{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T02:10:38Z","timestamp":1783649438459,"version":"3.55.0"},"reference-count":81,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T00:00:00Z","timestamp":1770163200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Unione Europea\u2013NextGenerationEU","award":["737\/2021"],"award-info":[{"award-number":["737\/2021"]}]},{"name":"Unione Europea\u2013NextGenerationEU","award":["FAR 2022 PNR"],"award-info":[{"award-number":["FAR 2022 PNR"]}]},{"name":"Ministry of Health, Italian National Institute of Health","award":["FAR25"],"award-info":[{"award-number":["FAR25"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>This paper reports the synthesis, structural characterization, and biological evaluation of a novel series of CuI and CuII complexes supported by an amantadine-functionalized bis(pyrazol-1-yl)acetate ligand (LAd) as potential anticancer agents for the treatment of glioblastoma (GBM). Comprehensive spectroscopic and structural investigations, including SR-XPS, XANES\/EXAFS, and DFT modeling, confirmed the successful coordination of LAd to copper centers in both oxidation states, affording well-defined molecular architectures with distinct coordination geometries. Among the synthesized compounds, the CuI complexes bearing triphenylphosphine co-ligands (compounds 4 and 5) exhibited the strongest cytotoxicity against U87 MG and LN18 GBM cell lines, showing IC50 values lower than those of cisplatin. These complexes induced a pronounced redox imbalance through reactive oxygen species (ROS) overproduction and glutathione (GSH) depletion, leading to G2\/M cell cycle arrest and cell death. Flow cytometry and Western blot analyses demonstrated that cell death occurs via caspase-dependent apoptosis in LN18 cells, as evidenced by PARP cleavage, downregulation of Bcl-xL, release of cytochrome c, and mitochondrial translocation of Bax. Altogether, these findings highlight the potential of lipophilic amantadine-functionalized CuI complexes as promising anticancer candidates targeting glioma cells through mitochondrial dysfunction and redox-mediated pathways.<\/jats:p>","DOI":"10.3390\/ijms27031531","type":"journal-article","created":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T12:51:56Z","timestamp":1770209516000},"page":"1531","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Synthesis, Structural Studies, and Biological Evaluation of Copper(I) and Copper(II) Complexes Supported by Bis(pyrazol-1-yl)acetate Ligand Functionalized with Amantadine for the Treatment of Glioblastoma"],"prefix":"10.3390","volume":"27","author":[{"given":"Sofia","family":"Migani","sequence":"first","affiliation":[{"name":"School of Science and Technology, Chemistry Division, University of Camerino, via Madonna delle Carceri (ChIP), 62032 Camerino, 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