本研究旨在探究1-(6-(1H-苯并[d]咪唑-2-基)-2-甲基吡啶-3-基)乙酮（BMPE）的体外和体内毒理学特征。本研究评估了BMPE在MCF-7细胞系中的促细胞凋亡/坏死和细胞周期阻滞潜力。通过连续21天对雌性Balb/c小鼠进行5、25和50 mg/kg的重复剂量给药，并评估了受处理动物的血清/组织均匀物中的不同生化、炎症和氧化标志物。新的衍生物对恶性细胞系表现出强烈的选择性细胞毒性，其IC50值为0.2 μM/mL，而对正常Wi-38细胞的细胞毒性效应在IC50值0.4 μM/mL时观察到，即有效的抗癌剂量的两倍。BMPE在G0/G1检查点观察到早期的DNA断裂相关的细胞凋亡。体内，BMPE在5-25 mg/kg的药理剂量范围内在生化学/免疫学上可耐受，在记录的死亡率/病死率没有显著的情况下，记录了轻度至中度的组织病理学改变。考虑到其对氧化炎症轴的显著调节作用与其强效抗肿瘤作用有关，该新衍生物是乳腺癌的有吸引力的治疗候选药物。版权所有 © 2023. 由爱思唯尔出版。

This study aimed to investigate the toxicological profile of 1-(6-(1H-benzo[d]imidazole-2-yl)-2-methylpyridin-3-yl) 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 μM/mL, while the cytotoxic effect on normal Wi-38 cells was observed at IC50 value 0.4 μM/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.Copyright © 2023. Published by Elsevier Ltd.