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Frontiers of Chemical Science and Engineering

ISSN 2095-0179

ISSN 2095-0187(Online)

CN 11-5981/TQ

Postal Subscription Code 80-969

2018 Impact Factor: 2.809

Front. Chem. Sci. Eng.    2018, Vol. 12 Issue (2) : 311-314    https://doi.org/10.1007/s11705-017-1697-0
COMMUNICATION
A simple umbelliferone based fluorescent probe for the detection of nitroreductase
Adam C. Sedgwick1, Alex Hayden2, Barry Hill2, Steven D. Bull1, Robert B. P. Elmes2(), Tony D. James1()
1. Department of Chemistry, University of Bath, Bath, BA2 7AY, UK
2. Department of Chemistry, Maynooth University, Maynooth, Co. Kildare, Ireland
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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.

Corresponding Author(s): Robert B. P. Elmes,Tony D. James   
Just Accepted Date: 30 November 2017   Online First Date: 15 January 2018    Issue Date: 09 May 2018
 Cite this article:   
Adam C. Sedgwick,Alex Hayden,Barry Hill, et al. A simple umbelliferone based fluorescent probe for the detection of nitroreductase[J]. Front. Chem. Sci. Eng., 2018, 12(2): 311-314.
 URL:  
https://academic.hep.com.cn/fcse/EN/10.1007/s11705-017-1697-0
https://academic.hep.com.cn/fcse/EN/Y2018/V12/I2/311
Fig.1  Scheme 1 Synthesis of NCOU1
Fig.2  Photograph of (a) NCOU1, (b) umbelliferone, and (c) NCOU1+ NTR
Fig.3  Fluorescence spectra of NCOU1 (10 µmol/L) with the addition of nitroreductase (8 µg/mL) and NADH (500 µmol/L) and measured over 60 min in 10 mmol/L PBS (pH 7.4). lex = 315 nm
Fig.4  Dose-response time curve of NCOU1 (10 µmol/L) with additions of nitroreductase (0, 0.5, 1, 4 and 8 µg/mL) and NADH (500 µmol/L in 10 mmol/L PBS (pH 7.4)). lex = 315 nm
Fig.5  Selectivity bar chart of NCOU1 (10 µmol/L) with addition of A (nitroreductase, 1 µg/mL), B (nitroreductase and dicoumarol, 1 µg/mL), C (DT-diaphorase, 1 µg/mL) and D (blank). All measurements contained NADH (500 µmol/L) in 10 mmol/L PBS (pH 7.4) lex = 315 nm (lem = 455 nm)
1 Brown J M, Wilson W R. Exploiting tumour hypoxia in cancer treatment. Nature Reviews. Cancer, 2004, 4(6): 437–447
https://doi.org/10.1038/nrc1367
2 Wilson W R, Hay M P. Targeting hypoxia in cancer therapy. Nature Reviews. Cancer, 2011, 11(6): 393–410
https://doi.org/10.1038/nrc3064
3 Denny W A. Prodrug strategies in cancer therapy. European Journal of Medicinal Chemistry, 2001, 36(7-8): 577–595
https://doi.org/10.1016/S0223-5234(01)01253-3
4 Elmes R B P. Bioreductive fluorescent imaging agents: Applications to tumour hypoxia. Chemical Communications, 2016, 52(58): 8935–8956
https://doi.org/10.1039/C6CC01037G
5 Pacheco-Torres J, López-Larrubia P, Ballesteros P, Cerdán S. Imaging tumor hypoxia by magnetic resonance methods. NMR in Biomedicine, 2011, 24(1): 1–16
https://doi.org/10.1002/nbm.1558
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): 7893–7943
https://doi.org/10.1021/cr500553d
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): 4563–4601
https://doi.org/10.1039/C4CS00051J
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): 6418–6436
https://doi.org/10.1039/c0cc00686f
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): 2554–2556
https://doi.org/10.1039/c3cc38980d
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): 2058–2062
https://doi.org/10.1002/asia.201402364
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): 56207–56210
https://doi.org/10.1039/C4RA10044A
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): 4440–4442
https://doi.org/10.1039/C4CC10345A
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): 574–581
https://doi.org/10.1039/C4AN01934B
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): 2719–2724
https://doi.org/10.1002/asia.201600012
15 Jin C, Zhang Q, Lu W. Selective turn-on near-infrared fluorescence probe for hypoxic tumor cell imaging. RSC Advances, 2017, 7(30): 18217–18223
https://doi.org/10.1039/C7RA01466J
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): 4383–4389
https://doi.org/10.1039/C7OB00781G
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): 345–350
https://doi.org/10.1039/C6AN02107G
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): 928–931
https://doi.org/10.1021/ol102975t
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): 14739–14741
https://doi.org/10.1039/C5CC05518K
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): 12009–12012
https://doi.org/10.1021/jacs.6b06229
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: 112–116
https://doi.org/10.1016/j.bios.2014.07.024
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]-3H-phenoxazin-3-one. Analytical Chemistry, 2013, 85(8): 3926–3932
https://doi.org/10.1021/ac400750r
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): 5859–5861
https://doi.org/10.1039/c3cc42610f
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): 2918–2923
https://doi.org/10.1002/asia.201600945
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): 6104–6108
https://doi.org/10.1039/C7OB01406F
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): 12350–12352
https://doi.org/10.1039/C6CC06829D
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): 3368–3373
https://doi.org/10.1039/C4SC01417K
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, Zhu W 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): 5334–5340
https://doi.org/10.1021/jacs.6b01705
29 Li M, Wu X M, Wang Y, Li Y S, Zhu W H, James T D. A near-infrared colorimetric fluorescent chemodosimeter for the detection of glutathione in living cells. Chemical Communications, 2014, 50(14): 1751–1753
https://doi.org/10.1039/c3cc48128j
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): 10441–10443
https://doi.org/10.1039/C7CC05872A
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): 12822–12825
https://doi.org/10.1039/C7CC07845E
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): 528–531
https://doi.org/10.1021/acs.orglett.6b03695
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): 525–528
https://doi.org/10.1039/C6CC08971B
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