Comprehensive Investigation of Benzimidazolium Derivatives Through Synthesis, Characterization, Cytotoxicity Activity, Immunocytochemistry, and ADME and Toxicity Analyses
ChemistryOpen, cilt.15, sa.9, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 15 Sayı: 9
- Basım Tarihi: 2026
- Doi Numarası: 10.1002/open.70284
- Dergi Adı: ChemistryOpen
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Chemical Abstracts Core, Compendex, EMBASE, MEDLINE, Directory of Open Access Journals, Academic Search Ultimate (EBSCO), Materials Science & Engineering Collection (ProQuest), Technology Collection (ProQuest)
- Anahtar Kelimeler: ADME and toxicity, benzimidazole, caspase-3, cytotoxic activity, fluorescence images, PARP1
- Süleyman Demirel Üniversitesi Adresli: Evet
Özet
In this study, three novel benzimidazolium derivatives (2a–c) bearing 4-fluoro, 3-chloro, and 3-methoxy substituents were synthesized. Their structures were confirmed by 1H NMR, 13C NMR, and IR spectroscopy. The cytotoxic activities of 2a–c 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-MB-231, A549, and HepG2 cells, with 2b showing the strongest antiproliferative effect, particularly against MDA-MB-231 cells. All compounds demonstrated higher IC50 values in L929 cells, indicating a degree of selectivity toward cancer cells. Compound 2b was further evaluated by immunocytochemical staining in MDA-MB-231 cells, demonstrating cleaved caspase-3 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-egg model revealed that compound 2c has a particularly high potential for gastrointestinal absorption. In addition, none of the compounds were predicted to cross the blood–brain barrier, which limits their potential for direct effects on the central nervous system.