{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T16:33:23Z","timestamp":1789662803590,"version":"4.0.1"},"reference-count":25,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100020595","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["MOST 109\u20102320\u2010B\u2010039\u2010024"],"award-info":[{"award-number":["MOST 109\u20102320\u2010B\u2010039\u2010024"]}],"id":[{"id":"10.13039\/100020595","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020595","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["MOST 111\u20102320\u2010B\u2010039\u2010047\u2010MY3"],"award-info":[{"award-number":["MOST 111\u20102320\u2010B\u2010039\u2010047\u2010MY3"]}],"id":[{"id":"10.13039\/100020595","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020595","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["MOST 110\u20102320\u2010B\u2010182\u2010023\u2010MY3"],"award-info":[{"award-number":["MOST 110\u20102320\u2010B\u2010182\u2010023\u2010MY3"]}],"id":[{"id":"10.13039\/100020595","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007300","name":"China Medical University","doi-asserted-by":"publisher","award":["CMU113\u2010MF\u201035"],"award-info":[{"award-number":["CMU113\u2010MF\u201035"]}],"id":[{"id":"10.13039\/501100007300","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Quinazolin\u20104\u2010one scaffolds offer rich anticancer chemistry but often trade potency for selectivity. Building on a tubulin\u2010targeting lead (\n                    <jats:bold>MJ\u201065<\/jats:bold>\n                    ), 12 new derivatives (\n                    <jats:bold>26<\/jats:bold>\n                    \u2013\n                    <jats:bold>37<\/jats:bold>\n                    ) were synthesized to dissect geometry\u2013activity relationships and enhance the polarity of C2\u2010substituents. Cytotoxicity was profiled against cancerous (HCT116 and CAL27) and normal (FHC) cells.\n                    <jats:italic>In silico<\/jats:italic>\n                    studies employed CDOCKER against tubulin (PDB 5NJH), GROMACS for molecular dynamics (MD), and ProTox\u20103.0 for toxicity estimation. The previously synthesized geometry\u2010matched pairs\n                    <jats:bold>21<\/jats:bold>\n                    \u2013\n                    <jats:bold>25<\/jats:bold>\n                    were active at 10\u2009\u03bcM. In contrast, their isomers\n                    <jats:bold>26<\/jats:bold>\n                    \u2013\n                    <jats:bold>30<\/jats:bold>\n                    were largely inactive, revealing a configuration\u2010dependent binding mechanism. Optimizing polarity yielded\n                    <jats:bold>Holu\u20107<\/jats:bold>\n                    (compound\n                    <jats:bold>35<\/jats:bold>\n                    ; 2,4\u2010dihydroxyphenyl at the C2\u2010position), which exhibited sub\u201050\u2009nM IC\n                    <jats:sub>50<\/jats:sub>\n                    in HCT116\/CAL27 cells and &gt;\u200910\u2009\u03bcM in FHC cells and induced robust G\n                    <jats:sub>2<\/jats:sub>\n                    \/M arrest. Docking\/MD supported stable vinca\u2010site engagement, with hydrogen bonds to ASP179\/ASN206 and \u03c0\u2010stacking with TYR224. ProTox\u20103.0 predicted a higher LD\n                    <jats:sub>50<\/jats:sub>\n                    and absence of major organ toxicities relative to\n                    <jats:bold>MJ\u201065<\/jats:bold>\n                    . This data indicates that configuration\u2010aware, polarity\u2010tuned design can deliver selective quinazolinone anticancer candidates; therefore,\n                    <jats:bold>Holu\u20107<\/jats:bold>\n                    merits further preclinical evaluation.\n                  <\/jats:p>","DOI":"10.1111\/cbdd.70209","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T12:31:24Z","timestamp":1764937884000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Design and Synthesis of Holu\u20107, a Quinazolinone Derivative With an Active Stereo Geometry and Polar 2,4\u2010Dihydroxyphenyl Group, as a Selective Anticancer Agent"],"prefix":"10.1111","volume":"106","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1064-3216","authenticated-orcid":false,"given":"Kuo\u2010Chu","family":"Lai","sequence":"first","affiliation":[{"name":"Department of Physiology and Pharmacology, College of Medicine Chang Gung University  Taoyuan City Taiwan, ROC"},{"name":"Division of Hematology\u2013Oncology, Department of Internal Medicine Chang Gung Memorial Hospital, Linkou Medical Center  Taoyuan City Taiwan, ROC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0874-195X","authenticated-orcid":false,"given":"Hui\u2010Hsia","family":"Hsieh","sequence":"additional","affiliation":[{"name":"School of Pharmacy China Medical University  Taichung City Taiwan, ROC"},{"name":"Department of Pharmacy, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation  Taichung City Taiwan, ROC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi\u2010Liang","family":"Lu","sequence":"additional","affiliation":[{"name":"School of Pharmacy China Medical University  Taichung City Taiwan, ROC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1015-6503","authenticated-orcid":false,"given":"Shin\u2010Yi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Imaging and Radiological Science China Medical University  Taichung City Taiwan, ROC"},{"name":"Graduate Institute of Biomedical Sciences China Medical University  Taichung City Taiwan, ROC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4252-2128","authenticated-orcid":false,"given":"Hai\u2010Anh","family":"Ha","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy Da Nang University of Medical Technology and Pharmacy  Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6714-8788","authenticated-orcid":false,"given":"Mann\u2010Jen","family":"Hour","sequence":"additional","affiliation":[{"name":"School of Pharmacy China Medical 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