Design, Synthesis and Anticancer Profile of New 4-(1-benzo[]imidazol-1-yl)pyrimidin-2-amine-Linked Sulfonamide Derivatives with V600EBRAF Inhibitory Effect.

A new series of 4-(1-benzo[]imidazol-1-yl)pyrimidin-2-amine linked sulfonamide derivatives was designed and synthesized according to the structure of well-established V600EBRAF inhibitors. The terminal sulfonamide moiety was linked to the pyrimidine ring via either ethylamine or propylamine bridge. The designed series was tested at fixed concentration (1 µM) against V600EBRAF, finding that , and exhibited the strongest inhibitory activity among all target compounds and had the lowest IC of 0.49 µM. They were further screened on NCI 60 cancer cell lines to reveal that showed the most significant growth inhibition against multiple cancer cell lines. Therefore, cell cycle analysis of was conducted to investigate the effect on cell cycle progression. Finally, virtual docking studies was performed to gain insights for the plausible binding modes of vemurafenib, , and .