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Application of isothiocyanates in preparing glutathione reductase inhibitor

A technology of isothiocyanate and benzyl isothiocyanate, which is applied in the application field of isothiocyanate in the preparation of glutathione reductase inhibitors, can solve the problem of limited application, poor selectivity, and complicated chemical synthesis and other problems, to achieve the effects of low risk of side effects, strong inhibitory ability, and high inhibitory activity

Pending Publication Date: 2020-02-07
ZHEJIANG CANCER HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] There are many known GR inhibitors, including gold-phospholene, naphthoquinone acid, allicene, methylene blue, xanthines, cadmium ions, S-nitrosoglutathione, arsenic-containing compounds and thiol uric acid, etc., but these GR inhibitors have disadvantages such as low inhibition efficiency, poor selectivity, poor stability and complex chemical synthesis
At present, the most commonly used GR inhibitor is 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), and the IC measured in its inhibition experiment on yeast GR 50 It is 646μM, which can specifically inhibit glutathione reductase, but this inhibition is accompanied by toxicity caused by other non-specific interactions (such as inhibition of DNA synthesis). Some literatures believe that the cytotoxicity of BCNU limits its use as a chemotherapy enhancer Applications

Method used

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  • Application of isothiocyanates in preparing glutathione reductase inhibitor
  • Application of isothiocyanates in preparing glutathione reductase inhibitor
  • Application of isothiocyanates in preparing glutathione reductase inhibitor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0046] Example 1 The inhibitory effect of benzyl isothiocyanate (BITC) on glutathione reductase (GR)

[0047] 1. Determination of the inhibitory rate of benzyl isothiocyanate to purified yeast GR activity in vitro

[0048] Dissolve benzyl isothiocyanate in dimethyl sulfoxide (DMSO) to make a 100mM stock solution, then dilute it with phosphate buffer (100mM, 2mM EDTA, pH 7.0) to make a 0.5mM benzyl isothiocyanate working solution ,stand-by.

[0049] Yeast GR was placed in phosphate buffer solution (100mM, 2mM EDTA, pH 7.0) containing 1mg / mL bovine serum albumin (BSA) and 0.2mM NADPH, and prepared into 6U / mL yeast GR working solution, ready for use.

[0050] The experimental process of treating yeast GR with different concentrations of benzyl isothiocyanate for 1 hour is as follows: a certain volume of 6 U / mL yeast GR working solution was placed in different microwells of a 96-well plate, and a certain volume of 0.5mM benzyl isothiocyanate working solution, adjust the total vo...

Embodiment 2

[0084] Example 2 Inhibition of phenylethyl isothiocyanate (PEITC) to glutathione reductase (GR) 1. Measurement of the inhibitory rate of phenylethyl isothiocyanate to purified yeast GR activity in vitro

[0085] Dissolve phenylethyl isothiocyanate in dimethyl sulfoxide (DMSO) to make a 100mM stock solution, then dilute it with phosphate buffer (100mM, 2mM EDTA, pH 7.0) to make 0.5mM phenylethyl isothiocyanate Working fluid, ready for use.

[0086] Yeast GR was placed in phosphate buffer solution (100mM, 2mM EDTA, pH 7.0) containing 1mg / mL bovine serum albumin (BSA) and 0.2mM NADPH, and prepared into 6U / mL yeast GR working solution, ready for use.

[0087] The experimental process of treating yeast GR with different concentrations of phenylethyl isothiocyanate for 1 hour is as follows: put a certain volume of 6 U / mL yeast GR working solution in different microwells of a 96-well plate, and add a certain volume of 0.5mM phenylethyl isothiocyanate working solution, adjust the tot...

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Abstract

The present invention discloses an application of isothiocyanates in preparing a glutathione reductase inhibitor. Two isothiocyanates extracted from natural materials are firstly used to treat purified yeast glutathione reductase and human tumor cells. The two isothiocyanates can effectively inhibit activity of the purified yeast glutathione reductase and glutathione reductase in the human tumor cells, and inhibitory effects of the two isothiocyanates on glutathione reductase activity are significantly stronger than that of artificially synthetic p-benzene diisothiocyanate. On the basis, the two isothiocyanates are firstly provided to be used as effective ingredients or active ingredients for preparing the glutathione reductase inhibitor which can also be further used as an antitumor agentand a tool compound for studying glutathione reductase characteristics.

Description

technical field [0001] The invention belongs to the fields of biomedicine and pharmacy, and in particular relates to the application of isothiocyanates in the preparation of glutathione reductase inhibitors. Background technique [0002] Glutathione is the most common non-protein molecule in cells, and it participates in various intracellular activities, including maintenance of intracellular redox state, detoxification and metabolism of exogenous substances, intracellular signal transduction and gene regulation, etc. Glutathione mainly exists in cells in the form of reduced glutathione (GSH), and the ratio of oxidized glutathione (glutathione disulfide, GSSG) to reduced glutathione is about 1: 100, while the higher intracellular level of reduced glutathione mainly depends on the efficient catalytic reduction of oxidized glutathione by glutathione reductase (GR). [0003] Glutathione reductase is a flavin enzyme that can catalyze the reduction of oxidized glutathione to red...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/26A61P35/00A61P33/06
CPCA61K31/26A61P35/00A61P33/06
Inventor 陈巍李夏
Owner ZHEJIANG CANCER HOSPITAL