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Medicinal Chemistry

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ISSN (Print): 1573-4064
ISSN (Online): 1875-6638

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Research Article

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

Author(s): Hina Siddiqui *, Haroon M. Haniffa, Ayaz Ahmed and Muhammad I. Choudhary*

Volume 17, Issue 1, 2021

Published on: 02 April, 2020

Page: [85 - 96] Pages: 12

DOI: 10.2174/1573406416666200402151705

Price: $65

Abstract

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.

Keywords: Enrofloxacin amide derivatives, anti-biofilm, antibacterial activity, Staphylococcus aureus, Klebsiella pneumonia, Gram-negative bacilli.

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