{Reference Type}: Journal Article
{Title}: Benzimidazole-based structure optimization to discover novel anti-gastric cancer agents targeting ROS/MAPK pathway.
{Author}: Jia G;Wang Y;Wang J;Yu B;Zhao H;Zhao Z;Zhao W;Gao Y;Wang B;Song Z;
{Journal}: J Biochem Mol Toxicol
{Volume}: 38
{Issue}: 7
{Year}: 2024 Jul
{Factor}: 3.568
{DOI}: 10.1002/jbt.23762
{Abstract}: 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.