Generic placeholder image

Medicinal Chemistry

Editor-in-Chief

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

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.

« Previous
Graphical Abstract
[1]
Wright, D.H.; Brown, G.H.; Peterson, M.L.; Rotschafer, J.C. Application of fluoroquinolone pharmacodynamics. J. Antimicrob. Chemother., 2000, 46(5), 669-683.
[http://dx.doi.org/10.1093/jac/46.5.669] [PMID: 11062185]
[2]
Trouchon, T.; Lefebvre, S. A review of enrofloxacin for veterinary use. Open J. Vet. Med., 2016, 6(2), 40-58.
[http://dx.doi.org/10.4236/ojvm.2016.62006]
[3]
Aral, F.; Karaçal, F.; Baba, F. The effect of enrofloxacin on sperm quality in male mice. Res. Vet. Sci., 2008, 84(1), 95-99.
[http://dx.doi.org/10.1016/j.rvsc.2007.04.007] [PMID: 17561208]
[4]
Küng, K.; Riond, J.L.; Wanner, M. Pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin after intravenous and oral administration of enrofloxacin in dogs. J. Vet. Pharmacol. Ther., 1993, 16(4), 462-468.
[http://dx.doi.org/10.1111/j.1365-2885.1993.tb00212.x] [PMID: 8126763]
[5]
Watanabe, H.; Satake, A.; Kido, Y.; Tsuji, A. Monoclonal-based enzyme-linked immunosorbent assay and immunochromatographic rapid assay for salinomycin. Anal. Chim. Acta, 2001, 437(1), 31-38.
[http://dx.doi.org/10.1016/S0003-2670(01)00925-4]
[6]
Hernández, M.; Aguilar, C.; Borrull, F.; Calull, M. 2002.
[7]
Mirzaei, J.; Pirelahi, H.; Amini, M.; Abbas Shafiee, A. Convenient syntheses of 5-[(2-methyl-5-nitro-1H-imidazol-1-yl) methyl] -1, 3, 4-oxadiazole-2 (3H) thione and N-substituted 2-amino-5- [(2-methyl-5-nitro-1H-imidazol-1-yl) methyl] -1, 3, 4-thiadiazoles. J. Heterocycl. Chem., 2008, 45(3), 921-925.
[http://dx.doi.org/10.1002/jhet.5570450343]
[8]
Patel, N.B.; Patel, S.D.; Patel, J.N.; Patel, J.C.; Gorgamwala, Y.S. Synthesis and antibacterial activity of thioureido amide of fluoroquinolone. Int. J. Biol. Chem., 2011, 5(1), 37-45.
[http://dx.doi.org/10.3923/ijbc.2011.37.45]
[9]
Purkayastha, N.; Capone, S.; Beck, A.K.; Seebach, D.; Leeds, J.; Thompson, K.; Moser, H.E. Antibacterial activity of enrofloxacin and ciprofloxacin derivatives of β-octaarginine. Chem. Biodivers., 2015, 12(2), 179-193.
[http://dx.doi.org/10.1002/cbdv.201400456] [PMID: 25676502]
[10]
Choi, J.; Lee, Y.M.; Jee, J.G. Thiopurine drugs repositioned as tyrosinase inhibitors. Int. J. Mol. Sci., 2017, 19(1), 77.
[http://dx.doi.org/10.3390/ijms19010077] [PMID: 29283382]
[11]
Abdel-Monem, W.R. Synthesis and biological evaluations of sulfa derivatives bearing heterocyclic moieties. Boll. Chim. Farm., 2004, 143(6), 239-247.
[PMID: 15881802]
[12]
Ashburn, T.T.; Thor, K.B. Drug repositioning: identifying and developing new uses for existing drugs. Nat. Rev. Drug Discov., 2004, 3(8), 673-683.
[http://dx.doi.org/10.1038/nrd1468] [PMID: 15286734]
[13]
Sisignano, M.; Parnham, M.J.; Geisslinger, G. Drug repurposing for the development of novel analgesics. Trends Pharmacol. Sci., 2016, 37(3), 172-183.
[http://dx.doi.org/10.1016/j.tips.2015.11.006] [PMID: 26706620]
[14]
Miquel, S.; Lagrafeuille, R.; Souweine, B.; Forestier, C. Anti-biofilm activity as a health issue. Front. Microbiol., 2016, 7, 592.
[http://dx.doi.org/10.3389/fmicb.2016.00592] [PMID: 27199924]
[15]
