Synthesis, Antiproliferative Activity Evaluation, and Computational Insights of Benzo[ <i>d</i> ]imidazol‐2(3 <i>H</i> )‐one Derivatives

Abstract In here, three different 1‐(aryl)‐1 H ‐benzo[ d ]imidazol‐2(3 H )‐one derivatives ( 2a–c ) and three different 1,3‐bis(aryl)‐1 H ‐benzo[ d ]imidazol‐2(3 H )‐one ( 3a–c ) were synthesized and characterized. The resulting synthesised compounds ( 2a–c ; 3a–c ) were evaluated in four different cancer cell lines and one healthy human cell line for 48 h. The wet‐lab study demonstrated that compound 3a exhibited higher cytotoxic activity, particularly against the DLD‐1 colon cancer cell line, compared to 2a–c , 3b , and 3c . The mode of action for this activity was explored through molecular docking and molecular dynamics (MD) simulation. The molecular docking study demonstrated that 3a had binding potential to the colon cancer protein. However, the binding potential of 3a was weaker than the standard drug, irinotecan. The MD simulation showed that the protein‐compound complexes procured from the docking were stable enough to remain inside the binding region. Furthermore, the electrochemical properties of the synthesized compounds were investigated through density functional theory (DFT). DFT calculations revealed that the chemical stability of 2a is at the highest level.