Novel terpyridines as Staphylococcus   aureus gyrase inhibitors: efficient synthesis and antibacterial assessment via solvent-drop grinding.

Aim: This study was designed to synthesize a novel series of terpyridines with potential antibacterial properties, targeting multidrug resistance. Materials & methods: Terpyridines ( 4a-h and 6a-c ) were synthesized via a one-pot multicomponent reaction using 2,6-diacetylpyridines, benzaldehyde derivatives and malononitrile or ethyl 2-cyanoacetate. The reactions, conducted under grinding conditions with glacial acetic acid, produced high-yield compounds, confirmed by spectroscopic data. Results: The synthesized terpyridines exhibited potent antibacterial activity. Notably, compounds 4d and 4h demonstrated significant inhibition zones against Staphylococcus aureus and Bacillus subtilis , outperforming ciprofloxacin. Conclusion: Molecular docking studies highlighted compounds 4d , 4h  and 6c as having strong binding affinity to DNA gyrase B, correlating with their robust antibacterial activity, suggesting their potential as effective agents against multidrug-resistant bacterial strains.