An Investigation into Antibacterial Activity of Fluoroquinolone-Derived Compounds on Two Gram-Negative Bacteria; Escherichia coli and Pseudomonas aeruginosa
Dr. Gholamhossein Hassanshahi,
Molecular Medicine Research Center, Research Institute of Basic Medical Sciences, School of Medicine, Rafsanjan University of Medical Sciences, Pistachio Blvd., Rafsanjan, Kerman, Iran.
Introduction: Quinolones are known as a class of antibiotics inhibiting two central enzymes involved in DNA replication and transcription i.e., DNA gyrase and topoisomerase IV. Among them, fluoroquinolones can be developed via substituting fluorine atoms at the sixth position of core quinolone structure, thereby enhancing antibacterial activity. As a result, growth and proliferation of bacteria may be prevented through new compounds derived from fluoroquinolones and somehow may strengthen their antibacterial effects.
Aim: To assess the probable antibacterial activity of two fluoroquinolone derivatives on Pseudomonas aeruginosa and Escherichia coli as two gram-negative resistant bacteria.
Materials and Methods: The present study was designed and conducted to measure inhibitory concentrations of N-4-methyl (phenyl)-2,2,2-trifluoroacetimidoyl ciprofloxacin (5a) and N-4-methyl (phenyl)-2,2,2-trifluoroacetimidoyl norfloxacin (5b) as two synthetic derivatives of fluoroquinolones. In addition, real-time PCR (RT-PCR) technique was used to assay the performance of these two derivatives on DNA gyrase gene expression levels in Escherichia coli (E. coli) and Pseudomonas aeruginosa (P. aeruginosa) as gram-negative bacteria. Broth microdilution method and disc diffusion test were also employed to determine the Minimum Inhibitory Concentration (MIC) of these synthetic compounds in comparison with conventional antibiotics of gentamycin and ciprofloxacin (a fluoroquinolone). The p<0.05 was assumed as statistically significant.
Results: According to the findings; Zone Of Inhibition (ZOI) of 5a in P. aeruginosa and E. coli (18.5±0.1 and 13.2±0.1 mm respectively) compared with ZOI of ciprofloxacin (28.0±2.0 mm and 18.3.±0.1 mm) and gentamycin (21±0.1 mm and 19.0±0.1 mm). There was no significant difference between the antibacterial effect of 5a and tested antibiotics (p>0.05). So, their antibacterial effects were assumed to be less than the given antibiotics. In contrast, 5b generated a diameter of ZOI in P. aeruginosa and E. coli (28±0.1 and 38±0.1 mm) in comparison with ciprofloxacin (28.0±0.1 and 17.9±0.1 mm) and gentamycin (21±0.1 mm and 19.0±0.1 mm) showed a statistically significant difference (p<0.001). The results of the broth microdilution method also confirmed findings from the disc diffusion test. On the other hand, 5b brought about a significant reduction of DNA gyrase expression levels in both bacteria, while 5a did not show such a significant effect in this domain.
Conclusion: The results of this study suggested that 5b could be used as a new and alternative antibiotic for gentamycin or ciprofloxacin against infections caused by E. coli and P. aeruginosa. However, further research focused on various dimensions, including corresponding complications, as well as clinical trials are required to draw a definite conclusion on these synthetic compounds.