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5-substituted tetrandrine compound and application thereof in preparing anticarcinogen sensitizer

A technology of tetrandrine and compounds, which can be applied in the fields of anti-tumor drugs, organic chemistry, drug combination, etc., can solve the problems that anti-tumor drugs are difficult to exert the expected effect and the like

Inactive Publication Date: 2013-01-16
FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0002] According to estimates by the American Cancer Society, more than 90% of the approximately 490,000 deaths of cancer patients each year are related to drug resistance to varying degrees. The multidrug resistance of tumor cells makes it difficult for anti-tumor drugs to exert the expected effect

Method used

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  • 5-substituted tetrandrine compound and application thereof in preparing anticarcinogen sensitizer
  • 5-substituted tetrandrine compound and application thereof in preparing anticarcinogen sensitizer
  • 5-substituted tetrandrine compound and application thereof in preparing anticarcinogen sensitizer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0068] Embodiment 1 synthesizes the compound shown in formula (I) according to the following scheme:

[0069]

[0070] Synthetic compound 1: put 1 equivalent of bromide tetrandrine, 2 equivalents of sodium azide, 10% equivalent of cuprous iodide, 30% equivalent of L-proline sodium and 30% equivalent of sodium hydroxide in a round bottom Add ethanol to the flask; react at 50°C for 4 hours, slowly add the reaction solution dropwise to 50ml of cold water while hot while stirring, a white solid precipitates out, and suction filters to obtain a white solid. TLC detection (or HPLC detection), refined in methanol.

[0071] Synthesis of compound 2: 1 equivalent of tetrandrine and 5 equivalents of cuprous cyanide were placed in a round bottom flask, and DMF was added. Replaced with inert gas for 3 times, heated to 135 degrees under the protection of inert gas (all substrates were dissolved), reacted for 5 hours, slowly added the reaction solution dropwise to 50ml of cold water whil...

Embodiment 2

[0081] Example 2 Chemotherapy Drug Doxorubicin (ADM) Effects on K562 and K562 / ADM, MCF-7 and MCF-7 / ADM Cell Proliferation

[0082] Take the K562 and K562 / ADM, MCF-7 and MCF-7 / ADM cells in the logarithmic growth phase and centrifuge, discard the supernatant, and adjust the cell number to 2×10 with RPMI1640 medium containing 10% calf serum. 4 / ml, add 96-well culture plate, add 100 μ l in every hole, each kind of cell is divided into 3 groups respectively: test group (different concentration chemotherapeutic drug ADM), negative control group (do not add medicine), blank control group (do not add cell only add culture medium). Place the 96-well plate at 37°C, 5% CO 2 In a saturated humidity incubator, after culturing for 48 hours, add 5g / L MTT20μl to each well, and after continuing to cultivate for 4 hours, add 100μl / well of triplex solution, culture over the liquid, select a wavelength of 570nm, measure the OD value on a microplate reader, and calculate Cell survival rate, IC5...

Embodiment 3

[0092] Example 3 Effect of Chemotherapeutic Drug Vincristine (VCR) on KB and KBV Cell Proliferation

[0093] Take the KB cells and KBV cells in the logarithmic growth phase and centrifuge, discard the supernatant, and adjust the cell number to 5×10 with DMEM medium containing 10% calf serum. 4 / ml, add 96-well culture plate, add 100 μ l in each hole, each kind of cell is divided into 3 groups respectively: test group (different concentration chemotherapeutic drug VCR), negative control group (do not add medicine), blank control group (do not add cell only add culture medium). Place the 96-well plate at 37°C, 5% CO 2 In a saturated humidity incubator, after culturing for 48 hours, add 5g / L MTT20μl to each well, and after continuing to cultivate for 4 hours, add 100μl / well of triplex solution, culture over the liquid, select a wavelength of 570nm, measure the OD value on a microplate reader, and calculate Cell survival rate, IC50 value of chemotherapeutic drugs, drug resistanc...

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PUM

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Abstract

The invention belongs to the field of pharmaceutical manufacture, and relates to the structural modification of tetrandrine and application of multidrug resistance of reversal tumor cells, in particular to a 5-substituted tetrandrine compound and the application thereof in preparing anticarcinogen sensitizer. The invention discloses the 5-substituted tetrandrine compound, a pharmaceutically acceptable salt thereof, a preparation method thereof, a medicine combination, and the application of the above in an anticarcinogen sensitizer. In the compound, R is a substituted aryl group, a 5-element or 6-element heterocyclic ring, a cyano group, an amino group, an azide group, a carboxylic group and ester. The 5-substituted tetrandrine compound and the pharmaceutically acceptable salt thereof have favorable reversing activity to the multidrug resistance of tumor cells and can be used for preparing the anticarcinogen sensitizer.

Description

technical field [0001] The invention belongs to the field of pharmacy, and relates to the structural modification of tetrandrine and its application in reversing the multidrug resistance of tumor cells, in particular to 5-substituted tetrandrine compounds and their application in the preparation of anticancer drug sensitizers . Background technique [0002] According to the estimates of the American Cancer Society, more than 90% of the approximately 490,000 deaths of cancer patients each year are related to drug resistance to varying degrees. The multidrug resistance of tumor cells makes it difficult for anti-tumor drugs to exert the expected effect. Tumor cells develop resistance to anticancer drugs, especially multidrug resistance (MDR), which refers to the resistance of tumor cells to a variety of anticancer drugs with different structures and mechanisms of action at the same time. Antineoplastic drugs of natural origin produce cross-resistance. Therefore, reversing the...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D491/18A61K31/4748A61K31/5377A61K31/496A61P35/00A61P35/02
Inventor 杨萍程捷恺吴利新
Owner FUDAN UNIV
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