A simple umbelliferone based fluorescent probe for the detection of nitroreductase

Communication

Abstract

A simple nitrobenzyl-umbelliferone (NCOU1) was synthesised containing a nitroreductase (NTR) trigger moiety. The presence of NTR, resulted in the fragmentation of the parent molecule and release of the highly emissive fluorophore umbelliferone via an NTR-catalyzed reduction of the nitro group. In the presence of the NTR enzyme, NCOU1 gave rise to a 5-fold increase in fluorescence intensity at 455 nm and was selective for NTR over other reductive enzymes. These results indicate that NCOU1 can be used as a simple assay for the detection of NTR.

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Notes

Acknowledgements

We would like to thank the EPSRC and the University of Bath for funding. TDJ wishes to thank the Royal Society for a Wolfson Research Merit Award. ACS thanks the EPSRC for his studentship. RBPE acknowledges support funding from Maynooth University. NMR characterisation facilities were provided through the Chemical Characterisation and Analysis Facility (CCAF) at the University of Bath (www.bath.ac.uk/ccaf). All data supporting this study are provided as supplementary information accompanying this paper.

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A simple umbelliferone based fluorescent probe for the detection of nitroreductase

References

  1. 1.
    Brown J M, Wilson W R. Exploiting tumour hypoxia in cancer treatment. Nature Reviews. Cancer, 2004, 4(6): 437–447CrossRefGoogle Scholar
  2. 2.
    Wilson W R, Hay M P. Targeting hypoxia in cancer therapy. Nature Reviews. Cancer, 2011, 11(6): 393–410CrossRefGoogle Scholar
  3. 3.
    Denny W A. Prodrug strategies in cancer therapy. European Journal of Medicinal Chemistry, 2001, 36(7-8): 577–595CrossRefGoogle Scholar
  4. 4.
    Elmes R B P. Bioreductive fluorescent imaging agents: Applications to tumour hypoxia. Chemical Communications, 2016, 52(58): 8935–8956CrossRefGoogle Scholar
  5. 5.
    Pacheco-Torres J, López-Larrubia P, Ballesteros P, Cerdán S. Imaging tumor hypoxia by magnetic resonance methods. NMR in Biomedicine, 2011, 24(1): 1–16CrossRefGoogle Scholar
  6. 6.
    Wu J, Kwon B, Liu W, Anslyn E V, Wang P, Kim J S. Chromogenic/fluorogenic ensemble chemosensing systems. Chemical Reviews, 2015, 115(15): 7893–7943CrossRefGoogle Scholar
  7. 7.
    Yang Z, Cao J, He Y, Yang J H, Kim T, Peng X, Kim J S. Macro-/micro-environment-sensitive chemosensing and biological imaging. Chemical Society Reviews, 2014, 43(13): 4563–4601CrossRefGoogle Scholar
  8. 8.
    Qian X, Xiao Y, Xu Y, Guo X, Qian J, Zhu W. “Alive” dyes as fluorescent sensors: Fluorophore, mechanism, receptor and images in living cells. Chemical Communications, 2010, 46(35): 6418–6436CrossRefGoogle Scholar
  9. 9.
    Xu K, Wang F, Pan X, Liu R, Ma J, Kong F, Tang B. High selectivity imaging of nitroreductase using a near-infrared fluorescence probe in hypoxic tumor. Chemical Communications, 2013, 49(25): 2554–2556CrossRefGoogle Scholar
  10. 10.
    Wan Q Q, Gao X H, He X Y, Chen S M, Song Y C, Gong Q Y, Li X H, Ma H M. A cresyl violet-based fluorescent off-on probe for the detection and imaging of hypoxia and nitroreductase in living organisms. Chemistry, an Asian Journal, 2014, 9(8): 2058–2062CrossRefGoogle Scholar
