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

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-isobut...

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Published in:	Microbial pathogenesis Vol. 170; p. 105697
Main Authors:	Xavier, Maria R., Freitas, Thiago S., Pereira, Raimundo L.S., Marinho, Emanuelle M., Bandeira, Paulo N., de Sousa, Amanda P., Oliveira, Larissa S., Bezerra, Lucas Lima, Neto, José B.A., Silva, Maria M.C., Cruz, Beatriz G., Rocha, Janaína E., Barbosa, Cristina R.S., da Silva, Antonio W., de Menezes, Jane E.S.A., Coutinho, Henrique D.M., Marinho, Márcia M., Marinho, Emmanuel S., dos Santos, Hélcio S., Teixeira, Alexandre M.R.
Format:	Journal Article
Language:	English
Published:	Elsevier Ltd 01-09-2022
Subjects:	Anti-inflammatory activity Antibacterial activity Efflux pump Ibuprofen derivative Multidrug-resistant bacteria Anti-inflammatory activity Antibacterial activity Ibuprofen derivative Efflux pump Multidrug-resistant bacteria
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Summary:	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. [Display omitted] •Anti-inflammatory and antibacterial evaluation of an ibuprofen derivative.•Antibiotic inhibition mechanisms were evaluated.•Antibiotic potentiation occurs when MET-IBU is associated with antibiotics.•MET-IBU presents anti-inflammatory activity in adult zebrafish model.•MET-IBU possesses inhibitory effect on the MepA efflux pump.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0882-4010 1096-1208
DOI:	10.1016/j.micpath.2022.105697