{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:18:36Z","timestamp":1783037916683,"version":"3.54.6"},"reference-count":34,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Applied Toxicology"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    A Cu(II) complex derived from a pyrimidine with the isatin group was synthesized and tested for its cytotoxic effects on A549 lung cancer and MCF\u20107 breast cancer cell lines, as well as its effects on apoptosis\u2010associated cell death and cell cycle regulation in A549 cells. To evaluate cytotoxicity, MTT assays were performed at 24, 48, and 72\u2009h, and IC\n                    <jats:sub>50<\/jats:sub>\n                    values were computed using the four\u2010parameter logistic (4PL) model. Selectivity indices were determined using the human primary dermal fibroblast (HDFa) cell line, and apoptosis\u2010related cell death was preliminarily assessed by flow cytometry with Annexin V\/PI double staining. Cell cycle distribution was analyzed by propidium iodide staining. The Cu(II) complex showed time\u2010dependent cytotoxicity in both cancer cell lines. The IC\n                    <jats:sub>50<\/jats:sub>\n                    values for A549 cells were 31.20, 17.68, and 11.33\u2009\u03bcM at 24, 48, and 72\u2009h, whereas MCF\u20107 cells had values of 70.41, 32.58, and 23.34\u2009\u03bcM, showing increased sensitivity. Selectivity indices showed the compound was two to four times more selective against cancer cells than healthy cells. Flow cytometry analysis at the 48\u2010h IC\n                    <jats:sub>50<\/jats:sub>\n                    concentration revealed apoptosis\u2010associated cell death, with a combined early apoptotic, late apoptotic, and necrotic cell population of approximately 60%, including a substantial necrotic fraction, suggesting that cell death may involve mixed mechanisms at this concentration. Cell cycle analysis revealed significant accumulation in the G2\/M phase (26%\u2009\u00b1\u20092.3%,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001), consistent with cell cycle arrest. In conclusion, the synthesized Cu(II) complex demonstrated substantial cytotoxic activity, apoptosis\u2010associated cell death, and G2\/M phase arrest in A549 and MCF\u20107 cell lines, suggesting its potential as a candidate anticancer agent warranting further mechanistic investigation.\n                  <\/jats:p>","DOI":"10.1002\/jat.70334","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T23:45:27Z","timestamp":1783035927000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Synthesis, Cytotoxicity, and Apoptosis\u2010Associated Cell Death Activity of an Isatin\u2010Containing Pyrimidine\u2010Derived Cu(II) Complex"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0857-4872","authenticated-orcid":false,"given":"M\u00fcjgan Kesik","family":"Oktay","sequence":"first","affiliation":[{"name":"Department of Medical Services and Techniques, Suhut Health Services Vocational School Afyonkarahisar Health Sciences University  Afyonkarahisar T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cansu","family":"Topkaya","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science Mu\u011fla S\u0131tk\u0131 Kocman University  Mu\u011fla T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elif","family":"Ka\u011fa","sequence":"additional","affiliation":[{"name":"Department of Medical Services and Techniques, Suhut Health Services Vocational School Afyonkarahisar Health Sciences University  Afyonkarahisar T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5218-5199","authenticated-orcid":false,"given":"Yasin","family":"Eren","sequence":"additional","affiliation":[{"name":"Department of Medical Services and Techniques, Suhut Health Services Vocational School Afyonkarahisar Health Sciences University  Afyonkarahisar T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramazan","family":"G\u00fcp","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science Mu\u011fla S\u0131tk\u0131 Kocman University  Mu\u011fla T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,2]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00432\u2010024\u201005641\u20105"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.inoche.2020.108004"},{"key":"e_1_2_11_4_1","volume-title":"Medicinal Chemistry of Anticancer Drugs","author":"Avendano C.","year":"2008"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apenergy.2015.10.104"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21492"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpa.2007.11.01"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinorgbio.2005.03.013"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1039\/d1dt03749h"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1101\/pdb.prot087288"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1134\/S1063774513010173"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/slct.202203242"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpa.2012.01.013"},{"issue":"1","key":"e_1_2_11_14_1","first-page":"1","article-title":"Isatin Derivatives With Several Biological Activities","volume":"6","author":"Grewal A. 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