  11. 11.
    Yuan J, Xu Y Q, Zhou N N, Wang R, Qian X H, Xu Y F. A highly selective turn-on fluorescent probe based on semi-cyanine for the detection of nitroreductase and hypoxic tumor cell imaging. RSC Advances, 2014, 4(99): 56207–56210CrossRefGoogle Scholar
  12. 12.
    Wong R H F, Kwong T, Yau K H, Au-Yeung H Y. Real time detection of live microbes using a highly sensitive bioluminescent nitroreductase probe. Chemical Communications, 2015, 51(21): 4440–4442CrossRefGoogle Scholar
  13. 13.
    Xu J, Sun S, Li Q, Yue Y, Li Y, Shao S. A rapid response “turn-on” fluorescent probe for nitroreductase detection and its application in hypoxic tumor cell imaging. Analyst (London), 2015, 140(2): 574–581CrossRefGoogle Scholar
  14. 14.
    Zhou J, Shi W, Li L H, Gong Q Y, Wu X F, Li X H, Ma H M. A lysosome-targeting fluorescence off-on probe for imaging of nitroreductase and hypoxia in live cells. Chemistry, an Asian Journal, 2016, 11(19): 2719–2724CrossRefGoogle Scholar
  15. 15.
    Jin C, Zhang Q, Lu W. Selective turn-on near-infrared fluorescence probe for hypoxic tumor cell imaging. RSC Advances, 2017, 7(30): 18217–18223CrossRefGoogle Scholar
  16. 16.
    Huang B, Chen W, Kuang Y Q, Liu W, Liu X J, Tang L J, Jiang J H. A novel off-on fluorescent probe for sensitive imaging of mitochondria-specific nitroreductase activity in living tumor cells. Organic & Biomolecular Chemistry, 2017, 15(20): 4383–4389CrossRefGoogle Scholar
  17. 17.
    Zhou Y, Bobba K N, Lv X W, Yang D, Velusamy N, Zhang J F, Bhuniya S. A biotinylated piperazine-rhodol derivative: A ‘turn-on’ probe for nitroreductase triggered hypoxia imaging. Analyst (London), 2017, 142(2): 345–350CrossRefGoogle Scholar
  18. 18.
    Cui L, Zhong Y, Zhu W, Xu Y, Du Q, Wang X, Qian X, Xiao Y. A new prodrug-derived ratiometric fluorescent probe for hypoxia: High selectivity of nitroreductase and imaging in tumor cell. Organic Letters, 2011, 13(5): 928–931CrossRefGoogle Scholar
  19. 19.
    Cai Q, Yu T, Zhu W, Xu Y, Qian X. A turn-on fluorescent probe for tumor hypoxia imaging in living cells. Chemical Communications, 2015, 51(79): 14739–14741CrossRefGoogle Scholar
  20. 20.
    Chevalier A, Zhang Y, Khdour O M, Kaye J B, Hecht S M. Mitochondrial nitroreductase activity enables selective imaging and therapeutic targeting. Journal of the American Chemical Society, 2016, 138(37): 12009–12012CrossRefGoogle Scholar
  21. 21.
    Li Z, He X, Wang Z, Yang R, Shi W, Ma H. In vivo imaging and detection of nitroreductase in zebrafish by a new near-infrared fluorescence off-on probe. Biosensors & Bioelectronics, 2015, 63: 112–116CrossRefGoogle Scholar
  22. 22.
    Li Z, Li X, Gao X, Zhang Y, Shi W, Ma H. Nitroreductase detection and hypoxic tumor cell Imaging by a designed sensitive and selective fluorescent probe, 7-[(5-nitrofuran-2-yl)methoxy]-3Hphenoxazin- 3-one. Analytical Chemistry, 2013, 85(8): 3926–3932CrossRefGoogle Scholar
  23. 23.
    Li Z, Gao X, Shi W, Li X, Ma H. 7-((5-Nitrothiophen-2-yl) methoxy)-3H-phenoxazin-3-one as a spectroscopic off-on probe for highly sensitive and selective detection of nitroreductase. Chemical Communications, 2013, 49(52): 5859–5861CrossRefGoogle Scholar
