A New Discovery of Unique 13-(Benzimidazolylmethyl)berberines as Promising Broad-Spectrum Antibacterial Agents

A new hybridization of berberine and benzimidazoles was performed to produce 13-(benzimidazolylmethyl)-berberines (BMB) as potentially broad-spectrum antibacterial agents with the hope of confronting multidrug-resistant bacterial infections in the livestock industry. Some of the newly prepared hybrids showed obvious antibacterial effects against tested strains. Particularly, 13-((1-octyl-benzimidazolyl)methyl)berberine 6f (OBMB-6f) was found to be the most promising compound that not only exerted a strong activity (MIC = 0.25-2 mu g/mL) and low cytotoxicity but also possessed a fast bactericidal capacity and low propensity to develop resistance toward Staphylococcus aureus and Escherichia coli even after 26 serial passages. Moreover, OBMB-6f displayed the ability to prevent bacterial biofilm formation at low and high temperatures. The mechanistic exploration revealed that OBMB-6f could significantly disintegrate bacterial membranes, markedly facilitate intracellular ROS generation, and efficiently intercalate into DNA. These results provided a profound insight into BMB against multidrug-resistant bacterial infections in the livestock industry.

Automated summary

A hybridization of berberine and benzimidazoles produced 13-(benzimidazolylmethyl)-berberines (BMB) as potential broad-spectrum antibacterial agents. Among the synthesized compounds, 13-((1-octyl-benzimidazolyl)methyl)berberine 6f (OBMB-6f) showed the most promising activity with low cytotoxicity, bactericidal capacity, and low propensity for developing resistance. OBMB-6f also demonstrated the ability to prevent bacterial biofilm formation and exhibited mechanisms involving bacterial membrane disruption, intracellular ROS generation, and DNA intercalation.