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Herein in vitro study investigates spirohydantoin derivatives with diversified dopamine D\n                    <jats:sub>2<\/jats:sub>\n                    R-like affinity as potential anti-glioblastoma agents. Cytotoxic studies with three human GBM cell lines (U87MG, A172 and U138MG) and human skin fibroblasts as non-tumor control, led to choose compounds\n                    <jats:bold>4<\/jats:bold>\n                    ,\n                    <jats:bold>6<\/jats:bold>\n                    and\n                    <jats:bold>7<\/jats:bold>\n                    with selective cell-damaging activity much greater than these observed for clinically used chemotherapeutic temozolomide (TMZ). The IC\n                    <jats:sub>50<\/jats:sub>\n                    values for A172 cells were 56, 5, 21 and 513 \u00b5M for\n                    <jats:bold>4<\/jats:bold>\n                    ,\n                    <jats:bold>6<\/jats:bold>\n                    ,\n                    <jats:bold>7<\/jats:bold>\n                    and TMZ, respectively. Moreover, we demonstrated the potency of\n                    <jats:bold>4<\/jats:bold>\n                    ,\n                    <jats:bold>6<\/jats:bold>\n                    and\n                    <jats:bold>7<\/jats:bold>\n                    as adjuvant therapeutics, even in GBM resistant phenotype. Interestingly, we observed a cell-damaging effect of calpain inhibitors in GBM cells and their higher cytotoxicity when combined with\n                    <jats:bold>4<\/jats:bold>\n                    ,\n                    <jats:bold>6<\/jats:bold>\n                    and\n                    <jats:bold>7<\/jats:bold>\n                    , which together with molecular docking studies suggest that tested hydantoins might be also calpain inhibitors. Comparing the IC\n                    <jats:sub>50<\/jats:sub>\n                    values between used GBM cell lines, dopamine receptors\u2019 affinities and associating these data with expression level of D\n                    <jats:sub>2<\/jats:sub>\n                    -like receptors, we rather exclude the involvement of these receptors in anticancer mechanism of investigated compounds. Collectively, these results justify further investigation of compounds from hydantoin family as anti-glioblastoma candidates.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-43014-9","type":"journal-article","created":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T19:15:16Z","timestamp":1774379716000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Spirohydantoin derivatives exert dopamine D2-like receptor-independent cytotoxicity in glioblastoma cells with possible involvement of calpain inhibition"],"prefix":"10.1038","volume":"16","author":[{"given":"Katarzyna","family":"Kucwaj-Brysz","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabina","family":"Podlewska","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Klaudia","family":"Jakubowska","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aleksandra","family":"M\u0105sior","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Micha\u0142","family":"Wilczkowski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beata","family":"Duszy\u0144ska","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justyna","family":"Druka\u0142a","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jadwiga","family":"Handzlik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danuta","family":"Jantas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,3,24]]},"reference":[{"key":"43014_CR1","doi-asserted-by":"publisher","first-page":"217601","DOI":"10.1016\/j.canlet.2025.217601","volume":"617","author":"M Rana","year":"2025","unstructured":"Rana, M., Liou, K. 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