Design, synthesis, and antimicrobial evaluation of new antipyrine derivatives bearing thiazolopyridazine and pyrazolothiazole scaffolds

In the current research, a new set of antipyrine-thiazole hybrids were designed and synthesized and screened for their antimicrobial activities against Gram-positive and Gram-negative bacteria and fungal strains using ciprofloxacin and nystatin as reference drugs. The antipyrine derivatives 3a, 5a, 7c, and 11a revealed promising and broad antibacterial activity especially against S. aureus, followed by in vitro enzyme inhibitory assay against S. aureus DNA gyrase to predict the mechanism of action. The thiazole 3a and pyrazolo[4,3d]thiazole 7c afforded superior inhibitory activity against S. aureus DNA gyrase (IC50 = 0.292 +/- 0.15 and 0.255 +/- 0.10 mM, respectively) in comparison with ciprofloxacin (IC50 = 0.331 +/- 0.20 mM). Finally, the in silico molecular docking and ADME studies were established to give better rationalization and optimization of efficient new antimicrobial leads. [GRAPHICS]