Impact Factor 2020 : 1.545 (@Clarivate Analytics)
  • Users Online: 228
  • Print this page
  • Email this page
ORIGINAL ARTICLE
Year : 2021  |  Volume : 11  |  Issue : 9  |  Page : 405-413

Antibacterial activity and inhibition against Staphylococcus aureus NorA efflux pump by ferulic acid and its esterified derivatives


1 Departamento de Química Biológica, Programa de Pos-Graduação em Química Biológica, Universidade Regional do Cariri – URCA, Crato – CE, Brazil
2 Programa de Pós-Graduação em Química, Centro de Ciências, Universidade Federal do Ceará – UFC, Fortaleza – CE, Brazil

Correspondence Address:
Henrique Douglas Melo Coutinho
Departamento de Química Biológica, Programa de Pos-Graduação em Química Biológica, Universidade Regional do Cariri – URCA, Crato – CE
Brazil
Irwin Rose Alencar de Menezes
Departamento de Química Biológica, Programa de Pos-Graduação em Química Biológica, Universidade Regional do Cariri – URCA, Crato – CE
Brazil
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2221-1691.321130

Get Permissions

Objective: To evaluate the inhibitory activity of ferulic acid and four of its esterified derivatives (methyl, ethyl, propyl, and butyl) against resistance mechanisms in Staphylococcus aureus strains. Methods: Ferulic acid derivatives were obtained by esterification with methanol, ethanol, propanol, and butanol, and then characterized by hydrogen and carbon-13 nuclear magnetic resonance analysis. The minimum inhibitory concentrations (MIC) of ferulic acid and its esterified derivatives, ethidium bromide, and norfloxacin were obtained using the microdilution test, while the efflux pump inhibition test was conducted by examining reduction in the MICs of norfloxacin and ethidium bromide. Molecular docking was also carried out using the Schrodinger Suite 2015 molecular modeling software. A three-dimensional model of NorA efflux pump was generated using I-TASSER. The best scoring model was used as a receptor for ligand-receptor docking. Results: The methyl and butyl ester derivatives did not demonstrate significant antimicrobial activity. However, a significant synergic effect was evidenced when norfloxacin was combined with the ethyl and propyl esterified derivatives. The docking study demonstrated favorable energy of interaction between ferulate derivatives and NorA, and amino acid residues TYR57, TYR58, and LEU255 were present commonly in stabilizing all complexes. The PCA analysis corroborated the docking hypothesis that the lipophilic character and hydrogen bond interactions were the most relevant characteristics involved with NorA inhibitors. The pharmacokinetic parameters of ferulic acid derivatives showed good ADMET properties, demonstrating that they can be easily absorbed and have no effect or inhibit the cytochrome P450 enzyme complex, revealing their potential as drug candidates. Conclusions: This study provides strong evidence that the molecular basis for this activity is potentially due to the NorA efflux pump.


[FULL TEXT] [PDF]*
Print this article     Email this article
 Next article
 Previous article
 Table of Contents

 Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
 Citation Manager
 Access Statistics
 Reader Comments
 Email Alert *
 Add to My List *
 * Requires registration (Free)
 

 Article Access Statistics
    Viewed414    
    Printed0    
    Emailed0    
    PDF Downloaded55    
    Comments [Add]    

Recommend this journal