{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T09:04:13Z","timestamp":1789981453728,"version":"4.0.1"},"reference-count":46,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"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":["ChemistryOpen"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:p>\n                    In this study, three novel benzimidazolium derivatives (\n                    <jats:bold>2a\u2013c<\/jats:bold>\n                    ) bearing 4\u2010fluoro, 3\u2010chloro, and 3\u2010methoxy substituents were synthesized. Their structures were confirmed by\n                    <jats:sup>1<\/jats:sup>\n                    H NMR,\n                    <jats:sup>13<\/jats:sup>\n                    C NMR, and IR spectroscopy. The cytotoxic activities of\n                    <jats:bold>2a\u2013c<\/jats:bold>\n                    were evaluated against human breast, lung, and liver cancer cell lines, as well as mouse fibroblast (L929) cells. All compounds exhibited cytotoxic activity in MDA\u2010MB\u2010231, A549, and HepG2 cells, with\n                    <jats:bold>2b<\/jats:bold>\n                    showing the strongest antiproliferative effect, particularly against MDA\u2010MB\u2010231 cells. All compounds demonstrated higher IC\n                    <jats:sub>50<\/jats:sub>\n                    values in L929 cells, indicating a degree of selectivity toward cancer cells. Compound\n                    <jats:bold>2b<\/jats:bold>\n                    was further evaluated by immunocytochemical staining in MDA\u2010MB\u2010231 cells, demonstrating cleaved caspase\u20103 expression and PARP1 cleavage. Furthermore, the physicochemical, pharmacokinetic, and toxicity profiles of compounds were evaluated using in silico methods. The results indicated that the compounds possess high lipophilicity but show limited bioavailability due to low solubility. The boiled\u2010egg model revealed that compound\n                    <jats:bold>2c<\/jats:bold>\n                    has a particularly high potential for gastrointestinal absorption. In addition, none of the compounds were predicted to cross the blood\u2013brain barrier, which limits their potential for direct effects on the central nervous system.\n                  <\/jats:p>","DOI":"10.1002\/open.70284","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:37:22Z","timestamp":1787031442000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comprehensive Investigation of Benzimidazolium Derivatives Through Synthesis, Characterization, Cytotoxicity Activity, Immunocytochemistry, and ADME and Toxicity Analyses"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6562-2554","authenticated-orcid":false,"given":"Gulay","family":"Dilek","sequence":"first","affiliation":[{"name":"Department of Basic Pharmaceutical Sciences Faculty of Pharmacy Zonguldak Bulent Ecevit University  Zonguldak T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1260-9425","authenticated-orcid":false,"given":"Senem","family":"Akkoc","sequence":"additional","affiliation":[{"name":"Department of Basic Pharmaceutical Sciences Faculty of Pharmacy Suleyman Demirel University  Isparta T\u00fcrkiye"},{"name":"Faculty of Engineering and Natural Sciences Bah\u00e7e\u015fehir University  Istanbul T\u00fcrkiye"},{"name":"D\u2019Decus Cosmetics Industry and Trade Limited Company (Sue &amp; Larosel Brands)  Isparta 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