鉴于胃癌的恶性程度，开发高效、低毒的靶向药物对于延长患者生存和改善患者预后至关重要。在本研究中，我们基于苯并咪唑支架进行了结构优化。值得注意的是，化合物 8 f 在 MGC803 细胞中表现出最有效的抗增殖活性，并诱导细胞周期停滞在 G0/G1 期。进一步的机制研究表明，化合物8 f通过提高细胞内活性氧（ROS）水平并激活丝裂原激活蛋白激酶（MAPK）信号通路，并伴随相应的标记物变化，引起MGC803细胞凋亡。体内研究还验证了化合物8 f对带有MGC803细胞的异种移植模型中的肿瘤生长的抑制作用，且没有明显的毒性。我们的研究表明，化合物 8 f 有望成为开发抗胃癌药物的潜在且安全的先导化合物。© 2024 Wiley periodicals LLC。

Given the malignancy of gastric cancer, developing highly effective and low-toxic targeted drugs is essential to prolong patient survival and improve patient outcomes. In this study, we conducted structural optimizations based on the benzimidazole scaffold. Notably, compound 8 f presented the most potent antiproliferative activity in MGC803 cells and induced cell cycle arrest at the G0/G1 phase. Further mechanistic studies demonstrated that compound 8 f caused the apoptosis of MGC803 cells by elevating intracellular reactive oxygen species (ROS) levels and activating the mitogen-activated protein kinase (MAPK) signaling pathway, accompanied by corresponding markers change. In vivo investigations additionally validated the inhibitory effect of compound 8 f on tumor growth in xenograft models bearing MGC803 cells without obvious toxicity. Our studies suggest that compound 8 f holds promise as a potential and safe lead compound for developing anti-gastric cancer agents.© 2024 Wiley Periodicals LLC.