{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T08:02:21Z","timestamp":1753862541599,"version":"3.41.2"},"reference-count":51,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T00:00:00Z","timestamp":1747872000000},"content-version":"vor","delay-in-days":21,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Based on the pharmacophore structural characteristics of topoisomerase II (TopoII) inhibitors: (i) planar polyaromatic skeleton; (ii) the cation core; (iii) a groove\u2010binding side chain moiety, 16 urolithin derivatives with <jats:italic>O<\/jats:italic>\u2010dialkylaminoalkyl substitutions were designed and synthesized. Most of the synthesized compounds showed improved TopoII\u03b1 inhibitory and antiproliferative activities. <jats:bold>20<\/jats:bold> with the best TopoII\u03b1 inhibitory activity also exhibited excellent antiproliferative activity with IC<jats:sub>50<\/jats:sub> values of 0.91\u2009\u00b1\u20090.01, 1.93\u2009\u00b1\u20090.04, and 2.84\u2009\u00b1\u20090.34\u2009\u03bcM against the MDA\u2010MB\u2010231, HeLa, and A549 cell lines, being about 12.55, 3.95, and 2.17 times more active than VP\u201016 (IC<jats:sub>50<\/jats:sub> 11.42\u2009\u00b1\u20090.82, 7.63\u2009\u00b1\u20090.46, and 6.15\u2009\u00b1\u20090.43\u2009\u03bcM, respectively). Meanwhile, <jats:bold>20<\/jats:bold> exhibited weak toxicity to normal cells. In addition, <jats:bold>20<\/jats:bold> exerted anti\u2010migration and anti\u2010invasion activity against MDA\u2010MB\u2010231 cells. Our results supported that <jats:bold>20<\/jats:bold> might act as TopoII\u03b1 inhibitor with the potential to become a new type of antitumor drug lead.<\/jats:p>","DOI":"10.1002\/ardp.70009","type":"journal-article","created":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T11:20:13Z","timestamp":1747912813000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Design and Synthesis of <i>O<\/i>\u2010Dialkylaminoalkyl Substituted Urolithin Derivatives: DNA Topoisomerase II\u03b1 Inhibition With Promising Antiproliferative Activity"],"prefix":"10.1002","volume":"358","author":[{"given":"Xintong","family":"Li","sequence":"first","affiliation":[{"name":"State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Department of Natural Products Chemistry, School of Pharmaceutical Sciences Shandong University Jinan 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Components in Traditional Chinese Medicine, Department of Natural Products Chemistry, School of Pharmaceutical Sciences Shandong University Jinan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuemao","family":"Shen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Department of Natural Products Chemistry, School of Pharmaceutical Sciences Shandong University Jinan 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