Synthesis, characterization in vitro antimicrobial evaluation and in silico approach of molecular docking of pyrazole based pyrimidine and pyrazolone motifs

In the past few decades, mankind is suffering from tormented life-threatening infectious diseases caused by multidrug-resistant bacteria. As a result, new antimicrobial classes with distinct modes of action are required to combat multidrug-resistant infections. The pyrazole-based pyrimidine and pyrazolone motifs were synthesized, characterized, and screened for their antimicrobial activity. Molecular docking was carried out for the development of antimicrobial agents based on the results of biological activity obtained. : We have synthesized a new series of pyrazole containing pyrimidine-pyrazolone hybrids by using multi-step reactions in the search of antimicrobial agents (7a-o). The structures were determined by 1H NMR, 13C NMR, IR, and mass spectroscopy techniques. Moreover, synthesized compounds were evaluated for their antimicrobial activity by using serial Broth dilution method. Antimicrobial activity of synthesized compounds has been tested against bacterial and fungal strains. Compound 7o was most effective against S. aureus with MIC = 0.096 M/mL. A molecular docking study against microbial DNA gyrase revealed important information about the mechanisms underlying antimicrobial efficacy. Through significant interactions with active site residues, all of the compounds were able to dock well into the enzyme's active site. Furthermore, Compounds 7a (0.531 M/mL), 7b (0.456 M/mL), and 7m (0.485 M/mL) showed excellent antifungal activity against C. albicans compared to the positive control griseofulvin. It has been concluded that compounds containing electron-donating groups are found to be most active against bacterial strains while compounds having both electron-donating as well as electron-withdrawing groups are most favorable for antifungal activity.