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Radiolabeling, biological evaluation and molecular docking of delafloxacin: a novel methicillin-resistant Staphylococcus aureus infection radiotracer

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Abstract

Labeling of delafloxacin with technetium-99m (99mTc) and its characterization in terms of in vitro stability and in vitro binding with methicillin-resistant Staphylococcus aureus (MRSA) were explored. Optimum amounts of reactants were 2.5 mg delafloxacin, 125 µg stannous chloride dihydrate and ~125 MBq pertechnetate. The 99mTc-delafloxacin was stable up to 6 h. Molecular modeling and docking studies showed that the complex will stabilize the DNA-topoisomerase IIA cleavage complex and inhibit strands separation. The in vivo evaluation showed highest specific accumulation in the live MRSA model (8 %) compared to other models. All gathered data supported the usefulness of 99mTc-delafloxacin as a MRSA radiotracer.

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References

  1. Diekema D, Dodgson K, Sigurdardottir B, Pfaller M (2004) Rapid detection of antimicrobial-resistant organism carriage: an unmet clinical need. J Clin Microb 42(7):2879–2883

    Article  Google Scholar 

  2. Haque N, Bari M, Bilkis L, Haque N, Haque S, Sultana S (2011) Methicillin resistant Staphylococcus aureus—an overview. Mymensingh Med J 20(1):159–164

    CAS  Google Scholar 

  3. Rubinstein E, Kollef M, Nathwani D (2008) Pneumonia caused by methicillin-resistant Staphylococcus aureus. Clin Infect Dis 46:378–385

    Article  Google Scholar 

  4. Shah S, Khan A, Khan M (2010) Radiosynthesis and biodistribution of 99mTc-rifampicin: a novel radiotracer for in vivo infection imaging. Appl Radiat Isot 68:2255–2260

    Article  CAS  Google Scholar 

  5. El-Ghany E, Amin A, El-Kawy O, Amin M (2007) Technetium-99m labeling and freeze-dried kit formulation of levofloxacin (L-Flox): a novel agent for detecting sites of infection. J Label Compd Radiopharm 50:25–31

    Article  CAS  Google Scholar 

  6. Shah S, Khan M (2011) Radiosynthesis and characterization of the 99mTc-fleroxacin complex: a novel Escherichia coli infection imaging agent. Transit Met Chem 36:283–287

    Article  CAS  Google Scholar 

  7. Shah S, Khan A, Khan M (2011) Synthesis, biological evaluation and biodistribution of the 99mTc-garenoxacin complex in artificially infected rats. J Radioanal Nucl Chem 288:207–213

    Article  CAS  Google Scholar 

  8. Motaleb M, El-Kolaly M, Ibrahim A, El-Bary Abd (2011) A Study on the preparation and biological evaluation of 99mTc-gatifloxacin and 99mTc-cefepime complexes. J Radioanal Nucl Chem 289:57–65

    Article  CAS  Google Scholar 

  9. Shah S, Khan M (2011) Radiocomplexation and biological characterization of the 99mTcN-trovafloxacin dithiocarbamate: a novel methicillin-resistant Staphylococcus aureus infection imaging agent. J Radioanal Nucl Chem 288:215–220

    Article  CAS  Google Scholar 

  10. Akhtar M, Imran M, Nadeem M, Shahid A (2012) Antimicrobial peptides as infection imaging agents: better than radiolabeled antibiotics. Int J Peptid 2012:1–19

    Article  Google Scholar 

  11. El-Kawy O, Farah K (2015) Radiocomplexation and biological evaluation of nemonoxacin in mice infected with multiresistant Staphylococcus aureus and penicillin-resistant Streptococci. J Radioannal Nucl Chem 306:123–130

    Article  CAS  Google Scholar 

  12. Remy J, Tow-Keogh C, McConnell T, Dalton J, DeVito J (2012) Activity of delafloxacin against methicillin-resistant Staphylococcus aureus: resistance selection and characterization. J Antimicrob Chemother 67(12):2814–2820

    Article  CAS  Google Scholar 

  13. Nilius A, Shen L, Hensey-Rudloff D, Almer J, Beyer J, Balli D, Cai Y, Flamm R (2003) In vitro antibacterial potency and spectrum of ABT-492: a new fluoroquinolone. Antimicrob Agents Chemother 47:3260–3269

    Article  CAS  Google Scholar 

  14. Seral C, Carryn S, Tulkens M, Bambeke F (2003) Influence of P-glycoprotein and MRP efflux pump inhibitors on the intracellular activity of azithromycin and ciprofloxacin in macrophages infected by Listeria monocytogenes or Staphylococcus aureus. J Antimicrob Chemother 51:1167–1173

    Article  CAS  Google Scholar 

  15. Lemaire S, Tulkens P, Bambeke F (2011) Contrasting Effects of Acidic pH on the Extracellular and Intracellular Activities of the Anti-Gram-Positive Fluoroquinolones Moxifloxacin and Delafloxacin against Staphylococcus aureus. Antimicrob Agents Chemother 55(2):649–658

    Article  CAS  Google Scholar 

  16. El-Kawy O, Ibrahim I, Farah K (2015) Technetium-99m labeling and evaluation of olsalazine: a novel agent for ulcerative colitis imaging. J Label Compd Radiopharm 58:336–341

    Article  CAS  Google Scholar 

  17. El-Kawy O, Sanad M, Marzook F (2015) 99mTc-Mesalamine as potential agent for diagnosis and monitoring of ulcerative colitis: labelling, characterisation and biological evaluation. J Radioannal Nucl Chem. doi:10.1007/s10967-015-4338-4

    Google Scholar 

  18. Laponogov Sohil M, Veselkov D, Pan X, Sawhney R, Thompson A, McAuley K, Fisher L, Sanderson M (2009) Structural insight into the quinolone—DNA cleavage complex of type IIA topoisomerases. Nat Struct Mol Biol 16:667–669

    Article  CAS  Google Scholar 

  19. Shah S, Khan M (2011) 99mTc(CO)3-tosufloxacin dithiocarbamate complexation and radiobiological evaluation in male Wister rat model. J Radioanal Nucl Chem 288:485–490

    Article  CAS  Google Scholar 

  20. Shah S, Khan M (2011) Radiocharacterization of the 99mTc–rufloxacin complex and biological evaluation in Staphylococcus aureus infected rat model. J Radioanal Nucl Chem 288:373–378

    Article  CAS  Google Scholar 

  21. Bandoli G, Dolmella A, Porchia M, Tisato E, Refosco P (2001) Structural overview of technetium compounds. Coord Chem Rev 214:43–90

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Atomic Energy Authority, Cairo, 13759, Egypt

    O. A. El-kawy, A. S. Abdel-Razek & M. S. Sayed

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  1. O. A. El-kawy
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  2. A. S. Abdel-Razek
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  3. M. S. Sayed
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Correspondence to O. A. El-kawy.

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El-kawy, O.A., Abdel-Razek, A.S. & Sayed, M.S. Radiolabeling, biological evaluation and molecular docking of delafloxacin: a novel methicillin-resistant Staphylococcus aureus infection radiotracer. J Radioanal Nucl Chem 308, 1081–1088 (2016). https://doi.org/10.1007/s10967-015-4586-3

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  • DOI: https://doi.org/10.1007/s10967-015-4586-3

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