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A kind of basic acid derivative with the function of preventing and treating tumor metastasis

A technology for anticancer drugs and tumor metastasis, which can be applied in the fields of antineoplastic drugs, medical preparations containing active ingredients, organic chemistry, etc., and can solve the problem of preparing drugs for the prevention and treatment of tumor metastasis from derivatives of anticancer drugs that have not been found. However, there are no reports in the literature on the prevention and treatment of tumor metastasis by the derivatives of basic acid, which can inhibit the ability of movement and migration, improve solubility and good selectivity.

Active Publication Date: 2019-03-05
JILIN ACAD OF TRADITIONAL CHINESE MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] Before the completion of the present invention, except for the research of the inventor, there was no literature report that the derivatives of basic acid had the effect of preventing and treating tumor metastasis, nor had it been found that the derivatives of basic acid were used in the preparation of prevention and treatment of tumor metastasis. reports on drug use

Method used

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  • A kind of basic acid derivative with the function of preventing and treating tumor metastasis
  • A kind of basic acid derivative with the function of preventing and treating tumor metastasis
  • A kind of basic acid derivative with the function of preventing and treating tumor metastasis

Examples

Experimental program
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Effect test

Embodiment 1

[0033] Example 1 Study on Inhibitory Proliferation of Hepatic Cancer Cell HepG2 and LO2 Toxicity of Hepatic Acid and Its Derivatives to Normal Liver Cells

[0034] After digesting hepatoma cells HepG2 in the logarithmic growth phase and human normal liver cells LO2, the cell density was adjusted to 1×10 5 cells / mL, seeded in a 96-well plate, 100 μL per well, placed at 37°C, 5% CO 2 Cultivate in the incubator for 24 hours; remove the old medium, add the test drug (basic acid and its derivatives) to dilute the stock solution of the test drug with the medium, set different concentrations, 100 μL per well, and set a blank For the control group, 5 replicate wells were set up for each group. After 24 hours of drug action, discard the drug-containing medium, add 100 μL of serum-free phenol red-free medium to each well, and then add 100 μL of 0.5 mg / mL MTT solution, and continue to incubate for 4 hours before terminating the culture; aspirate and discard the 96-well plate For the su...

Embodiment 2

[0038] Example 2 Bispinic acid and its derivatives inhibit the adhesion of liver cancer cell HepG2 to extracellular matrix

[0039] The fibronectin FN (fibronectin) stored at -20°C was placed in a 37°C water bath until it was completely melted, and then prepared into a FN working solution with a concentration of 10 μg / ml in serum-free culture medium. Use 100 μL / well FN working solution to completely cover the 96-well plate, leave it at room temperature overnight, and gently suck off the liquid. Take HepG2 cells in the logarithmic growth phase and make a single cell suspension with a cell concentration of 5×10 5 / ml, mixed with different concentrations of drugs (0, 0.25, 0.5, 1.0, 2.5, 5.0 μM), and inoculated in FN-coated 96-well plates. After incubating at 37°C and 5% CO2 for 2 hours, lightly wash with PBS for 3 times, add 10 μl of MTT culture solution after drying, continue to incubate for 4 hours, discard the supernatant, add 100 μl DMSO, and use an enzyme-linked detector t...

Embodiment 3

[0044] Example 3 Experiment of Inhibiting the Adhesion of Hepatic Cancer Cells HepG2 and HUVEC Cells by Respiratory Acid and Its Derivatives

[0045] Human umbilical vein endothelial cells were isolated from umbilical cord veins delivered in normal pregnancy and cultured. Digest the HUVEC cells in the logarithmic phase and inoculate them in a 24-well plate. When the endothelial cells in the 24-well plate are full of the plate, wash it two or three times with PBS, and then add the endothelial stimulating factor IL-1β at a concentration of 1 ng / L culture medium, incubated at 37°C, 5% CO2 for 4h. After 4 hours, take out the well plate, wash it two or three times with PBS, take HepG2 cells in the logarithmic growth phase, and make 4×10 cells after fluorescent labeling. 5 / ml -1 Single cell suspension, and RPM-1640 culture solution with different concentrations of derivatives of the present invention were added, the final drug concentrations were: 0, 0.25, 0.2, 1.0, 2.5, 5.0 μM,...

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Abstract

The invention provides application of a rotundic acid derivant in preparation of a medicine for preventing and treating tumour metastasis. An in vitro experiment proves that the rotundic acid derivant disclosed by the invention has significant inhibition effects on proliferation, adhesion, migration and the like of tumor cells, and is safe and low-toxicity to normal cells of a human body. An in vivo animal experiment proves that experimental lung metastasis of B16-F10 melanoma of mice can be effectively reduced, and a preferable tumour metastasis prevention effect is prompted. The rotundic acid derivant disclosed by the invention can be applied to a medicine for preventing the tumour metastasis, so that new application of the rotundic acid derivant to prevention and treatment of tumors is developed, and a new choice is provided for developing a new drug for treating the tumour metastasis and preventing postoperative re-metastasis of malignant tumour; moreover, the rotundic acid derivant has more obvious pharmacological activity.

Description

technical field [0001] The invention relates to a medicine for preventing postoperative metastasis of malignant tumors, in particular to the application of abic acid derivatives in medicines for preventing and treating tumor metastasis, and belongs to the field of medicine. Background technique [0002] Malignant tumors are one of the major diseases that seriously endanger human health. Most of the deaths of cancer patients are caused by late metastasis of malignant tumors. Tumor metastasis refers to the process that tumor cells dissociate from the primary tumor, infiltrate into the surrounding tissue, invade into the circulatory system, and then metastasize in vivo, and adhere to and infiltrate with endothelial cells to form metastases. Tumor metastasis is one of the main reasons for tumor refractory and recurrence, and also a key factor leading to the death of tumor patients. Clinical diagnosis results show that more than 60% of newly diagnosed tumor patients have metasta...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07J63/00A61K31/58A61P35/04
CPCC07J63/008
Inventor 南敏伦赫玉芳王雪赵昱玮何忠梅赵全成
Owner JILIN ACAD OF TRADITIONAL CHINESE MEDICINE