Toxicological profiling of a de novo synthesized benzimidazole derivative with potent and selective proapoptotic potentials against breast cancer

This study aimed to investigate the toxicological profile of 1-(6-(1H-benzo[d]imidazole-2-yl)-2-methylpyridin-3yl) ethanone (BMPE), both in vitro and in vivo. The proapoptotic/necrotic and cell cycle arrest potentials of BMPE were assessed in MCF-7 cell line. The in vivo toxicology was assessed in female Balb/c mice by repeated dosing of 5, 25, and 50 mg/kg for 21 consecutive days, then different biochemical, inflammatory, and oxidative markers were assessed in sera/tissue homogenates of treated animals. The new derivative showed a potent selective cytotoxicity against malignant cell lines with IC50 value 0.2 mu M/mL, while the cytotoxic effect on normal Wi-38 cells was observed at IC50 value 0.4 mu M/mL; i.e. twofold the effective anticancer dose. BMPE exhibited an early DNA fragmentation-derived cell apoptosis observed at the G0/G1 checkpoint. In vivo, BMPE was biochemically/ immunologically tolerable at a pharmacological dose range of 5-25 mg/kg, with no significant rates of mortality/morbidity and minimal-to-moderate histopathological alterations recorded. The new derivative represents an attractive therapeutic candidate for breast cancer, considering its noticeable modulatory effect on the oxidative-inflammatory axis that would relate to its potent antitumor effect.

Automated summary

This study investigated the toxicological profile of BMPE in both in vitro and in vivo settings. The results showed that BMPE exhibited selective cytotoxicity against malignant cells and induced early cell apoptosis. In vivo experiments demonstrated that BMPE had tolerable toxicity at certain doses, and it also showed a modulatory effect on the oxidative-inflammatory response.