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We postulated that the appropriate alteration of the azole pharmacophore through the inclusion of a 1,2,3-triazole ring might result in dual-acting drugs that preserve antifungal efficacy while exhibiting anticancer properties. In accordance with the aforementioned reasoning, a targeted library of oxiconazole-derived 1,2,3-triazoles was synthesized and assessed for antifungal potency, cytotoxicity, and mechanism of action. Different analogues (\n                    <jats:bold>4<\/jats:bold>\n                    ,\n                    <jats:bold>5b, 6, 8, 10, 11, 18,<\/jats:bold>\n                    and\n                    <jats:bold>19c<\/jats:bold>\n                    ) exhibited significant antifungal activity against fluconazole-sensitive C.\n                    <jats:italic>albicans<\/jats:italic>\n                    strains (S1, S2), with minimum inhibitory concentrations (MICs) ranging from 16 to 64 \u03bcg\/mL, while reduced activity was observed against resistant strains (S3, S4). Compound\n                    <jats:bold>11<\/jats:bold>\n                    , the nearest structural counterpart of oxiconazole, proved to be the most powerful alternative, markedly suppressing ergosterol biosynthesis in both susceptible (S1) and resistant (S3) strains by 65.65% and 61.89%, respectively. Checkerboard assays demonstrated additive to indifferent relationships between\n                    <jats:bold>11<\/jats:bold>\n                    and fluconazole, with fractional inhibitory concentration index (FICI) values of 2 and 0.75 against S1 and S3, respectively. Docking study revealed that\n                    <jats:bold>11<\/jats:bold>\n                    occupied the lanosterol 14\u03b1-demethylase active pocket. In addition,\u00a0compounds (\n                    <jats:bold>5b, 5c, 7\u20139, 11, 13, 16, 17<\/jats:bold>\n                    , and\n                    <jats:bold>19c<\/jats:bold>\n                    ) had moderate to modest cytotoxic activity against A549, Caco-2, and MCF7\u00a0cancer cells, with IC\n                    <jats:sub>50<\/jats:sub>\n                    values of 33.66 to 100 \u00b5M in comparison to docetaxel. Compounds (\n                    <jats:bold>7, 8,<\/jats:bold>\n                    and\n                    <jats:bold>11<\/jats:bold>\n                    ) were particularly active, with compound\n                    <jats:bold>11<\/jats:bold>\n                    triggering S-phase cell-cycle arrest and apoptosis in A549 cells.\n                    <jats:bold>11<\/jats:bold>\n                    , a chemo sensitizing adjuvant, significantly lowered the IC\n                    <jats:sub>50<\/jats:sub>\n                    of docetaxel in A549 and Caco-2 cells by 87.98% and 43.35%, respectively. Combination index (CI) analysis revealed strong synergism (CI\u2009=\u20090.16) in A549 cells and moderate synergism (CI\u2009=\u20090.58) in Caco-2 cells at the 50% effect level (Fa\u2009=\u20090.5), confirming that the combination is more effective than either agent alone. Overall, these data indicate compound\n                    <jats:bold>11<\/jats:bold>\n                    as a mechanistically validated dual antifungal-anticancer lead that bridges azole optimization and adjuvant oncology methods, necessitating further structure\u2013activity optimization and in vivo testing.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-65234-9","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T09:04:11Z","timestamp":1786698251000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Design, synthesis, molecular modelling and biological evaluation of oxiconazole-based 1,2,3-triazoles as dually acting antifungal and antitumor agents"],"prefix":"10.1038","volume":"16","author":[{"given":"Azza E.","family":"Ismail","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed I.","family":"Ashmawy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael G.","family":"Shehat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mustafa A.","family":"Al-Seqely","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mona H.","family":"Badr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherif A. 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