Assessment of the antimicrobial properties of novel azopyrazolo[1,5-a]pyrimidine derivatives targeting DNA gyrase enzyme: design, synthesis, and molecular docking studies.

Novel azopyrazolo[1,5-a]Pyrimidines were produced and assessed for their in vitro antibacterial efficacy. The results demonstrated significant antibacterial efficacy against two gram-positive and two gram-negative bacterial species, besides one fungal strain. 5d and 5i-k displayed significant antibacterial efficacy against all the evaluated bacterial strains having a range of MIC = 7.8-500 μg/mL comparing to Cefotaxime and Ciprofloxacin as commercial drugs. Furthermore, 5d, i, and k exhibited elevated IC50 values on normal cells (80.12, 66.34, 92.1 μM), respectively, suggesting their possible selectivity. Furthermore, they exhibited significant inhibitory effects on the DNA gyrase enzyme. The pyrazolo[1,5-a]pyrimidines (5d, i, and k) exhibited significant inhibitory activity on DNA gyrase, with IC50 values ranging from 1.76 to 3.04 μM, equivalent to Ciprofloxacin. A decrease in the quantity of viable cells was observed, which was both concentration-dependent and time-dependent in the time-kill kinetics profile of the most effective compounds against St. aureas, E. coli, B. subtilis, Pseud. aeruginosa, and Candida albicans, especially, compound 5k presented the most bactericidal activity against the tested bacterial strains. Moreover, a docking investigation of the most potent derivatives was conducted within the binding site of DNA gyrase, demonstrating concordance with the in vitro inhibitory effects.