{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T12:48:26Z","timestamp":1791377306207,"version":"4.3.2"},"reference-count":25,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2026,4,14]]},"abstract":"<jats:p>\n                    Monastrol, a DHPM\u2010based Eg5 inhibitor with well\u2010known antiproliferative activity but limited therapeutic potential due to poor solubility and low bioavailability, was selected as the lead compound for the design of styryl\u2010modified 3,4\u2010dihydropyrimidin\u20102(1\n                    <jats:italic>H<\/jats:italic>\n                    )\u2010ones with an improved pharmaceutical profile. Twelve derivatives (\n                    <jats:bold>10\u201321<\/jats:bold>\n                    ) were synthesized via the Biginelli reaction and evaluated for cytotoxicity in HeLa and MCF\u20107 cells. Styryl derivatives\n                    <jats:bold>16<\/jats:bold>\n                    and\n                    <jats:bold>17<\/jats:bold>\n                    emerged as the most active. In HeLa cells, derivatives\n                    <jats:bold>17<\/jats:bold>\n                    (IC50\u2009=\u20091.3\u2009\u00b5M) and\n                    <jats:bold>16<\/jats:bold>\n                    (IC50\u2009=\u20093.7\u2009\u00b5M) were approximately 85\u2010fold and 30\u2010fold more potent than monastrol (IC50\u2009=\u2009111\u2009\u00b5M), respectively. In MCF\u20107 cells, derivatives\n                    <jats:bold>16<\/jats:bold>\n                    and\n                    <jats:bold>17<\/jats:bold>\n                    displayed 18\u2010 to 20\u2010fold higher potency than monastrol, respectively. Biological results also indicate that styryl derivatives\n                    <jats:bold>16<\/jats:bold>\n                    and\n                    <jats:bold>17<\/jats:bold>\n                    induce apoptosis in both HeLa and MCF\u20107 cells. In HeLa cells, activation of caspase\u20108, \u20109, and \u20103 suggests the involvement of both intrinsic and extrinsic pathways. In contrast, in MCF\u20107 cells, the increased expression of p53 and p21, together with PARP cleavage, suggests a p53\u2010dependent apoptotic response. Derivatives\n                    <jats:bold>16<\/jats:bold>\n                    and\n                    <jats:bold>17<\/jats:bold>\n                    emerged as promising Eg5 inhibitors from docking studies, but their poor aqueous solubility (0.2\u20130.7\u2009\u00b5M), despite high biological stability, highlights the need for formulation strategies to improve drug\u2010like properties.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.202501073","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T19:26:47Z","timestamp":1775590007000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Development of Styryl\u2010Modified 3,4\u2010Dihydropyrimidin\u20102(1\n                    <i>H<\/i>\n                    )\u2010ones as Potential Antitumor Agents"],"prefix":"10.1002","volume":"21","author":[{"given":"Konstantinos","family":"Panagoulias","sequence":"first","affiliation":[{"name":"Laboratory of Organic Chemistry Department of Chemistry National and Kapodistrian University of Athens  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woonghee","family":"Kim","sequence":"additional","affiliation":[{"name":"Science for Life Laboratory KTH\u2010Royal Institute of Technology  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murat","family":"Ozdemir","sequence":"additional","affiliation":[{"name":"Trustlife Laboratories Drug Research &amp; Development Center  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Busra","family":"Turan","sequence":"additional","affiliation":[{"name":"Trustlife Laboratories Drug Research &amp; Development Center  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adil","family":"Mardinoglu","sequence":"additional","affiliation":[{"name":"Science for Life Laboratory KTH\u2010Royal Institute of Technology  Stockholm Sweden"},{"name":"Centre for Host\u2010Microbiome Interactions Faculty of Dentistry, Oral &amp; Craniofacial Sciences King's College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hasan","family":"Turkez","sequence":"additional","affiliation":[{"name":"Department of Medical Biology Faculty of Medicine Atat\u00fcrk University  Erzurum Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Trisciuzzi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Pharmaceutical Sciences University of Bari \u201cAldo Moro\u201d  Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orazio","family":"Nicolotti","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Pharmaceutical Sciences University of Bari \u201cAldo Moro\u201d  Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Di Stefano","sequence":"additional","affiliation":[{"name":"Department of Pharmacy \u201cG. D\u2019Annunzio\u201d University of Chieti\u2010Pescara  Chieti Scalo (Chieti) Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0734-6579","authenticated-orcid":false,"given":"Stamatia","family":"Vassiliou","sequence":"additional","affiliation":[{"name":"Laboratory of Organic Chemistry Department of Chemistry National and Kapodistrian University of Athens  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6253-0443","authenticated-orcid":false,"given":"Ivana","family":"Cacciatore","sequence":"additional","affiliation":[{"name":"Department of Pharmacy \u201cG. 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