Genomics & Informatics

Korea Genome Organization (한국유전체학회)
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Antibacterial and Pharmacological Evaluation of Fluoroquinolones: A Chemoinformatics Approach

  • Sood, Damini (Drug Discovery & Development Laboratory, Department of Chemistry, University of Delhi) ;
  • Kumar, Neeraj (Drug Discovery & Development Laboratory, Department of Chemistry, University of Delhi) ;
  • Singh, Aarushi (Drug Discovery & Development Laboratory, Department of Chemistry, University of Delhi) ;
  • Sakharkar, Meena Kishore (College of Pharmacy and Nutrition, University of Saskatchewan) ;
  • Tomar, Vartika (Drug Discovery & Development Laboratory, Department of Chemistry, University of Delhi) ;
  • Chandra, Ramesh (Drug Discovery & Development Laboratory, Department of Chemistry, University of Delhi)
  • Received : 2018.04.04
  • Accepted : 2018.05.03
  • Published : 2018.09.30
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Abstract

Fluoroquinolone (FQ) antibiotics are an important class of synthetic antibacterial agents. These are the most extensively used drugs for treating bacterial infections in the field of both human and veterinary medicine. Herein, the antibacterial and pharmacological properties of four fluoroquinolones: lomefloxacin, norfloxacin, ciprofloxacin, and ofloxacin have been studied. The objective of this study was to analyze the antibacterial characteristics of the different fluoroquinolones. Also, the pharmacological properties of the compounds including the Lipinski rule of five, absorption, distribution, metabolism, and excretion, LD50, drug likeliness, and toxicity were evaluated. We found that among all four FQ molecules, ofloxacin showed the highest antibacterial activity through in silico assays with a strong interaction (-38.52 kJ/mol) with the antibacterial target protein (topoisomerase-II DNA gyrase enzyme). The pharmacological and pharmacokinetic analysis also showed that the compounds ciprofloxacin, ofloxacin, lomefloxacin and norfloxacin have good pharmacological properties. Notably, ofloxacin was found to possess an IGC50 (concentration needed to inhibit 50% growth) value of $0.286{\mu}g/L$ against the Tetrahymena pyriformis protozoa. It also tested negative for the Ames toxicity test, showing its non-carcinogenic character.

