Pyrazole Amides Towards Trailblazing Antimicrobial Research: Bridging in Vivo Insights and Molecular Docking Studies

Antimicrobial resistance presents a significant threat to contemporary healthcare systems, making it increasingly difficult to treat infections that were once easily managed. This study aims to assess the efficacy of pyrazole benzamide derivatives (M5a–M5o), which were synthesized for their antimicrobial and antifungal activities. These compounds were tested against methicillin resistant staphylococcus aureus (MRSA), vancomycin resistant staphylococcus aureus (VRSA), mycobacterium tuberculosis H37Rv and other resistant species. The minimum inhibitory concentrations (MIC) were determined using standardized protocols to evaluate their potency and effectiveness. Molecular docking studies were also conducted to explore potential interactions and binding affinities at the molecular level, providing further insights into their antimicrobial and anti-tubercular mechanisms. Compounds M5i, M5k, and M5b emerged as the most potent, displaying MIC value of 3.12 μg/ml. These compounds show great potential as new agents in addressing the growing problem of antimicrobial resistance. Molecular docking studies against Enoyl-[acyl-carrier-protein] reductase (4DRE), revealed key interactions, with compound M5n showing a docking energy of -9.8 kcal/mol and compound M5g at -9.6 kcal/mol. These compounds formed important hydrogen bonds and π-interactions with residues like Lys165, Gly14, Ser94, and Ile21. Overall, the findings indicate that specific pyrazole-benzamide derivatives exhibit promising antimicrobial and antifungal activities, underscoring their potential as therapeutic agents. Additionally, the integration of molecular docking studies proves valuable in guiding the development and optimization of these compounds for future therapeutic applications.