Screening and Evaluation of Potential Efflux Pump Inhibitors with a Seaweed Compound Diphenylmethane-Scaffold against Drug-Resistant Escherichia coli

Drug-resistant efflux pumps play a crucial role in bacterial antibiotic resistance. In this study, potential efflux pump inhibitors (EPIs) with a diphenylmethane scaffold were screened and evaluated against drug-resistant . Twenty-four compounds were docked against the drug-binding site of multidrug...

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Bibliographic Details
Published in:Antibiotics (Basel) 2024-07, Vol.13 (7), p.628
Main Authors: Lu, Wen-Jung, Lian, Yu-Wei, Chang, Chun-Ju, Lin, Hsuan-Ju, Huang, Chian-Yun, Hsu, Pang-Hung, Lin, Hong-Ting
Format: Article
Language:English
Subjects:
Acetonitrile
Algae
Antibiotic resistance
Antibiotics
Bacteria
Binding sites
Cytotoxicity
Damage accumulation
Diphenyl methane
Drug dosages
drug efflux
Drug resistance
Drug resistance in microorganisms
drug transporters
E coli
Efflux
efflux pump inhibitors
Erythromycin
Escherichia coli
Ethidium bromide
Free energy
Gram-negative bacteria
Inhibitors
Membrane permeability
Modulation
molecular docking
multidrug resistance
Penicillin G
Pharmaceutical industry
Scaffolds
Seaweeds
Tetracycline
Tetracyclines
Toxicity
Toxicity testing
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Summary:Drug-resistant efflux pumps play a crucial role in bacterial antibiotic resistance. In this study, potential efflux pump inhibitors (EPIs) with a diphenylmethane scaffold were screened and evaluated against drug-resistant . Twenty-four compounds were docked against the drug-binding site of multidrug transporter AcrB, and 2,2-diphenylethanol (DPE), di- -tolyl-methanol (DPT), and 4-(benzylphenyl) acetonitrile (BPA) were screened for their highest binding free energy. The modulation assay was further used for EPI evaluation, revealing that DPE, DPT, and BPA could reduce the drug IC value in strains overexpressing AcrB, indicating their modulation activity. Only DPE and BPA enhanced intracellular dye accumulation and inhibited the efflux of ethidium bromide and erythromycin. In addition, DPE and BPA showed an elevated post-antibiotic effect on drug-resistant , and they did not damage the permeability of the bacterial outer membrane. The cell toxicity test showed that DPE and BPA had limited human-cell toxicity. Therefore, DPE and BPA demonstrate efflux pump inhibitory activity, and they should be further explored as potential enhancers to improve the effectiveness of existing antibiotics against drug-resistant .
ISSN:2079-6382
2079-6382
DOI:10.3390/antibiotics13070628