Synthesis of new Enrofloxacin Derivatives as Potential Antibiofilm Drugs Against Staphylococcus Aureus and Klebsiella Pneumoniae.

BACKGROUND

The antimicrobial resistance due to biofilm formation among bacteria is a significant problem in the healthcare and food industries.

OBJECTIVE

The current study describes the synthesis of enrofloxacin derivatives 2-17, and the evaluation of their anti-bacterial and anti-biofilm activities.

METHODS

Compounds 2-17 were synthesized through the acylation of enrofloxacin with thionyl chloride, followed by reaction with different aromatic amines. The new analogues identified among the sixteen compounds were 2-7, 11, 14, and 17.

RESULTS

Compound 2 appeared to be effective against pathogens S. aureus as well as K. pneumonia, whereas, compound 11 was found active against K. pneumonia only. Compound 2 inhibited >75% biofilm formation of S. aureus at 20 μg/mL and K. pneumonia at 10 μg/mL concentrations. These doses are far below the bactericidal concentration of compound 2, suggesting the anti-virulence mechanism of these compounds. Compound 11 inhibited 60% biofilm formation of K. pneumoniae at 70 μg/mL concentration. Compound 5 inhibited the biofilm of K. pneumoniae at 62 μg/mL concentration but also had bactericidal properties at this concentration. Interestingly, compound 2 eradicated the preformed biofilm of both the pathogens at much lower doses as compared to control drug, gentamycin and substrate, enrofloxacin. Cytotoxicity of compounds 2-17 was checked by a standard method using 3T3 normal cell lines (mouse fibroblast), all compounds were found to be noncytotoxic.

CONCLUSION

These compounds can be used alone or with FDA approved drugs to overcome biofilm related K. pneumoniae and S. aureus infections.