Method for designing copper carrier anti-cancer reagent based on oxidation reduction cycle strategy

A design method and carrier technology, applied in the field of chemical medicine, to achieve the effect of good innovation, broad application prospects and good application

Active Publication Date: 2018-12-21
LANZHOU UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0004] At present, there have been reports on the development of anticancer drugs using the above two strategies, but there is no method to design a regenerative carri

Method used

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  • Method for designing copper carrier anti-cancer reagent based on oxidation reduction cycle strategy
  • Method for designing copper carrier anti-cancer reagent based on oxidation reduction cycle strategy
  • Method for designing copper carrier anti-cancer reagent based on oxidation reduction cycle strategy

Examples

Experimental program
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Effect test

Embodiment 1

[0024] Embodiment 1: A kind of method for designing copper carrier anticancer reagent based on redox cycle strategy, comprises the following steps:

[0025] (1) Determination of intracellular copper ion concentration.

[0026] The concentration of copper ions in the cells increased, indicating that DPY can carry copper ions into the cells.

[0027] The present invention examines DPY and CuCl 2 Copper ion uptake in tumor cells after co-acting, if DPY is used as a copper ion carrier, Cu 2+ loaded into the cell, then the intracellular Cu 2+ content will increase. We set up four groups of experiments: blank control group; 20μM CuCl 2 group; 20 μM CuCl 2 Combined with 20μM DPY; 20μM CuCl 2 Combined with 20 μ M DPH group. The above grouped drugs were added to HepG2 cells, and after 0, 0.5, 1, 3, 6, 12, 24 and 48 hours of action, the cells were collected for quantification, and the intracellular levels were detected by inductively coupled plasma atomic emission spectrometry (I...

example 1

[0028] Operation method of instance 1:

[0029] HepG2 or HeLa cells (1-3×10 6 ) were planted in triplicate in a 100mm culture dish overnight to adhere to the wall, and the drug was added at a specified concentration for a specified time, and the cells were collected. One was used for protein quantification; the other two were used for copper ion concentration detection: the sample was dissolved in concentrated nitric acid, and the copper content was detected by inductively coupled plasma atomic emission spectrometry (ICP-AES).

Embodiment 2

[0030] Embodiment 2: A method for designing copper-carrier anticancer agents based on a redox cycle strategy, comprising the following steps:

[0031] (1) Determination of intracellular copper ion concentration.

[0032] The increase in the concentration of copper ions in the cells indicates that DPY can carry copper ions into the cells as in Example 1.

[0033] (2) Determination of total sulfhydryl levels in cells.

[0034] The level of sulfhydryl groups in the cells decreased, indicating that small molecule thiols were involved in this cycle reaction.

[0035] As described in Example 1, DPY can load copper ions into cells. Under the action of intracellular reducing sulfhydryl molecules, Cu will be released 2+, then the content of small molecule sulfhydryl groups in the cells will inevitably decrease, so the present invention detects the changes in the level of total sulfhydryl molecules in the cells, as shown in Figure 3A-C, respectively with 20 μM CuCl 2 , 20μM DPY and ...

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Abstract

The invention aims at providing a method for designing copper carrier anti-cancer reagent based on an oxidation reduction cycle strategy. Through taking advantage of oxidation reduction characteristics of a cancer cell, with participation of two antioxidant systems including thioredoxin and glutathione in the cell, an aim of carrier splitting, regeneration and carrying of a copper ion in the cellis realized through smartly taking advantage of interaction among small molecular mercaptan, the copper carrier and the copper ion. Compared with the conventional method, the method provided by the invention has very high efficiency of transporting the copper ion and has wide application foreground.

Description

technical field [0001] The invention relates to the field of chemistry and medicine, in particular to a method for designing a copper carrier anticancer agent based on a redox cycle strategy. Background technique [0002] Compared with normal cells, cancer cells exhibit increased levels of reactive oxygen species (ROS) to sustain their malignant phenotypic growth, thereby relying more on mechanisms of "redox adaptation" that maintain ROS levels within a range that allows them to escape death (NatRev Drug Discov., 2013, 12(12): 931-947). Based on this biochemical difference, it provides a new method for the design of anticancer reagents. [0003] The copper level in cancer cells is significantly higher than that in normal cells (Cancer Treat Rev., 2009, 35(1): 32-46). When the intracellular copper concentration is increased, the treatment between normal cells and cancer cells The window makes it possible to develop copper ionophore anticancer drugs (Chem Rev., 2014, 114(1):...

Claims

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Application Information

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IPC IPC(8): G01N33/68G01N21/73G01N21/31G01N21/64G01N15/14G01N30/02
CPCG01N15/14G01N21/31G01N21/6428G01N21/73G01N30/02G01N33/68G01N2021/6439
Inventor 张军民房建国
Owner LANZHOU UNIVERSITY
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