A novel sulfonamide derivative suppresses gastrointestinal cancer progression by targeting Axin2 and β-catenin

Gastrointestinal cancer is a major global health risk with rising incidence and limited effective therapeutic options. Despite advancements in diagnostics and therapies, the aggressive nature of these malignancies make novel therapeutic strategies essential. This study synthesized and evaluated a novel sulfonamide derivative, compound 2406, for its antiproliferative effects in gastrointestinal cancer cell lines (EC-9706, SGC-7901, and HT-29). Molecular docking and biological assays were conducted to assess its potential binding and interaction with β-tubulin and the Wnt/β-catenin signaling pathway, with a focus on EC-9706 and HT-29 cell lines. Compound 2406 significantly inhibited tumor cell invasion, migration, and colony formation. It induced G2/M phase cell cycle arrest in EC-9706 and HT-29 cells, reducing cellular proliferation. Molecular docking and in vitro experiments confirmed that compound 2406 interfered with β-tubulin cytoskeletal integrity and suppressed Wnt/β-catenin signaling, which is critical for tumor progression. These findings highlight the therapeutic potential of compound 2406 as a novel anticancer agent targeting β-tubulin and Wnt/β-catenin signaling in gastrointestinal cancer. Further in vivo studies would be warranted to validate its efficacy and clinical applicability.