume":"30","author":"Pusztahelyi","year":"2015","journal-title":"J. Trace Elem. Med. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1007\/s00792-009-0257-z","article-title":"Enrichment and isolation of Bacillus beveridgei sp nov., a facultative anaerobic haloalkaliphile from Mono Lake, California, that respires oxyanions of tellurium, selenium, and arsenic","volume":"13","author":"Baesman","year":"2009","journal-title":"Extremophiles"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.jhazmat.2013.12.028","article-title":"Reduction of chalcogen oxyanions and generation of nanoprecipitates by the photosynthetic bacterium Rhodobacter capsulatus","volume":"269","author":"Borghese","year":"2014","journal-title":"J. Hazard. Mater."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1099\/00221287-143-4-1181","article-title":"Tellurite reductase activity of nitrate reductase is responsible for the basal resistance of Escherichia coli to tellurite","volume":"143","author":"Avazeri","year":"1997","journal-title":"Microbiology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1021\/bi00867a039","article-title":"Enzymic Synthesis of Dimethyl Selenide from Sodium Selenite in Mouse Liver Extracts","volume":"5","author":"Ganther","year":"1966","journal-title":"Biochemistry"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/S0021-9258(18)73377-2","article-title":"The excretion of volatile selenium compounds after the administration of sodium selenite to white rats","volume":"133","author":"Schultz","year":"1940","journal-title":"J. Biol. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1166\/jbn.2011.1293","article-title":"Selective Antimicrobial Activity Associated with Sulfur Nanoparticles","volume":"7","author":"Schneider","year":"2011","journal-title":"J. Biomed. Nanotechnol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"8030","DOI":"10.1016\/S0021-9258(18)42403-9","article-title":"Selenodiglutathione Is a Highly Efficient Oxidant of Reduced Thioredoxin and a Substrate for Mammalian Thioredoxin Reductase","volume":"267","author":"Bjornstedt","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"27280","DOI":"10.1074\/jbc.271.44.27280","article-title":"Selective inhibitors of the proteasome-dependent and vacuolar pathways of protein degradation in Saccharomyces cerevisiae","volume":"271","author":"Lee","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.bbamcr.2013.03.022","article-title":"Pupylation as a signal for proteasomal degradation in bacteria","volume":"1843","author":"Striebel","year":"2014","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1016\/j.resmic.2009.08.017","article-title":"Proteases in bacterial pathogenesis","volume":"160","author":"Ingmer","year":"2009","journal-title":"Res. Microbiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1038\/nrd3846","article-title":"Bacterial proteolytic complexes as therapeutic targets","volume":"11","author":"Raju","year":"2012","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1854","DOI":"10.1128\/AAC.05131-11","article-title":"Pharmacological Inhibition of the ClpXP Protease Increases Bacterial Susceptibility to Host Cathelicidin Antimicrobial Peptides and Cell Envelope-Active Antibiotics","volume":"56","author":"McGillivray","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.abb.2010.06.009","article-title":"Fellutamide B is a potent inhibitor of the Mycobacterium tuberculosis proteasome","volume":"501","author":"Lin","year":"2010","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"10577","DOI":"10.1016\/j.tet.2012.09.021","article-title":"Selenium- and tellurium-containing redox modulators with distinct activity against macrophages: possible implications for the treatment of inflammatory diseases","volume":"68","author":"Doering","year":"2012","journal-title":"Tetrahedron"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"10920","DOI":"10.1002\/chem.201000884","article-title":"Selenium- and Tellurium-Containing Multifunctional Redox Agents as Biochemical Redox Modulators with Selective Cytotoxicity","volume":"16","author":"Jamier","year":"2010","journal-title":"Chemistry"},{"key":"ref_46","unstructured":"Shaaban, S. (2010). Synthesis and Biological Activity of Multifunctional Sensor\/Effector Catalysts. [Ph.D. Thesis, University of Saarland]."},{"key":"ref_47","unstructured":"Bhasin, A.K.K. (2014). Synthesis and Elucidation of Biochemical Mode of Action of Organoselenium Compounds Against Cancer. [Ph.D. Thesis, University of Saarland]."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.fob.2014.01.002","article-title":"Ebselen induces reactive oxygen species (ROS)-mediated cytotoxicity in Saccharomyces cerevisiae with inhibition of glutamate dehydrogenase being a target","volume":"4","author":"Azad","year":"2014","journal-title":"FEBS Open Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mrfmmm.2007.08.009","article-title":"Toxicity and mutagenicity of selenium compounds in Saccharomyces cerevisiae","volume":"638","author":"Letavayova","year":"2008","journal-title":"Mutat. Res. -Fund. Mol. Mech. Mutagen."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Kheradmand, E., Rafii, F., Yazdi, M.H., Sepahi, A.A., Shahverdi, A.R., and Oveisi, M.R. (2014). The antimicrobial effects of selenium nanoparticle-enriched probiotics and their fermented broth against Candida albicans. Daru, 22.","DOI":"10.1186\/2008-2231-22-48"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/20\/8\/13894\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T20:50:00Z","timestamp":1760215800000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/20\/8\/13894"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,7,31]]},"references-count":50,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2015,8]]}},"alternative-id":["molecules200813894"],"URL":"https:\/\/doi.org\/10.3390\/molecules200813894","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,7,31]]}}}