Costa Roger Henrique Sousa da, Pessoa Renata Torres, Silva Eduardo Dos Santos, Araujo Isaac Moura, Gonçalves Sheila Alves, Rocha Janaína Esmeraldo, Pereira Junior Francisco Nascimento, Oliveira Naiara Cipriano, Oliveira Victor Moreira de, Rocha Matheus Nunes da, Marinho Emmanuel Silva, Kelly Gomes de Carvalho Natália, Galberto Martins da Costa José, Santos Hélcio Silva Dos, Menezes Irwin Rose Alencar de
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.
Pharmaceutics. 2024 Nov 18;16(11):1469. doi: 10.3390/pharmaceutics16111469.
The work investigates the effect of the estragole complex encapsulated in beta-cyclodextrin (ES/β-CD) in modulating bacterial resistance, specifically in 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. The study included scanning electron microscopy assays, minimum inhibitory concentration (MIC) determination, and efflux pump inhibition tests. 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. 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.
该研究调查了β-环糊精包封的草蒿脑复合物（ES/β-CD）在调节细菌耐药性方面的作用，特别是对表达NorA和MepA外排泵的菌株的影响。外排泵是细菌通过将抗生素排出细胞来抵抗抗生素的机制。方法：使用了几种化合物和抗生素，如环丙沙星和诺氟沙星，来评估抗菌活性以及ES/β-CD复合物逆转耐药性的能力。该研究包括扫描电子显微镜分析、最低抑菌浓度（MIC）测定和外排泵抑制试验。ES/β-CD复合物未显示出显著的直接抗菌活性。然而，它调节了诺氟沙星的作用，在1199B（NorA）菌株中与这种抗生素联合使用时降低了MIC。这些结果表明存在协同作用的潜力，但不是对外排泵的直接抑制。结论：ES/β-CD可以增强某些抗生素的疗效，但不是直接作为外排泵抑制剂；它更像是一种抗生素增效剂，而不是解决细菌耐药性的直接方法。分子对接模拟数据表明其形成ES/β-CD复合物的亲和力很高。基于MPO的药代动力学预测表明，该化合物具有适度的亲脂性、高效的细胞通透性和较低的有机毒性发生率，表明其具有可控的每日口服给药的有前景的药理原理。这些结果表明这种复合物作为抗生素治疗中的佐剂以减少多重耐药细菌可能存在且相关的关联；然而，需要新的体内试验来证实这种效果。
