{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T15:53:14Z","timestamp":1791561194501,"version":"4.3.4"},"reference-count":82,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:00:00Z","timestamp":1791504000000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Cancer remains one of the leading causes of mortality worldwide, highlighting the need for novel anticancer agents with improved efficacy and selectivity. In this study, a series of chalcone derivatives bearing phenylpiperazine, 2\u2010fluorophenylpiperazine, and morpholine moieties (\n                    <jats:bold>1a\u2013g<\/jats:bold>\n                    ,\n                    <jats:bold>2a\u2013g<\/jats:bold>\n                    , and\n                    <jats:bold>3a\u2013g<\/jats:bold>\n                    ) were designed, synthesized, and evaluated for their anticancer potential. The target compounds were synthesized via Claisen\u2013Schmidt condensation under basic conditions and characterized by\n                    <jats:sup>1<\/jats:sup>\n                    H NMR,\n                    <jats:sup>13<\/jats:sup>\n                    C NMR, and elemental analysis. Their cytotoxic activities were assessed against PC\u20103, PANC\u20101, A549, and MCF\u20107 cancer cell lines using the MTT assay, with HEK\u2010293 cells serving as a non\u2010cancerous control. Most compounds exhibited notable antiproliferative activity and favorable selectivity compared with doxorubicin, cisplatin, and gemcitabine. Among the tested cell lines, A549 cells were the most sensitive. Compounds\n                    <jats:bold>2d<\/jats:bold>\n                    ,\n                    <jats:bold>2b<\/jats:bold>\n                    ,\n                    <jats:bold>2c<\/jats:bold>\n                    ,\n                    <jats:bold>2e<\/jats:bold>\n                    ,\n                    <jats:bold>2g<\/jats:bold>\n                    , and\n                    <jats:bold>2a<\/jats:bold>\n                    showed particularly potent activity against A549 cells, with IC\n                    <jats:sub>50<\/jats:sub>\n                    values of 5.35\u2009\u00b1\u20090.08, 5.71\u2009\u00b1\u20090.09, 5.95\u2009\u00b1\u20090.09, 5.83\u2009\u00b1\u20090.09, 5.94\u2009\u00b1\u20090.09, and 5.96\u2009\u00b1\u20090.09\u2009\u00b5M, respectively. Notably,\n                    <jats:bold>2c<\/jats:bold>\n                    exhibited the highest selectivity toward A549 cells (SI\u2009=\u20093.26). SAR analysis indicated that the 2\u2010fluorophenylpiperazine moiety enhanced anticancer activity, while halogen substitution generally improved potency and selectivity. Induced Fit Docking and Glide XP simulations supported these findings, suggesting that\n                    <jats:bold>2d<\/jats:bold>\n                    and\n                    <jats:bold>2c<\/jats:bold>\n                    achieve their activity through key hinge\u2010region anchoring and isoform\u2010specific interactions with PI3K\u2010\u03b1 and PI3K\u2010\u03b3. Overall, these findings identify fluorinated chalcone derivatives, particularly\n                    <jats:bold>2d<\/jats:bold>\n                    , as promising leads for further anticancer drug development.\n                  <\/jats:p>","DOI":"10.1002\/ardp.70357","type":"journal-article","created":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T15:18:16Z","timestamp":1791559096000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Design, Synthesis, and Anticancer Evaluation of Novel Chalcone Derivatives Bearing Piperazine and Morpholine Moieties"],"prefix":"10.1002","volume":"359","author":[{"given":"Nedime","family":"\u00c7al\u0131\u015fkan","sequence":"first","affiliation":[{"name":"Department of Chemistry, Faculty of Art and Sciences Recep Tayyip Erdogan University Rize 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Rize Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3408-8202","authenticated-orcid":false,"given":"Emre","family":"Mente\u015fe","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Art and Sciences Recep Tayyip Erdogan University Rize 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