SYNTHESIS, ANTIMICROBIAL, AND ANTITUBERCULAR ACTIVITIES OF NOVEL N-PYRAZOLYLBENZAMIDE DERIVATIVES

Abstract

The current study investigated the antimicrobial and antitubercular activities of novel N-Pyrazolyl Benzamide derivatives. The study includes the synthesis, characterization, and ligand-based molecular docking of the designed molecules. Synthesis of N-Pyrazolyl Benzamide derivatives involves a two-step process in which 5-amino pyrazole (3) intermediate is produced by the condensation reaction of aryl hydrazine (1) and β-keto nitrile (2) in acidic conditions. The final N-Pyrazolyl Benzamide derivatives (5a-n) were synthesized by the reaction involving amide coupling between 5-amino pyrazole (3) and various substituted benzoyl halides (4a-n). The compounds (5a-n) were tested for antimicrobial activity against two gram-negative strains (E. coli and S. Typhi), two gram-positive strains (S. aureus and B. subtilis) and M. tuberculosis MTB H37Rv (ATCC 27294) strains were used for evaluating antitubercular activity. Molecular docking studies of designed derivatives were performed with the Schrodinger glide package against mycobacterial pantothenate synthetase (PDB ID: 4MQ6). All the tested compounds displayed moderate to good antimicrobial and antitubercular activity against the selected strains of bacteria. All the docked molecules were found occupying the active site and established a minimum of two hydrogen bond interactions in molecular docking studies