Copper(II) aromatic heterocyclic complexes of Gatifloxacin with multi-targeting capabilities for antibacterial therapy and combating antibiotic resistance.

Abstract

In recent years, the pace of novel antibiotic development has been relatively slow, intensifying the urgency of the antibiotic resistance issue. Consequently, scientists have turned their attention to enhancing antibiotic activity by coordinating antibiotics with metal elements. This study designs and synthesizes three novel antibacterial copper complexes based on Gatifloxacin. These complexes exhibit potent antibacterial activity, notably Cu-1, with a minimum inhibitory concentration (MIC) of only 0.063 μg/mL against Staphylococcus aureus (S.aureus), demonstrating potent bacteriostatic capabilities. Further investigations unveil the antibacterial mechanisms of complex Cu-1, revealing its ability not only to suppress the activities of DNA gyrase and topoisomerases IV, but also to effectively inhibit biofilm formation and disrupt the integrity of cell membrane. This multi-targeting action contributes to mitigating the risk of bacterial resistance emergence. Additionally, synergy between Cu-1 and conventional antibiotics is confirmed through checkerboard assays, offering novel strategies for antibacterial therapy. In vivo experiments using a murine model of S.aureus infection demonstrate the significant antibacterial efficacy of Cu-1, providing robust support for its potential in treating S.aureus infections. This study demonstrates that the coordination complexes formed by copper, Gatifloxacin and suitable aromatic heterocyclic ligands exhibit multi-targeting characteristics against bacteria, offering a new direction for combating antibiotic resistance in antibacterial therapy.