Karatan, E.; Watnick, P. Signals, regulatory networks, and materials that build and break bacterial biofilms. Microbiol. Mol. Biol. Rev., 2009, 73(2), 310-347.
[http://dx.doi.org/10.1128/MMBR.00041-08] [PMID: 19487730]
[16]
Khan, F.; Javaid, A.; Kim, Y-M. Functional diversity of quorum sensing receptors in pathogenic bacteria: Interspecies, intraspecies and interkingdom level. Curr. Drug Targets, 2019, 20(6), 655-667.
[http://dx.doi.org/10.2174/1389450120666181123123333] [PMID: 30468123]
[17]
Roy, R.; Tiwari, M.; Donelli, G.; Tiwari, V. Strategies for combating bacterial biofilms: A focus on anti-biofilm agents and their mechanisms of action. Virulence, 2018, 9(1), 522-554.
[http://dx.doi.org/10.1080/21505594.2017.1313372] [PMID: 28362216]
[18]
Tarr, J.M.; Kaul, K.; Chopra, M.; Kohner, E.M.; Chibber, R. Pathophysiology of diabetic retinopathy. ISRN Ophthalmol., 2013, 2013343560
[http://dx.doi.org/10.1155/2013/343560] [PMID: 24563789]
[19]
Wang, X.; Lünsdorf, H.; Ehrén, I.; Brauner, A.; Römling, U. Characteristics of biofilms from urinary tract catheters and presence of biofilm-related components in Escherichia coli. Curr. Microbiol., 2010, 60(6), 446-453.
[http://dx.doi.org/10.1007/s00284-009-9563-z] [PMID: 20012619]
[20]
Niveditha, S.; Pramodhini, S.; Umadevi, S.; Kumar, S.; Stephen, S. The isolation and the biofilm formation of uropathogens in the patients with catheter associated urinary tract infections (UTIs). J. Clin. Diagn. Res., 2012, 6(9), 1478-1482.
[http://dx.doi.org/10.7860/JCDR/2012/4367.2537] [PMID: 23285434]
[21]
Frieri, M.; Kumar, K.; Boutin, A. Antibiotic resistance. J. Infect. Public Health, 2017, 10(4), 369-378.
[http://dx.doi.org/10.1016/j.jiph.2016.08.007] [PMID: 27616769]
[22]
Navidinia, M. The clinical importance of emerging ESKAPE pathogens in nosocomial infections. J. Paramed. Sci., 2016, 7(3), 43-57.
[23]
Agrawal, A.; Chaudhary, U. Effect of natural compounds on inhibition of biofilm formation of multi drug resistant Staphylococcus aureus and Staphylococcus epidermidis-an in vitro Study. Int. J. Curr. Microbiol. Appl. Sci., 2018, 7(2), 2921-2926.
[http://dx.doi.org/10.20546/ijcmas.2018.702.354]
[24]
Khan, A.K.; Ahmed, A.; Hussain, M.; Khan, I.A.; Ali, S.A.; Farooq, A.D.; Faizi, S. Antibiofilm potential of 16-oxo-cleroda-3, 13(14) E-diene-15 oic acid and its five new γ-amino γ-lactone derivatives against methicillin resistant Staphylococcus aureus and Streptococcus mutans. Eur. J. Med. Chem., 2017, 138, 480-490.
[http://dx.doi.org/10.1016/j.ejmech.2017.06.065] [PMID: 28692914]
[25]
Mosmann, T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J. Immunol. Methods, 1983, 65(1-2), 55-63.
[http://dx.doi.org/10.1016/0022-1759(83)90303-4] [PMID: 6606682]
[26]
Khan, F.; Pham, D.T.N.; Oloketuyi, S.F.; Manivasagan, P.; Oh, J.; Kim, Y-M. Chitosan and their derivatives: Antibiofilm drugs against pathogenic bacteria. Colloids Surf. B Biointerfaces, 2020, 185110627
[http://dx.doi.org/10.1016/j.colsurfb.2019.110627] [PMID: 31732391]
[27]
Rutherford, S.T.; Bassler, B.L. Bacterial quorum sensing: its role in virulence and possibilities for its control. Cold Spring Harb. Perspect. Med., 2012, 2(11)a012427
[http://dx.doi.org/10.1101/cshperspect.a012427] [PMID: 23125205]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy