{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T04:25:15Z","timestamp":1780460715283,"version":"3.54.1"},"reference-count":18,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T00:00:00Z","timestamp":1749600000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Disulfiram (DSF), a well-known anti-alcoholism drug, exhibits potent anticancer activity via its metabolite, diethyldithiocarbamate (DDC), which forms a cytotoxic copper complex that selectively targets cancer stem cells. However, its clinical utility is limited by poor solubility and rapid plasma metabolism. This study explores saccharide-linked DDCs as novel prodrugs designed to enhance stability, solubility, and tumour-selective activation. These compounds feature thioglycosidic bonds that shield the DDC moiety from premature degradation while retaining its metal-chelating function to form the active copper(II)bis(N,N-diethyldithiocarbamate) (Cu(DDC)2) complex. The synthesised derivatives were characterised and evaluated for serum stability and in vitro cytotoxicity across several cancer cell lines, including colorectal, breast, lung, and brain cancers. Copper-complexed saccharide-DDC prodrugs demonstrated remarkable cytotoxicity, with improved biostability and solubility profiles. These findings highlight the potential of saccharide-linked DDCs as stable, copper-activated prodrugs for cancer therapy. Further in vivo studies are warranted to validate their pharmacokinetics and clinical relevance.<\/jats:p>","DOI":"10.3390\/ijms26125589","type":"journal-article","created":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T08:18:06Z","timestamp":1749629886000},"page":"5589","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Sugar-Linked Diethyldithiocarbamate Derivatives: A Novel Class of Anticancer Agents"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7670-2859","authenticated-orcid":false,"given":"Mohammad","family":"Najlah","sequence":"first","affiliation":[{"name":"Pharmaceutical Research Group, School of Allied Health, Faculty of Health, Education, Medicine and Social Care, Anglia Ruskin University, Bishops Hall Lane, Chelmsford CM1 1SQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niamh","family":"McCallum","sequence":"additional","affiliation":[{"name":"Pharmaceutical Research Group, School of Allied Health, Faculty of Health, Education, Medicine and Social Care, Anglia Ruskin University, Bishops Hall Lane, Chelmsford CM1 1SQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3829-242X","authenticated-orcid":false,"given":"Ana Maria","family":"Pereira","sequence":"additional","affiliation":[{"name":"Pharmaceutical Research Group, School of Allied Health, Faculty of Health, Education, Medicine and Social Care, Anglia Ruskin University, Bishops Hall Lane, Chelmsford CM1 1SQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Alves","sequence":"additional","affiliation":[{"name":"Pharmaceutical Research Group, School of Allied Health, Faculty of Health, Education, Medicine and Social Care, Anglia Ruskin University, Bishops Hall Lane, Chelmsford CM1 1SQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1931-534X","authenticated-orcid":false,"given":"Niusha","family":"Ansari-Fard","sequence":"additional","affiliation":[{"name":"Pharmaceutical Research Group, School of Allied Health, Faculty of Health, Education, Medicine and Social Care, Anglia Ruskin University, Bishops Hall Lane, Chelmsford CM1 1SQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7221-9878","authenticated-orcid":false,"given":"Sahrish","family":"Rehmani","sequence":"additional","affiliation":[{"name":"Pharmaceutical Research Group, School of Allied Health, Faculty of Health, Education, Medicine and Social Care, Anglia Ruskin University, Bishops Hall Lane, Chelmsford CM1 1SQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ay\u015fe","family":"Kaya","sequence":"additional","affiliation":[{"name":"Pharmaceutical Research Group, School of Allied Health, Faculty of Health, Education, Medicine and Social Care, Anglia Ruskin University, Bishops Hall Lane, Chelmsford CM1 1SQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21708","article-title":"Cancer statistics","volume":"72","author":"Siegel","year":"2022","journal-title":"CA Cancer J. 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Biomolecules, 14.","DOI":"10.3390\/biom14121651"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"6070","DOI":"10.1158\/1078-0432.CCR-09-1035","article-title":"High-throughput cell-based screening of 4910 known drugs and drug-like small molecules identifies disulfiram as an inhibitor of prostate cancer cell growth","volume":"15","author":"Iljin","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1038\/nature25016","article-title":"Alcohol-abuse drug disulfiram targets cancer via p97 segregase adaptor NPL4","volume":"552","author":"Skrott","year":"2017","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"13334","DOI":"10.1039\/C4CC04767B","article-title":"On the interaction of copper(II) with disulfiram","volume":"50","author":"Lewis","year":"2014","journal-title":"Chem. Comm."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4129","DOI":"10.2147\/IJN.S137347","article-title":"Development and optimization of an injectable formulation of copper diethyldithiocarbamate, an active anticancer agent","volume":"12","author":"Wehbe","year":"2017","journal-title":"Int. J. Nanomed."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Kannappan, V., Ali, M., Small, B., Rajendran, G., Elzhenni, S., Taj, H., Wang, W., and Dou, Q.P. (2021). Recent advances in repurposing disulfiram and disulfiram derivatives as copper-dependent anticancer agents. Front. Mol. Biosci., 8.","DOI":"10.3389\/fmolb.2021.741316"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1186\/s13643-021-01858-4","article-title":"Anticancer effects of disulfiram: A systematic review of in vitro, animal, and human studies","volume":"11","author":"Wang","year":"2022","journal-title":"Syst. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"6256","DOI":"10.1021\/jm8007807","article-title":"Ni(II), Cu(II), and Zn(II) diethyldithiocarbamate complexes show various activities against the proteasome in breast cancer cells","volume":"51","author":"Cvek","year":"2008","journal-title":"J. Med. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"6313","DOI":"10.1016\/j.bmcl.2009.09.095","article-title":"Synthesis of new sugar derivatives and evaluation of their antibacterial activities against Mycobacterium tuberculosis","volume":"19","author":"Horita","year":"2009","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3529","DOI":"10.1016\/j.tetlet.2016.06.106","article-title":"Protection-free synthesis of glycosyl dithiocarbamates in aqueous media by using 2-chloroimidazolinium reagent","volume":"57","author":"Li","year":"2016","journal-title":"Tetrahedron. Lett."},{"key":"ref_14","first-page":"279","article-title":"Drug delivery systems based on sugar-macromolecule conjugates","volume":"5","author":"Davis","year":"2002","journal-title":"Curr. Opin. Drug Discov. Dev."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"McCallum, N., and Najlah, M. (2024). The Anticancer Activity of Monosaccharides: Perspectives and Outlooks. Cancers, 16.","DOI":"10.3390\/cancers16162775"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"795","DOI":"10.3390\/polysaccharides2040048","article-title":"Using chitosan or chitosan derivatives in cancer therapy","volume":"2","author":"Shakil","year":"2021","journal-title":"Polysaccharides"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1038\/sj.bjc.6600547","article-title":"Evaluation of 2-deoxy-D-glucose as a chemotherapeutic agent: Mechanism of cell death","volume":"87","author":"Aft","year":"2002","journal-title":"Br. J. Cancer"},{"key":"ref_18","first-page":"1827","article-title":"Chemopreventive effects of dithiocarbamates on aflatoxin B1 metabolism and formation of AFB1 adducts with glutathione","volume":"18","author":"Gopalaswamy","year":"1998","journal-title":"Anticancer Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/12\/5589\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:50:02Z","timestamp":1760032202000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/12\/5589"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,11]]},"references-count":18,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["ijms26125589"],"URL":"https:\/\/doi.org\/10.3390\/ijms26125589","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,11]]}}}