Application of dehydrogenated silibinin diether in preparation of medicaments for preventing and treating leukemia

A technology of dehydrogenated water and thripin ether, which is used in drug combinations, medical preparations containing active ingredients, anti-tumor drugs, etc. Small, simple method, huge social and economic benefits

Inactive Publication Date: 2010-07-28
DALI UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0004] In recent years, researchers have discovered a variety of chemical reversal agents, such as verapamil (VRP), cyclosporin A (CsA), tamoxifen, etc., but most of these chemical reversal agents have a single target, and in vivo application can cause different effects. The degree of adverse reactions or poor reversal effects and other issues limit its clinical application

Method used

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  • Application of dehydrogenated silibinin diether in preparation of medicaments for preventing and treating leukemia

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] Example 1 : Preparation of 7,20-bis(1-butenyl)-dehydrosilibinin ether

[0023]

[0024] In a dry reaction flask, 0.241 g of silibinin was dissolved in 3 ml of DMF, 0.276 g of potassium carbonate was added, and stirred for 10 minutes to dissolve completely. 0.125 ml of 4-bromo-1-butene was slowly added dropwise, stirred for 10 minutes, and heated to reflux for 3 hours. Stand to cool, add 15 ml of distilled water, extract with ethyl acetate three times (20 ml each time), combine the organic layers, wash with 20 ml of distilled water, dry over anhydrous sodium sulfate, and concentrate under reduced pressure. The brownish-yellow crude product was obtained, and it was eluted with 200-300 mesh silica gel (20 g) with chloroform: ethyl acetate: acetic acid = 20:1:0.1 to obtain 68.8 mg of yellow crystals. Yield 23.7%.

[0025] 7,20-bis(1-butenyl)-dehydrosilibinin ether: 2-[2,3-dihydro-3-(4-enbutyloxy-3-methoxyphenyl) -2-Hydroxymethyl-1,4-benzodioxane-6-]-7-(enbutyloxy)-3,...

Embodiment 2

[0026] Example 2 : Inhibition of 7,20-bis(1-butenyl)-dehydrosilibinin on the proliferation of human chronic myelogenous leukemia cell line (K562) in vitro

[0027] 2.1 Cell culture:

[0028] Human chronic myelogenous leukemia (K562) cells were cultured with RPMI 1640 medium containing 10% calf serum, 100 U / ml penicillin and 100 U / ml streptomycin. cells in 5×10 per well 4 Seed into 96-well plates at 37 °C, 5% CO 2 Incubate for 24 hours in a humidified incubator.

[0029] 2.2 Determination of cell viability using the modified MTT method:

[0030] After the cells were incubated for 24 hours, the dimethyl sulfoxide solution of the newly prepared compound 7,20-bis(1-butenyl)-dehydrosilibinin ether was added to each well in a concentration gradient, so that The final concentrations of the compound in the wells were 100 μg / ml, 50 μg / ml, 25 μg / ml, 5 μg / ml, respectively. After 72 hours, add 10 μl of MTT (5 mg / ml) in saline solution, and continue to incubate at 37°C, 5% CO 2 Cul...

Embodiment 3

[0034] Example 3 : Inhibition of 7,20-bis(1-butenyl)-dehydrosilibinin on the proliferation of human chronic myelogenous leukemia cell line doxorubicin-resistant (K562 / ADR) in vitro

[0035] 3.1 Establishment of human chronic myelogenous leukemia doxorubicin-resistant strain (K562 / ADR) cell line

[0036] Human chronic myelogenous leukemia (K562) cells were cultured with RPMI 1640 medium, containing 5% calf serum in the medium, adding 0.1 mg / L doxorubicin, and then gradually increasing the concentration of doxorubicin every two weeks until The final concentration of doxorubicin was 1.0 mg / L. Start the experiment after observing the stability of the cells. cells in 5×10 per well 4 Seed into 96-well plates at 37 °C, 5% CO 2 Incubate for 24 hours in a humidified incubator.

[0037] 3.2 Use the modified MTT method to determine the growth inhibitory effect of positive drugs cisplatin and doxorubicin on K562 / ADR cells:

[0038] After the cells were incubated for 24 hours, the n...

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Abstract

The invention provides application of dehydrogenated silibinin diether in the preparation of medicaments for preventing and treating leukemia and relates to medical application of lignin flavone silibinin to the prevention and treatment of chronic myeloid leukemia. Particularly, the invention relates to application of dehydrogenated silibinin diether, of which the seventh bit and the twentieth bit are substituted by 1-butylene, or pharmaceutically acceptable salts thereof in the preparation of medicaments for preventing and treating chronic myeloid leukemia. Natural products of the silibinin are treated by simple steps to synthesize the compound. The pharmacological tests prove that the compound can potently inhibit the in-vitro proliferation of human chronic myeloid leukemia cell strains(K562) and adriamycin drug-resistant strains (K562 / ADR), and the IC50 values are 11.9+ / -1.6 micromoles and 15.9+ / -1.2 micromoles respectively.

Description

technical field [0001] The present invention relates to the fields of natural medicinal chemistry and pharmacology, in particular, the present invention relates to the use of dehydrosilibinin diether or its pharmaceutically acceptable salts substituted by 7-position and 20-position 1-butene in the preparation of anti-leukemia drugs , the present invention found that the compound has a strong inhibitory effect on the in vitro proliferation of human chronic myelogenous leukemia cell line (K562) and its doxorubicin-resistant strain (K562 / ADR), and can be expected to be used for the preparation of therapeutically relevant human chronic myelogenous leukemia cell line Use of myelogenous leukemia drugs. Background technique [0002] With the rapid development of society, the number of people suffering from tumor diseases is increasing. The annual incidence of tumors in my country has reached nearly 2 million cases, ranking among the forefront of morbidity and mortality. The situa...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/357A61P35/02A61P35/00
Inventor 巫秀美彭芳肖怀刘光明杨晓莉杨雷香赵昱
Owner DALI UNIV
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