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There is a significant need for new antibacterial agents as pathogenic bacteria continue to threaten human health through the acquisition of resistance and tolerance towards existing antibiotics. Over the last several years, our group has been developing a novel series of halogenated phenazines that demonstrate potent antibacterial and biofilm eradication activities against critical Gram-positive pathogens, including: Staphylococcus aureus, Staphylococcus epidermidis and Enterococcus faecium. Here, we report the design, chemical synthesis and initial biological assessment of a halogenated phenazine–erythromycin conjugate prodrug 5 aimed at enhancing the translational potential for halogenated phenazines as a treatment of bacterial infections.

Graphical abstract: Design, synthesis and biological evaluation of a halogenated phenazine-erythromycin conjugate prodrug for antibacterial applications

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