Near-infrared fluorescent probe targeting cyp1b1 enzyme and its preparation and use

A fluorescent probe, near-infrared technology, used in fluorescence/phosphorescence, preparations for in vivo tests, luminescent materials, etc., can solve the problems of difficult diagnosis and low diagnostic specificity, achieve deep non-destructive testing, promote application, Effect with application prospect and clinical translation value

Active Publication Date: 2020-07-14
SHANGHAI JIAO TONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Through near-infrared in vivo imaging of intracellular CYP1B1 enzymes, the expression site and level are displayed in vivo, providing a new method for early diagnosis of tumors, and solving the problems of difficult diagnosis and low diagnostic specificity in current tumor treatment

Method used

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  • Near-infrared fluorescent probe targeting cyp1b1 enzyme and its preparation and use
  • Near-infrared fluorescent probe targeting cyp1b1 enzyme and its preparation and use
  • Near-infrared fluorescent probe targeting cyp1b1 enzyme and its preparation and use

Examples

Experimental program
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Embodiment 1

[0037] This embodiment relates to a preparation method of near-infrared fluorescent probe I-1 derived from 6,7,10-trimethoxy-3'-fluoro-α-naphthalene flavonol with structural formula I, such as figure 1 shown, including the following steps:

[0038] Step 1: 2-(2-Aminoethoxy)ethanol (2 mmol) was dissolved in 6 mL of dichloromethane, and di-tert-butyl dicarbonyl ester (2.3 mmol) dissolved in 4 mL of dichloromethane was added dropwise under ice-cooling. After the dropwise addition, the ice bath was removed, and the reaction solution was stirred overnight at room temperature. After the reaction, the reaction solution was diluted with 10 mL of dichloromethane, and the organic phase was washed successively with an equal volume of water, saturated sodium bicarbonate solution and saturated sodium chloride solution. After drying the organic phase with anhydrous sodium sulfate, it was concentrated under reduced pressure to obtain a colorless oily substance tert-butoxyacyl 2-(2-hydroxyet...

Embodiment 2

[0044] This embodiment relates to a preparation method of near-infrared fluorescent probe I-2 derived from 6,7,10-trimethoxy-3'-fluoro-α-naphthalene flavonol with structural formula I, such as figure 1 shown, including the following steps:

[0045] Step 1: Same as Step 1 of Example 1, with 2-(2-(2-aminoethoxy)ethoxy)ethanol instead of 2-(2-aminoethoxy)ethanol to obtain a colorless oily tert-butoxy Acyl 2-(2-(2-hydroxyethoxy)ethoxy)ethylamine II-2 (n=2), yield: 98%. 1 HNMR (400MHz, CDCl3 ):3.76(t, J=4.4Hz, 2H), 3.61-3.65(m, 6H), 3.56(t, J=5.2Hz, 2H), 3.32(t, J=5.2Hz, 2H), 1.45(s ,9H).

[0046] Step 2: Same as Step 2 of Example 1, substituting II-1 for II-1 to obtain colorless oily tert-butoxyacyl 2-(2-(2-iodoethoxy)ethoxy)ethylamine III -2 (n=2), yield: 70%. 1 HNMR (400MHz, CDCl 3 ):5.03(br,1H),3.76(t,J=6.8Hz,2H),3.64-3.66(m,4H),3.56(t,J=4.8Hz,2H),3.26-3.34(m,4H) ,1.45(s,9H).

[0047] Step 3: Same as step 3 of Example 1, substituting III-1 with III-2 to obtain 3'-fluoro-...

Embodiment 3

[0051] The inhibitory activity of the α-naphthoflavone derivatives V-1 and V-2 with PEG chains obtained in Examples 1 and 2 on CYP1A1, CYP1A2, and CYP1B1 enzymes was determined.

[0052] In this experiment, 7-ethoxy-3H-phenoxazine 3-keto-deethoxy (EROD) assay was used to determine its inhibitory activity and selectivity to CYP1A1, CYP1A2, and CYP1B1 enzymes (Yamaori et al, Biochem.Pharmacol.2010 ,79:1691-1698.) The reaction system (200 μL) contains CYP1A1 (10fmol), CYP1A2 (60fmol) or CYP1B1 (20fmol), different concentrations of the test compound, NADPH regeneration system (1.3mM NADPNa2, 3.3mM glucose-6-phosphate , 0.5U / ml glucose-6-phosphate-dehydrogenase), 3.3mM magnesium chloride solution and 150nM 7-ethoxy-3H-phenoxazin-3-one. Five replicate wells were set up for each experimental group or control group as a parallel experiment. The reaction buffer was 50 mM Tris-HCl (pH 7.4) buffer containing 1% BSA solution. After the reaction system was preheated at 37°C for 5 minutes...

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Abstract

The present invention provides a near-infrared fluorescent probe targeting a CYP1B1 enzyme, and preparation and use thereof. The fluorescent probe comprises an affinity ligand, a signal group, and a linking chain for linking the ligand and the signal group. The linking chain comprises a plurality of ethylene glycol fragments. The affinity ligand is an alpha-naphthoflavone derivative, and the signal group is a near infrared fluorescent molecule. The near-infrared molecular probe targeting a tumor specific marker CYP1B1 enzyme effectively avoids the influence of introduction of the signal groupon inhibitory activity for the CYP1B1 enzyme, promotes application of the near-infrared molecular probe in the tumor in-vivo imaging, and has a good application prospect and clinical transformation value in the field of early diagnosis of tumor.

Description

technical field [0001] The invention relates to the field of near-infrared in vivo imaging and molecular imaging probes, and relates to a near-infrared fluorescent probe targeting CYP1B1 enzymes and its preparation and use, specifically a near-infrared fluorescent dye and cytochrome P4501B1 The diagnostic reagent complex composed of ligands specifically bound by the enzyme can be specifically enriched in tumor cells by targeting the cytochrome P450 1B1 enzyme, and can be used for tumor-targeted fluorescence imaging and early diagnosis of tumors. Background technique [0002] In the early diagnosis and localization of tumors, non-invasive molecular imaging techniques can not only display the location of tumors through specific probes, but also reflect the changes of specific signaling molecules in tumor cells. Generally, receptors or proteins specifically expressed in tumor cells can be used as biological targets for molecular imaging, and antibodies or small molecules with h...

Claims

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Application Information

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IPC IPC(8): C07D405/14C09K11/06G01N21/64A61K49/00
CPCA61K49/0032C07D405/14C09K11/06C09K2211/1029C09K2211/1088G01N21/6486
Inventor 孟青青王增涛李绍顺董金云崔家华
Owner SHANGHAI JIAO TONG UNIV
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