Design, Synthesis, Antibacterial and Antitubercular Studies of Some New Benzimidazoles. A Combined Experimental and Computational Approach

Abstract A novel series of seventeen 2‐(4‐chlorophenyl)‐1H‐benzo[d]imidazole‐N‐aryl acetamides derivatives 3(a – q) were synthesized by nucleophilic substitution of 2‐chloro‐N‐(aryl)‐acetamides 2(a – q) with 2‐(4‐chlorophenyl)‐1H‐benzo[d]imidazole (1) in N,N‐Dimethylformamide. The literature indicates that the primary compound, 2‐(4‐chlorophenyl)‐1H‐benzo[d]imidazole ( 1 ), not only serves as a synthetic precursor but also exhibit anthelmintic, antiviral, and antifungal activities. The synthesized compounds were estimated for their structures through elemental analysis and spectral data examination. All the compounds be subjected to evaluation for their antibacterial activity against Bacillus subtilis (NCIM 2920), Staphylococcus aureus (NCIM 2901), Escherichia coli (NCIM 2810), Pseudomonas aeruginosa (NCIM 5223), and antimycobacterial activity against Mycobacterium smegmatis (ATCC607). Compound 3 m , exhibit the highest antibacterial activity with a MIC value of 1.562 μg/ml against all tested bacterial strains and compound 3 k , exhibited the highest antimycobacterial activity with a MIC value of 3.96 μg/ml. Additionally, we performed docking investigations of the most active compounds within the active binding site of the co‐crystallized structure of Glucosamine‐6‐phosphate synthase (PDB ID: 2VF5) and Mycobacterium tuberculosis (PDB ID: 2X22).