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Indole derivatives 3-amino-6-carboxyl-indole and 3-nitro-6-amino-indole were designed and synthesized based on the TolC structure. They proved to have potent synergistic antibacterial effects on chloramphenicol, tetracycline, erythromycin, and ciprofloxacin against Escherichia coli YD2 and FJ307 with decreased minimal inhibitory concentrations (MICs) at 2-64 folds. To research its functional site, Escherichia coli BL21(DE3)-3 expressing a target-site mutated TolC was constructed by red homologous recombination and the site-directed mutagenesis technique. They did not noticeably affect antimicrobial activity against BL21(DE3)-3. All the results indicate that these compounds match our design and can be developed as efflux pump inhibitors for the AcrAB-TolC efflux pump.

Evaluation and Target Validation of Indole Derivatives as Inhibitors of the AcrAB-TolC Efflux Pump