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ID: ALA5038640

Journal: J Med Chem

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

Authors: Sun H, Huang SY, Jeyakkumar P, Cai GX, Fang B, Zhou CH.

Abstract: 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.

CiteXplore: 34964345

DOI: 10.1021/acs.jmedchem.1c01592