Investigation of the Effects of Benzimidazole Derivatives on the mTOR Pathway in Breast Cancer

The mammalian target of rapamycin (mTOR) pathway plays a critical role in cancer progression, making it a key target for therapeutic intervention. Dysregulation of mTOR signaling is frequently observed in malignancies, highlighting the need for potent and selective inhibitors. In this study, a series of benzimidazole derivatives were designed and evaluated for their potential as mTOR inhibitors. Cytotoxicity assessments using MTT assays demonstrated that compounds 10 and 15 exhibited significant anti-proliferative effects against breast cancer cell lines, with IC₅₀ values of 6.63 µM and 5.28 µM, respectively. Further biochemical studies revealed that the most active compounds effectively suppressed mTOR phosphorylation at Ser2448 in MCF-7 cells, as confirmed by colorimetric enzymatic activity assays. These results suggest that compound 15, in particular, represents a promising lead for the development of novel mTOR-targeted therapies. This study provides valuable insights into the structure-based design of mTOR inhibitors, offering a foundation for future advancements in targeted cancer treatment.