1,2,3-Triazole-tethered fluoroquinolone analogues with antibacterial potential: synthesis and in vitro cytotoxicity investigations†

Abstract

The antibacterial efficacy of some newly developed bis- and C3-carboxylic moieties of fluoroquinolone-linked triazole conjugates was studied. Twenty compounds from two different series of triazoles were synthesized using click chemistry and evaluated for their antibacterial activity against a Gram-positive strain, i.e. Enterococcus faecalis (ATCC29212), and its clinical isolate and a Gram-negative bacterial strain, i.e. Escherichia coli (ATCC25922), and its clinical isolate. Among the compounds, 7, 9a, 9d, 9i, 10(a–d), and 10i showed excellent activity with MIC values of up to 6.25 μg mL⁻¹, whereas the control ciprofloxacin showed MIC values of up to 12.5 μg mL⁻¹ towards the various strains. Cytotoxicity was evaluated against Vero cells (kidney epithelial cells of an African green monkey), and results revealed that compounds 9a, 9c, 10g, 10h, and 10 are toxic. Molecular docking and MD analysis were performed using the protein structure of E. coli DNA gyrase B and further corroborated with an in vitro assay to evaluate the inhibition of DNA gyrase. The analysis revealed that compound 10d was a more potent inhibitor of DNA gyrase compared to ciprofloxacin, which was employed as the positive control.