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Despite the effectiveness of traditional chemotherapeutic agents such as 5\u2010fluorouracil (5\u2010FU), their lack of selectivity often results in damage to healthy tissues, leading to undesirable adverse effects. The aim of this study was to modify 5\u2010FU with mannose containing 1,2,3\u2010triazole compound to reduce its toxic effect, and to investigate the anticancer properties of the resulting 5\u2010FU derivative (5\u2010FUD\u2010Man) in ER\u2010positive MCF\u20107 breast cancer cells. Our results demonstrated that while 5\u2010FU caused significant cytotoxicity in both cancerous and healthy cells, 5\u2010FUD\u2010Man showed selective cytotoxicity, with minimal effects on MCF\u201010A cells. Furthermore, immunofluorescence staining results indicated that 5\u2010FUD\u2010Man was more strongly activated apoptosis (Caspase\u20103, AIF), autophagy\u2010mediated (LC3B), and stress\u2010associated signaling pathways (ERK1\/2) in MCF\u20107 cells compared to 5\u2010FU. These findings suggest that the combined use of carbohydrate\u2010based targeting via mannose and a bioactive triazole compound may enhance the selectivity and therapeutic efficacy of 5\u2010FU\u2010based treatments in breast cancer. Overall, 5\u2010FUD\u2010Man appears to be a promising candidate for further development as a more targeted and potentially safer therapeutic strategy.<\/jats:p>","DOI":"10.1002\/jbt.70806","type":"journal-article","created":{"date-parts":[[2026,3,29]],"date-time":"2026-03-29T16:45:26Z","timestamp":1774802726000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Anti\u2010Cancer Effect of a New 5\u2010FU Derivative Containing Triazole\u2010Bearing Mannose (5\u2010FUD\u2010MAN) Against Human Breast Cancer Cells Through LC3B\u2010Mediated Cell Death"],"prefix":"10.1002","volume":"40","author":[{"given":"Ebru","family":"\u015eanci","sequence":"first","affiliation":[{"name":"Center for Drug Research &amp; Development and Pharmacokinetics Applications Ege University Izmir Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azada","family":"Aliyeva","sequence":"additional","affiliation":[{"name":"Faculty of Science, Department of Molecular Biology and Genetics Atat\u00fcrk University Erzurum Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Buket","family":"Bakan","sequence":"additional","affiliation":[{"name":"Faculty of Science, Department of Molecular Biology and Genetics Atat\u00fcrk University Erzurum Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mustafa","family":"\u00d6zkaraca","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary, Department of Pathology Cumhuriyet University Sivas Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erkan","family":"Halay","sequence":"additional","affiliation":[{"name":"Banaz Vocational School, Chemical Technology and Laboratory Technology Usak University Usak Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kadir","family":"Ay","sequence":"additional","affiliation":[{"name":"Faculty of Letter and Science, Department of Chemistry Manisa Celal Bayar University Manisa Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamer","family":"Karayildirim","sequence":"additional","affiliation":[{"name":"Faculty of Science, Department of Chemistry Ege University Izmir Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7483-0184","authenticated-orcid":false,"given":"N. 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