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

Abstract

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[4,3-d]thiazole 7c afforded superior inhibitory activity against S. aureus DNA gyrase (IC₅₀ = 0.292 ± 0.15 and 0.255 ± 0.10 µM, respectively) in comparison with ciprofloxacin (IC₅₀ = 0.331 ± 0.20 µM). Finally, the in silico molecular docking and ADME studies were established to give better rationalization and optimization of efficient new antimicrobial leads.

Graphical Abstract

Keywords:

• antipyrine
• thiazole
• antimicrobial
• S. aureus DNA gyrase
• in silico studies

Acknowledgments

The research work was funded by the Deanship of Scientific Research (DSR), King Abdulaziz University, Jeddah, Saudia Arabia, under grant No. (J-615-130-1436). The author, therefore, acknowledges with thanks DSR technical and financial support.

Disclosure statement

No potential conflict of interest was reported by the author.