Abstract
Isoxazole-triazole conjugates (8a-q) were synthesized using click chemistry approach and their biological activities were explored to develop novel antibacterial agents. In vitro antibacterial screening against Gram-positive as well as Gram-negative bacterial strains identified compounds 8b and 8m with potent inhibitory potential against selective bacterial cells. 8b showed IC50 value of 67.6 μg/mL against P. aeruginosa while 8m exhibited better activity against Gram-positive bacteria S. pneumoniae and E. faecalis having IC50 values 74.13 and 44.7 μg/mL, respectively. Effect on growth kinetics of the bacterial cells as well as cytotoxicity studies on human embryonic kidney cells (HEK293) further supports their biological potential. Compound 8m significantly inhibited biofilm formation of E. coli cells visualized by scanning electron microscopy (SEM) analysis. The interaction of these compounds with ctDNA, as their possible mode of action, was studied using multi-spectroscopic techniques and molecular docking. The data suggested that compound 8m intercalate in the minor groove of DNA.
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•Novel isoxazole-1,2,3-triazole conjugates (8a-q) were synthesized and confirmed by multi spectroscopic analysis.•In vitro antibacterial screening against various bacterial strains showed compound 8m as potential lead inhibitor.•Cytotoxicity assay on HEK293 cells showed non-toxic nature of the lead compound.•XTT assay and SEM analysis confirmed that compound 8m significantly inhibited biofilm formation.•DNA binding studies of 8m showed intercalating mode of binding.