Natural Berberine-derived Azolyl Ethanols as New Structural Antibacterial Agents against Drug-Resistant Escherichia coli

Natural berberine-derived azolyl
ethanols as new structural antibacterial
agents were designed and synthesized for fighting with dreadful bacterial
resistance. Partial target molecules exhibited potent activity against
the tested strains, particularly, nitroimidazole derivative 4d and benzothiazole-2-thoil compound 18b, with
low cytotoxicity both exerted strong antibacterial activities against
multidrug-resistant Escherichia coli at low concentrations as 0.007 and 0.006 mM, respectively. Meanwhile,
the active compounds 4d and 18b possessed
the ability to rapidly kill bacteria and observably eradicate the E. coli biofilm by reducing exopolysaccharide content
to prevent bacterial adhesion, which was conducive to alleviating
the development of E. coli resistance.
Preliminary mechanistic explorations suggested that the excellent
antibacterial potential of molecules 4d and 18b might be attributed to their ability to disintegrate membrane, accelerate
ROS accumulation, reduce bacterial metabolism, and intercalate into
DNA groove. These results provided powerful information for the further
exploitation of natural berberine derivatives against bacterial pathogens.