Portal de Periódicos da CAPES

Artigo Produção Nacional Revisado por pares

BIBTEX RIS

Anti-inflammatory effect, antibiotic potentiating activity against multidrug-resistant strains of Escherichia coli and Staphylococcus aureus, and evaluation of antibiotic resistance mechanisms by the ibuprofen derivative methyl 2-(-4-isobutylphenyl)propanoate

2022; Elsevier BV; Volume: 170; Linguagem: Inglês

10.1016/j.micpath.2022.105697

1096-1208

Maria R. Xavier, Thiago Sampaio de Freitas, Raimundo Luíz Silva Pereira, Emanuelle Machado Marinho, Paulo Nogueira Bandeira, Amanda Pereira de Sousa, Larissa Santos Oliveira, Lucas Lima Bezerra, José Bezerra de Araújo Neto, Maria Milene Costa da Silva, Beatriz Gonçalves Cruz, Janaína Esmeraldo Rocha, Cristina Rodrigues dos Santos Barbosa, Antonio W. da Silva, Jane Eire Silva Alencar de Menezes, Henrique Douglas Melo Coutinho, Márcia Machado Marinho, Emmanuel Silva Marinho, Hélcio Silva dos Santos, Alexandre Magno Rodrigues Teixeira,

Antibiotic Resistance in Bacteria

The prevalence of multidrug-resistant (MDR) bacteria and the limited efficacy of current available antibiotics cause every year approximately 700 000 deaths per year. This study aimed to evaluate the anti-inflammatory effect and antibacterial potential of the ibuprofen derivative Methyl 2-(-4-isobutylphenyl)propanoate (MET-IBU). The molecular structure of MET-IBU was confirmed by Nuclear Magnetic Resonance (NMR) and, Attenuated Total Reflectance Fourier Transform Infrared spectroscopy (ATR-FTIR) spectroscopy. Our in vivo study using adult zebrafish model demonstrated that the ibuprofen derivative MET-IBU also possesses anti-inflammatory effect, and in vitro antibacterial activity assays showed that in the association of ampicillin, norfloxacin, and gentamicin with MET-IBU occurred reduction in the minimum inhibitory concentration (MIC) for MDR bacterial strains of Escherichia coli 06 and Staphylococcus aureus 10, indicating a potentiating in the growth inhibition of these pathogenic bacteria. Regarding the strain of Staphylococcus aureus K2068 (overexpressing mepA gene), a potentiation of ethidium bromide was found in the association with MET-IBU, indicating the action of this compound on the efflux pump mechanism present in this strains. This result corroborates the molecular docking study that indicated a high affinity of the MET-IBU with the MepA efflux pump. It was also noticed an antibiotic potentiating activity in the association MET-IBU with norfloxacin against strains of Staphylococcus aureus 1199B (overexpressing norA gene) when compared to the norfloxacin control. This enhanced antibiotic effect of MET-IBU is associated with a second resistance mechanism, which is due to the modification in the topoisomerase enzyme. These results bring attention to the ibuprofen derivative MET-IBU as possible candidate for the development of new options for the treatment of bacterial infections with protective anti-inflammatory action.