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This study presents a comprehensive evaluation of four newly synthesized 4-substituted 7-hydroxycoumarin derivatives\n                    <jats:bold>C1<\/jats:bold>\n                    \u2013\n                    <jats:bold>C4<\/jats:bold>\n                    , highlighting their combined antiproliferative, enzyme-inhibitory, and pharmacokinetic properties. The compounds were tested for their cytotoxic effects on A549 lung carcinoma cells and CCD-18Co fibroblasts, inhibition of topoisomerase I (Topo I), and binding interactions with human serum albumin (HSA). Derivatives\n                    <jats:bold>C1<\/jats:bold>\n                    ,\n                    <jats:bold>C2<\/jats:bold>\n                    , and\n                    <jats:bold>C4<\/jats:bold>\n                    showed selective suppression of A549 metabolic activity and proliferation, while exhibiting minimal toxicity toward non-cancerous fibroblasts. All compounds inhibited Topo I to varying degrees, with\n                    <jats:bold>C1<\/jats:bold>\n                    displaying the highest potency, indicating that specific hydroxyl group arrangements are crucial for enzyme inhibition. Fluorescence spectroscopy and molecular docking revealed moderate to high HSA affinity (10\n                    <jats:sup>4<\/jats:sup>\n                    \u201310\n                    <jats:sup>6<\/jats:sup>\n                    \u00a0M\n                    <jats:sup>\u22121<\/jats:sup>\n                    ) and predominantly single-site binding, supporting their favorable plasma transport potential. Thermodynamic analysis showed distinct interaction patterns:\n                    <jats:bold>C1<\/jats:bold>\n                    and\n                    <jats:bold>C2<\/jats:bold>\n                    formed complexes stabilized primarily by hydrogen bonds and van der Waals forces, whereas\n                    <jats:bold>C3<\/jats:bold>\n                    and\n                    <jats:bold>C4<\/jats:bold>\n                    interacted mainly through hydrophobic forces. Competitive displacement assays identified Sudlow site I as the principal binding region, although molecular docking studies also suggested the possible involvement of site III. Overall, this work introduces a novel series of coumarin derivatives with a clearly defined multitarget anticancer profile which combines selective cytotoxicity, effective Topo I inhibition, and strong pharmacokinetic characteristics, thereby underscoring the potential of these derivatives as lead structures for further anticancer drug development.\n                  <\/jats:p>","DOI":"10.1007\/s00210-026-05062-w","type":"journal-article","created":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T02:46:07Z","timestamp":1770864367000},"page":"10873-10892","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multitarget evaluation of 4-substituted 7-hydroxycoumarin derivatives: anticancer activity, topoisomerase I inhibition, and interaction with human serum albumin"],"prefix":"10.1007","volume":"399","author":[{"given":"Adri\u00e1n","family":"Guck\u00fd","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Majern\u00edk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sl\u00e1vka","family":"Hamu\u013eakov\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna E.","family":"Nowak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rastislav","family":"Jend\u017eelovsk\u00fd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Fedoro\u010dko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e1ria","family":"Ko\u017eurkov\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,12]]},"reference":[{"key":"5062_CR1","doi-asserted-by":"publisher","first-page":"108728","DOI":"10.1016\/j.bioorg.2025.108728","volume":"163","author":"MO Aboelez","year":"2025","unstructured":"Aboelez MO, El-Remaily MAEAAA, Kamel MS, Al Kamaly O, Fadaly WAA, Nemr MTM, Ezelarab HAA (2025) Novel 3,4-diaminothieno[2,3-b]thiophene-2,5-dicarbohydrazide-based scaffolds as EGFRWT, EGFRT790M, and tubulin polymerization inhibitors with anti-proliferative activity. 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