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References

  1. Aldred KJ, McPherson SA, Turnbough CL Jr, Kerns RJ, Osheroff N. Topoisomerase IV-quinolone interactions are mediated through a water-metal ion bridge: mechanistic basis of quinolone resistance. Nucleic Acids Res 2013;41:4628-4639. https://doi.org/10.1093/nar/gkt124
  2. Crumplin GC, Kenwright M, Hirst T. Investigations into the mechanism of action of the antibacterial agent norfloxacin. J Antimicrob Chemother 1984;13 Suppl B:9-23.
  3. Nicolle LE. Management of acute uncomplicated pyelonephritis. In: Urinary Tract Infections (Bergan T, ed.). Basel: Karger, 1997. pp. 8-13.
  4. Owens RC Jr, Ambrose PG. Clinical use of the fluoroquinolones. Med Clin North Am 2000;84:1447-1469. https://doi.org/10.1016/S0025-7125(05)70297-2
  5. Appelbaum PC. Quinolone activity against anaerobes: microbiological aspects. Drugs 1995;49 Suppl 2:76-80. https://doi.org/10.2165/00003495-199500492-00012
  6. King DE, Malone R, Lilley SH. New classification and update on the quinolone antibiotics. Am Fam Physician 2000;61:2741-2748.
  7. Sharma PC, Jain A, Jain S, Pahwa R, Yar MS. Ciprofloxacin: review on developments in synthetic, analytical, and medicinal aspects. J Enzyme Inhib Med Chem 2010;25:577-589. https://doi.org/10.3109/14756360903373350
  8. Davis H, McGoodwin E, Reed TG. Anaphylactoid reactions reported after treatment with ciprofloxacin. Ann Intern Med 1989;111:1041-1043. https://doi.org/10.7326/0003-4819-111-12-1041
  9. World Health Organization. WHO Model List of Essential Medicines. 19th list. Geneva: World Health Organization, 2015.
  10. Wadworth AN, Goa KL. Lomefloxacin. A review of its anti- bacterial activity, pharmacokinetic properties and therapeutic use. Drugs 1991;42:1018-1060. https://doi.org/10.2165/00003495-199142060-00009
  11. Barza M. Use of quinolones for treatment of ear and eye infections. Eur J Clin Microbiol Infect Dis 1991;10:296-303. https://doi.org/10.1007/BF01967003
  12. Cox CE. Ofloxacin in the management of complicated urinary tract infections, including prostatitis. Am J Med 1989;87:61S-68S. https://doi.org/10.1016/S0002-9343(89)80932-5
  13. DuPont HL. Guidelines on acute infectious diarrhea in adults. The Practice Parameters Committee of the American College of Gastroenterology. Am J Gastroenterol 1997;92:1962-1975.
  14. Gadade DD, Sarda K, Shahi SR. Investigation and optimization of the effect of polymers on drug release of nor- floxacin from floating tablets. Polim Med 2016;46:117-127.
  15. Nagaraja V, Godbole AA, Henderson SR, Maxwell A. DNA topoisomerase I and DNA gyrase as targets for TB therapy. Drug Discov Today 2017;22:510-518. https://doi.org/10.1016/j.drudis.2016.11.006
  16. Alves MJ, Froufe HJ, Costa AF, Santos AF, Oliveira LG, Osorio SR, et al. Docking studies in target proteins involved in antibacterial action mechanisms: extending the knowledge on standard antibiotics to antimicrobial mushroom compounds. Molecules 2014;19:1672-1684. https://doi.org/10.3390/molecules19021672
  17. Kumar N, Tomar R, Pandey A, Tomar V, Singh VK, Chandra R. Preclinical evaluation and molecular docking of 1,3-benzodioxole propargyl ether derivatives as novel inhibitor for combating the histone deacetylase enzyme in cancer. Artif Cells Nanomed Biotechnol 2018;46:1288-1299. https://doi.org/10.1080/21691401.2017.1369423
  18. Singh V, Kumar N, Chandra R. Structural insights of induced pluripotent stem cell regulatory factors Oct4 and its interaction with Sox2 and Fgf4 gene. Adv Biotechnol Biochem 2017; (5):J119.
  19. Bax BD, Chan PF, Eggleston DS, Fosberry A, Gentry DR, Gorrec F, et al. Type IIA topoisomerase inhibition by a new class of antibacterial agents. Nature 2010;466:935-940. https://doi.org/10.1038/nature09197
  20. Vriend G. WHAT IF: a molecular modeling and drug design program. J Mol Graph 1990;8:52-56, 29. https://doi.org/10.1016/0263-7855(90)80070-V
  21. Lovell SC, Davis IW, Arendall WB 3rd, de Bakker PI, Word JM, Prisant MG, et al. Structure validation by Calpha geometry: phi, psi and Cbeta deviation. Proteins 2003;50:437-450. https://doi.org/10.1002/prot.10286
  22. Luthy R, Bowie JU, Eisenberg D. Assessment of protein models with three-dimensional profiles. Nature 1992;356:83-85. https://doi.org/10.1038/356083a0
  23. Ghoorah AW, Devignes MD, Smaïl-Tabbone M, Ritchie DW. Protein docking using case-based reasoning. Proteins 2013;81: 2150-2158. https://doi.org/10.1002/prot.24433
  24. Goddard TD, Huang CC, Ferrin TE. Visualizing density maps with UCSF Chimera. J Struct Biol 2007;157:281-287. https://doi.org/10.1016/j.jsb.2006.06.010
  25. Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and per- meability in drug discovery and development settings. Adv Drug Deliv Rev 2001;46:3-26. https://doi.org/10.1016/S0169-409X(00)00129-0
  26. Daina A, Michielin O, Zoete V. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep 2017;7: 42717. https://doi.org/10.1038/srep42717
  27. ACD-I Lab. Toronto: Advanced Chemistry Development, Inc., 2015. Accessed 2018 May 2. Available from: http://www.acdlabs.com.
  28. Lagorce D, Maupetit J, Baell J, Sperandio O, Tufféry P, Miteva MA, et al. The FAF-Drugs2 server: a multistep engine to prepare electronic chemical compound collections. Bioinformatics 2011;27:2018-2020. https://doi.org/10.1093/bioinformatics/btr333