Antibacterial and Inhibitory Activity of Nora and Mepa Efflux Pumps of Estragole Complexed to β-Cyclodextrin (ES/β-CD) In Vitro Against <i>Staphylococcus aureus</i> Bacteria, Molecular Docking and MPO-Based Pharmacokinetics Prediction
Roger Henrique Sousa da Costa,
Renata Torres Pessoa,
Eduardo dos Santos Silva,
Isaac Moura Araujo,
Sheila Alves Gonçalves,
Janaína Esmeraldo Rocha,
Francisco Nascimento Pereira Junior,
Naiara Cipriano Oliveira,
Victor Moreira de Oliveira,
Matheus Nunes da Rocha,
Emmanuel Silva Marinho,
Natália Kelly Gomes de Carvalho,
José Galberto Martins da Costa,
Hélcio Silva dos Santos,
Irwin Rose Alencar de Menezes
Affiliations
Roger Henrique Sousa da Costa
Veterinary Medicine Course, Maurício de Nassau University Center, Juazeiro do Norte 63010-475, CE, Brazil
Renata Torres Pessoa
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
Eduardo dos Santos Silva
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
Isaac Moura Araujo
Laboratory of Microbiology and Molecular Biology, Department of Biological Chemistry, Regional University of Cariri, Rua Coronel Antônio Luis 1161, Crato 63105-000, CE, Brazil
Sheila Alves Gonçalves
Laboratory of Microbiology and Molecular Biology, Department of Biological Chemistry, Regional University of Cariri, Rua Coronel Antônio Luis 1161, Crato 63105-000, CE, Brazil
Janaína Esmeraldo Rocha
Laboratory of Microbiology and Molecular Biology, Department of Biological Chemistry, Regional University of Cariri, Rua Coronel Antônio Luis 1161, Crato 63105-000, CE, Brazil
Francisco Nascimento Pereira Junior
Center for Agricultural and Biodiversity Sciences, Federal University of Cariri, Crato 63130-025, CE, Brazil
Naiara Cipriano Oliveira
Department of Physics, Regional University of Cariri, Juazeiro do Norte 63041-145, CE, Brazil
Victor Moreira de Oliveira
Program in Natural Sciences, State University of Ceará, Fortaleza 60714-903, CE, Brazil
Matheus Nunes da Rocha
Program in Natural Sciences, State University of Ceará, Fortaleza 60714-903, CE, Brazil
Emmanuel Silva Marinho
Program in Natural Sciences, State University of Ceará, Fortaleza 60714-903, CE, Brazil
Natália Kelly Gomes de Carvalho
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
José Galberto Martins da Costa
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
Hélcio Silva dos Santos
Center for Exact Sciences and Technology, Vale do Acaraú University, Sobral 62040-370, CE, Brazil
Irwin Rose Alencar de Menezes
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
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.
