Evaluation of the Activity of Amino Chalcone Against Staphylococcus Strains Harboring Efflux Pumps

The emergence of efflux-mediated resistance in Staphylococcus aureus has limited the effectiveness of conventional antibiotics, highlighting the need for novel adjuvant compounds. This study investigated the synthetic chalcone CMA4DMA as a potential modulator of bacterial resistance associated with the NorA efflux pump. In vitro anti-microbial assays showed that CMA4DMA displayed no intrinsic antibacterial effect (MIC ≥ 1024 µg/mL) but significantly reduced the minimum inhibitory concentration of norfloxacin and ethidium bromide in both wild-type SA1199 and NorA-overexpressing SA1199B strains. Fluorescence assays demonstrated increased intracellular accumulation of ethidium bromide without affecting membrane permea-bility, supporting an efflux-inhibitory mechanism. Molecular docking analysis revealed that CMA4DMA binds to the same site as norfloxacin in the NorA protein, engaging in hydrophobic and hydrogen-bond interactions with key residues, consistent with direct inhibition. In silico ADMET predictions indicated favorable oral absorption and distri-bution, though possible rapid metabolism and risks of hepatotoxicity and cardiotoxici-ty warrant caution for further development. Overall, CMA4DMA effectively restored antibiotic susceptibility in resistant S. aureus strains and showed a consistent inhibitory effect when compared with studies involving other efflux systems, reinforcing its po-tential as a promising scaffold for the development of new bacterial resistance modu-lators.