{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T11:55:40Z","timestamp":1786449340860,"version":"build-2736575974"},"reference-count":78,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T00:00:00Z","timestamp":1757462400000},"content-version":"vor","delay-in-days":9,"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":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Through applying the hybridization technique, new coumarin derivatives (\n                    <jats:bold>2\u201317<\/jats:bold>\n                    ) were prepared with substitution at coumarin C\u20103 utilizing various heterocyclic derivatives, aiming to afford multi\u2010target carbonic anhydrases (CAs) IX\/XII and topoisomerase II (Topo II) inhibitors with potent antiproliferative activity. Eight different cell lines were used to evaluate the growth inhibition percentages (GI%) of cancer cells determined by coumarin analogues\n                    <jats:bold>1\u201317<\/jats:bold>\n                    . Analogues\n                    <jats:bold>16<\/jats:bold>\n                    and\n                    <jats:bold>17<\/jats:bold>\n                    had the most substantial cytotoxic effects, achieving mean GI% of 86.59% and 85.74%, respectively, exceeding doxorubicin (Dox), which demonstrated a mean GI% of 69.15. Furthermore, the CAs IX\/XII and Topo II inhibitory potentials for compound\n                    <jats:bold>17<\/jats:bold>\n                    were evaluated according to the protein expression analysis in the MG\u201063 cancer cells. Analogue\n                    <jats:bold>17<\/jats:bold>\n                    downregulated the expression of CA IX, CA XII, and Topo II proteins by 0.43\u2010, 0.51\u2010, and 0.56\u2010fold change, respectively, indicating frontier inhibitory potentials. Additionally, analogue\n                    <jats:bold>17<\/jats:bold>\n                    achieved upregulation of apoptotic proteins (Caspases 3, 7, and 9, and BAX by 1.52\u2010, 3.10\u2010, 1.67\u2010, and 1.90\u2010fold change, respectively). On the contrary, compound\n                    <jats:bold>17<\/jats:bold>\n                    induced downregulation of the antiapoptotic proteins BCL\u20102, MMP2, and MMP9 by 0.44\u2010, 0.38\u2010, and 0.45\u2010fold change, respectively. Besides, compound\n                    <jats:bold>17<\/jats:bold>\n                    achieved an arrest at the G0\u2013G1 phase of the cell cycle and elevated the cellular levels from 65.75% of the control cells to 92.54%. Finally, three molecular docking processes of the superior analogue\n                    <jats:bold>17<\/jats:bold>\n                    toward CA IX, CA XII, and Topo II targets were performed to investigate its molecular interactions.\n                  <\/jats:p>","DOI":"10.1002\/ardp.70094","type":"journal-article","created":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T05:56:44Z","timestamp":1757570204000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Design and Synthesis of New Multi\u2010Target Coumarin Analogues Acting as Carbonic Anhydrases IX\/XII and Topoisomerase II Inhibitors With Apoptotic Potential"],"prefix":"10.1002","volume":"358","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8173-6073","authenticated-orcid":false,"given":"Ahmed A.","family":"Al\u2010Karmalawy","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy The University of Mashreq Baghdad Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3039-7646","authenticated-orcid":false,"given":"Tarek A.","family":"Yousef","sequence":"additional","affiliation":[{"name":"College of Science, Chemistry Department Imam Mohammad Ibn Saud Islamic University (IMSIU) Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2188-0647","authenticated-orcid":false,"given":"Ali Khalil","family":"Ali","sequence":"additional","affiliation":[{"name":"Chemistry Department, Faculty of Science Ain Shams University Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed A.","family":"Zeidan","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy Horus University\u2010Egypt New Damietta 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