Antibacterial and Inhibitory Activity of Nora and Mepa Efflux Pumps of Estragole Complexed to β-Cyclodextrin (ES/β-CD) In Vitro Against Staphylococcus aureus Bacteria, Molecular Docking and MPO-Based Pharmacokinetics Prediction.

Autor: Costa RHSD; Veterinary Medicine Course, Maurício de Nassau University Center, Juazeiro do Norte 63010-475, CE, Brazil.; Laboratory of Pharmacology and Molecular Chemistry (LFQM), Department of Biological Chemistry, Regional University of Cariri, Rua Coronel Antônio Luis 1161, Pimenta, Crato 63105-000, CE, Brazil., Pessoa RT; Laboratory of Pharmacology and Molecular Chemistry (LFQM), Department of Biological Chemistry, Regional University of Cariri, Rua Coronel Antônio Luis 1161, Pimenta, Crato 63105-000, CE, Brazil., Silva EDS; Laboratory of Pharmacology and Molecular Chemistry (LFQM), Department of Biological Chemistry, Regional University of Cariri, Rua Coronel Antônio Luis 1161, Pimenta, Crato 63105-000, CE, Brazil., Araujo IM; Laboratory of Microbiology and Molecular Biology, Department of Biological Chemistry, Regional University of Cariri, Rua Coronel Antônio Luis 1161, Crato 63105-000, CE, Brazil., Gonçalves SA; Laboratory of Microbiology and Molecular Biology, Department of Biological Chemistry, Regional University of Cariri, Rua Coronel Antônio Luis 1161, Crato 63105-000, CE, Brazil., Rocha JE; Laboratory of Microbiology and Molecular Biology, Department of Biological Chemistry, Regional University of Cariri, Rua Coronel Antônio Luis 1161, Crato 63105-000, CE, Brazil., Pereira Junior FN; Center for Agricultural and Biodiversity Sciences, Federal University of Cariri, Crato 63130-025, CE, Brazil., Oliveira NC; Department of Physics, Regional University of Cariri, Juazeiro do Norte 63041-145, CE, Brazil., Oliveira VM; Program in Natural Sciences, State University of Ceará, Fortaleza 60714-903, CE, Brazil., Rocha MND; Program in Natural Sciences, State University of Ceará, Fortaleza 60714-903, CE, Brazil., Marinho ES; Program in Natural Sciences, State University of Ceará, Fortaleza 60714-903, CE, Brazil., Kelly Gomes de Carvalho N; Laboratory of Research and Natural Product (LPPN), Department of Biological Chemistry, Regional University of Cariri, Rua Coronel Antônio Luis 1161, Pimenta, Crato 63105-000, CE, Brazil., Galberto Martins da Costa J; Laboratory of Research and Natural Product (LPPN), Department of Biological Chemistry, Regional University of Cariri, Rua Coronel Antônio Luis 1161, Pimenta, Crato 63105-000, CE, Brazil., Santos HSD; Center for Exact Sciences and Technology, Vale do Acaraú University, Sobral 62040-370, CE, Brazil., Menezes IRA; Laboratory of Pharmacology and Molecular Chemistry (LFQM), Department of Biological Chemistry, Regional University of Cariri, Rua Coronel Antônio Luis 1161, Pimenta, Crato 63105-000, CE, Brazil.
Jazyk: angličtina
Zdroj: Pharmaceutics [Pharmaceutics] 2024 Nov 18; Vol. 16 (11). Date of Electronic Publication: 2024 Nov 18.
DOI: 10.3390/pharmaceutics16111469
Abstrakt: Background/Objectives: The work investigates the effect of the estragole complex encapsulated in beta-cyclodextrin (ES/β-CD) in modulating bacterial resistance, specifically in Staphylococcus aureus strains expressing NorA and MepA efflux pumps. Efflux pumps are mechanisms that bacteria use to resist antibiotics by expelling them from the cell. Methodology: Several compounds and antibiotics, such as ciprofloxacin and norfloxacin, were used to evaluate the antimicrobial activity and the ability of the ES/β-CD complex to reverse resistance. Methods: The study included scanning electron microscopy assays, minimum inhibitory concentration (MIC) determination, and efflux pump inhibition tests. Results: The ES/β-CD complex did not show significant direct antibacterial activity. However, it modulated the action of norfloxacin, decreasing the MIC when combined with this antibiotic in the 1199B (NorA) strain. These results suggest a potential for synergy but not a direct inhibition of efflux pumps. Conclusion: ES/β-CD can potentiate the efficacy of some antibiotics but does not directly act as an efflux pump inhibitor; it is more of an antibiotic potentiator than a direct solution to bacterial resistance. The molecular docking simulation data suggest its high affinity for forming the ES/β-CD complex. The pharmacokinetic predictions based on MPO suggest that the compound has moderate lipophilicity, highly effective cellular permeability, and low incidence of organic toxicity, pointing to a promising pharmacological principle with controlled daily oral dosing. Conclusions: These results indicate this complex's possible and relevant association as an adjuvant in antibiotic therapy to reduce multidrug-resistant bacteria; however, new in vivo assays are necessary to confirm this effect.
Databáze: MEDLINE
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