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Photoresponsive cyclometalated gold (III) hydride, preparation method and applications thereof

A ring metal, photoresponsive technology, applied in the field of medicine and chemical industry, can solve the problems of reducing efficiency and selectivity, and achieve good selectivity effect

Inactive Publication Date: 2020-04-14
SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, since gold(I) and gold(III) also selectively target proteins or enzymes containing thiol (cysteine) or selenol (selenocysteine) structures, the thiol / selenium-containing Alcohol-enzymes (e.g., thioredoxin reductase, TrxR) have high inhibitory activity, but off-target binding of non-neoplastic thiol compounds (e.g., serum albumin, glutathione, etc.) greatly reduces their efficiency and selectivity sex

Method used

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  • Photoresponsive cyclometalated gold (III) hydride, preparation method and applications thereof
  • Photoresponsive cyclometalated gold (III) hydride, preparation method and applications thereof
  • Photoresponsive cyclometalated gold (III) hydride, preparation method and applications thereof

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0041] The preparation of embodiment 1 compound I-1

[0042] The specific preparation process of compound Ⅰ-1 is as follows:

[0043]

[0044] (1) Reflux the mixture of ligand 1-2 (1~2g) and mercuric acetate (1.5 equivalents) in absolute ethanol (30mL) for 48 hours, then cool to room temperature, dropwise add chloroform chloride dissolved in hot ethanol Lithium; the white suspension was refluxed for an additional 2 h; after cooling to room temperature, the precipitate was filtered and redissolved in dichloromethane; after removal of insoluble impurities, the solvent of the filtrate was removed under reduced pressure and the crude product was used without further purification 1-3.

[0045] (2) the crude product 1-3 and KAuCl 4 (1 eq.) of the mixture was refluxed in acetonitrile (40 mL) for 48 hours. After cooling to room temperature, a pale yellow / white precipitate was filtered, washed several times with acetonitrile and water, then washed with ether and air-dried to give ...

Embodiment 2

[0052] Test the reaction of the compound with sulfhydryl groups. Taking compound I-1 as an example, test whether it reacts with N-acetylcysteine ​​(NAC) under dark and light conditions. The specific test process is: 100μM compound I-1 with 10mM N-acetylcysteine ​​(NAC) in DMSO-d 6 Mix in medium and place it in the dark for 72 hours. During the standing process, samples were taken every 24 hours for nuclear magnetic detection; after 72 hours, they were irradiated at 420nm, starting from the light, until 5 minutes, 10 minutes, 20 minutes and 30 minutes of light, and the samples were tested by LC. track.

[0053] The NMR test results under dark conditions are as follows: figure 1 As shown, the LC tracking results after illumination are as follows figure 2 shown.

[0054] from figure 1 It can be seen from the figure that after compound I-1 was mixed with N-acetylcysteine ​​(NAC), the nuclear magnetic spectrum did not change within 72 hours, indicating that no reaction occurre...

Embodiment 3

[0057] Taking compound I-2 as an example, test its inhibitory activity on purified TrxR enzyme, the test process is as follows:

[0058] Recombinant human TrxR1 (ICMO Corp, Sweden; 20 nM) was reduced with NADPH (0.2 mM), and then the compound to be tested (i.e. compound I-2) (0-100 nM ), [C^N^C-Au-PPh 3 ]OTf (0-100nM) or C^N^C-Au-NHC(n-Bu)OTf (0-100nM) was added to 2μL TrxR (0.92nM), and the experimental group that did not need light was incubated for 1h and then directly added 5,5 '-Dithiobis(2-nitrobenzoic acid) (DTNB, final 3mM) initiated the reaction and then carried out the determination of OD410nm, the TrxR activity was calculated by the increase rate of the initial OD410nm; for the experimental group requiring light, After incubation for 1 hour and 5 minutes of light, 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB, final 3 mM) was added to initiate the reaction, and then the OD 410 nm was measured. where [C^N^C-Au-PPh 3 ]OTf is a positive control, and C^N^C-Au-NHC(n-Bu)OT...

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Abstract

The invention discloses a photoresponsive cyclometalated gold (III) hydride, a preparation method and applications thereof, wherein the structure of the compound is represented by a formula (I), and R<1>, R<2> and R<3> are respectively and independently one or a plurality of materials selected from hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 halogenated alkyl, C1-4 halogenated alkoxy, C1-4 alkyl alcohol group, phenyl and halogenated phenyl. According to the invention, the cyclometalated gold (III) hydride has photoactivation performance; under a dark condition, the IC50 values of the cyclometalated gold (III) hydride to HCT116 human colon cancer cells, A549 human lung cancer cells, MCF-7 human breast cancer cells, HepG-2 human hepatoma carcinoma cells and LO2 human liver normal cells are greater than 100 [mu]M; and under an illumination condition, the photoresponsive cyclometalated gold (III) hydride induces cancer cell death, inhibits cancer cell proliferation, inhibits thioredoxin reductase and inhibits zebra fish vascular growth, has excellent inhibition effects on the four kinds of cancer cells, has the inhibition effect obviously superior to cis-platinum, and can be used as an anti-cancer drug.

Description

technical field [0001] The invention relates to the technical field of medicine and chemical industry, and more specifically, to a photoresponsive cyclometallic gold (III) hydride and a preparation method and application thereof. Background technique [0002] Cisplatin anticancer drugs will cause strong adverse reactions in patients, such as bone marrow suppression, gastrointestinal reactions, renal toxicity, neurotoxicity, allergic reactions, electrolyte disturbances and liver damage. Moreover, since cisplatin and its modified complexes commonly used in the market currently have no targeting when acting on the human body, it causes strong adverse reactions to the human body. Moreover, due to the increase in the dosage, the sensitivity of cancer cells to the drug is significantly decreased. Therefore, there is an urgent need to develop new and selective anticancer drugs. [0003] It has been reported that gold (III) and gold (I) complexes exhibit very good anti-proliferati...

Claims

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Application Information

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IPC IPC(8): C07F1/12A61P35/00
CPCA61P35/00C07F1/12
Inventor 邹滔滔罗和江陈新滋
Owner SUN YAT SEN UNIV
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