  24. 24.
    You X, Li L, Li X, Ma H, Zhang G, Zhang D. A new tetraphenylethylene-derived fluorescent probe for nitroreductase detection and hypoxic-tumor-cell imaging. Chemistry, an Asian Journal, 2016, 11(20): 2918–2923CrossRefGoogle Scholar
  25. 25.
    Ao X, Bright S A, Taylor N C, Elmes R B P. 2-Nitroimidazole based fluorescent probes for nitroreductase; monitoring reductive stress in cellulo. Organic & Biomolecular Chemistry, 2017, 15(29): 6104–6108CrossRefGoogle Scholar
  26. 26.
    Sedgwick A C, Sun X L, Kim G, Yoon J, Bull S D, James T D. Boronate based fluorescence (ESIPT) probe for peroxynitrite. Chemical Communications, 2016, 52(83): 12350–12352CrossRefGoogle Scholar
  27. 27.
    Sun X, Xu Q, Kim G, Flower S E, Lowe J P, Yoon J, Fossey J S, Qian X, Bull S D, James T D. A water-soluble boronate-based fluorescent probe for the selective detection of peroxynitrite and imaging in living cells. Chemical Science (Cambridge), 2014, 5(9): 3368–3373CrossRefGoogle Scholar
  28. 28.
    Gu K Z, Xu Y S, Li H, Guo Z Q, Zhu S J, Zhu S Q, Shi P, James T D, Tian H, ZhuW H. Real-time tracking and in vivo visualization of beta-galactosidase activity in colorectal tumor with a ratiometric near-infrared fluorescent probe. Journal of the American Chemical Society, 2016, 138(16): 5334–5340CrossRefGoogle Scholar
  29. 29.
    Li M, Wu X M, Wang Y, Li Y S, Zhu W H, James T D. A nearinfrared colorimetric fluorescent chemodosimeter for the detection of glutathione in living cells. Chemical Communications, 2014, 50(14): 1751–1753CrossRefGoogle Scholar
  30. 30.
    Sedgwick A C, Chapman R S L, Gardiner J E, Peacock L R, Kim G, Yoon J, Bull S D, James T D. A bodipy based hydroxylamine sensor. Chemical Communications, 2017, 53(75): 10441–10443CrossRefGoogle Scholar
  31. 31.
    Sedgwick A C, Han H, Gardiner J E, Bull S D, He X P, James T D. Long-wavelength fluorescent boronate probes for the detection and intracellular imaging of peroxynitrite. Chemical Communications, 2017, 53(95): 12822–12825CrossRefGoogle Scholar
  32. 32.
    Matikonda S S, Fairhall J M, Tyndall J D A, Hook S, Gamble A B. Stability, kinetic, and mechanistic investigation of 1,8-self-immolative cinnamyl ether spacers for controlled release of phenols and generation of resonance and inductively stabilized methides. Organic Letters, 2017, 19(3): 528–531CrossRefGoogle Scholar
  33. 33.
    Kwon N, Cho M K, Park S J, Kim D, Nam S J, Cui L, Kim H M, Yoon J. An efficient two-photon fluorescent probe for human NAD (P)H: Quinone oxidoreductase (hNQO1) detection and imaging in tumor cells. Chemical Communications, 2017, 53(3): 525–528CrossRefGoogle Scholar

Copyright information

© Higher Education Press and Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Adam C. Sedgwick
    • 1
  • Alex Hayden
    • 2
  • Barry Hill
    • 2
  • Steven D. Bull
    • 1
  • Robert B. P. Elmes
    • 2
  • Tony D. James
    • 1
  1. 1.Department of ChemistryUniversity of BathBathUK
  2. 2.Department of ChemistryMaynooth UniversityMaynooth, Co. KildareIreland

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