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Application of 4-hydroxyl salicylanilide in preparation of anti-tumor drugs

A technology of hydroxysalicylanilide and medicine is applied in the application field of 4-hydroxysalicylanilide and the preparation of antitumor drugs, and can solve the problems of limited application of medicines and high proportion of recurrence or drug resistance of lymphoma patients

Active Publication Date: 2016-06-15
施菊妹
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But at the same time, there are still the following deficiencies: first, the effective rate of the above drugs in relapsed / refractory patients is only 25% to 50%; second, although the disease-free survival time is prolonged, most patients will eventually relapse, and Significant drug resistance occurs; third, some serious side effects such as neuritis limit the application of drugs
However, the proportion of lymphoma patients who develop relapse or drug resistance remains high

Method used

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  • Application of 4-hydroxyl salicylanilide in preparation of anti-tumor drugs
  • Application of 4-hydroxyl salicylanilide in preparation of anti-tumor drugs
  • Application of 4-hydroxyl salicylanilide in preparation of anti-tumor drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0023] Example 1: Killing activity against human multiple myeloma cells

[0024] 1. Experimental materials:

[0025] (1) Cell line: human multiple myeloma cells (H929 cells, OPM2 cells, U266 cells, OCI-MY5 cells, RPMI8266 cells) (ATCC, USA, preserved in our laboratory), cultured in 1640 medium (containing 10% fetal bovine serum).

[0026] (2) Main reagents: 1640 medium (Gibco, USA), fetal bovine serum (Gibco, USA), 4-hydroxy salicylanilide (Shanghai Titan Chemical Co., Ltd.), CellCountingKit-8 kit (CCK8, Japan Co., Ltd. Tongren Institute of Chemistry).

[0027] (3) Main instruments: carbon dioxide incubator (ThermoForma, USA), automatic microplate reader (Bio-TEK, Elx800).

[0028] 2. Experimental method:

[0029] (1) Cell culture

[0030] The cells were cultured in 1640 medium (containing 10% fetal bovine serum, pH 7.2), the medium was added with 2mmol / L glutamine, and placed in a cell culture incubator at 37°C and 5% CO2.

[0031] (2) CCK8 kit to measure the cytotoxici...

Embodiment 2

[0036] Embodiment 2: Animal experiment for multiple myeloma

[0037] 1. Experimental materials

[0038] (1) Cell line: human multiple myeloma cells (H929 cells) (US ATCC, preserved in our laboratory), cultured in 1640 medium (containing 10% fetal bovine serum).

[0039] (2) Experimental animals: male BALB / C nude mice (6-8 weeks, purchased from Shanghai Xipuer-Bikay Experimental Animal Co., Ltd.), placed in an SPF-grade environment (animal room of the Central Laboratory of Shanghai Tenth People's Hospital) ).

[0040] 2. Experimental method

[0041] (1) Cell culture See Example 1.

[0042] (2) Animal experiments

[0043] Will contain 2 x 10 6 The 1640 medium of H929 cells was injected subcutaneously into the right armpit of nude mice, and when the tumors grew and could be measured, they were randomly divided into the control group and the treatment group. The nude mice in the treatment group were injected with 100 mg / kg of 4-hydroxysalicylanilide through the tail vein eve...

Embodiment 3

[0047] Example 3: Killing activity against human lymphoma cells

[0048] 1. Experimental materials

[0049] Human lymphoma cells (SUDHL-4 cells, OCI-LY1 cells, OCI-LY8 cells, DB cells, NU-DUL-1 cells, U2932 cells, TMD8 cells) (US ATCC, preserved in our laboratory). IMDM medium (Gibco, USA). DMEM medium (low sugar) (Gibco, USA). Others are the same as embodiment 1.

[0050] 2. Experimental method

[0051] OCI-LY8 cells were cultured in IMDM medium. U2932 cells were cultured in DMEM medium (low glucose). Others are the same as embodiment 1.

[0052] 3. Experimental results

[0053] For experimental data, see Figure 8-Figure 14 .

[0054] Conclusion: 4-hydroxysalicylanilide has killing activity on human lymphoma cells, the IC50 of SUDHL-4 cells, OCI-LY1 cells, OCI-LY8 cells, DB cells, NU-DUL-1 cells, U2932 cells and TMD8 cells They are 73 μM, 117 μM, 76 μM, 178 μM, 188 μM, 156 μM and 164 μM, respectively.

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PUM

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Abstract

The invention relates to novel application of 4-hydroxyl salicylanilide in the pharmaceutical field, and the 4-hydroxyl salicylanilide can be used for preparing drugs for preventing and treating multiple myeloma and lymphoma.The 4-hydroxyl salicylanilide has the advantages that in vitro, the compound can effectively inhibit cell growth of the multiple myeloma and the lymphoma; in vivo, the compound can effectively inhibit growth of the multiple myeloma and the lymphoma of a mouse and can be developed into the preventing and treating drugs for the multiple myeloma and the lymphoma.The 4-hydroxyl salicylanilide is an old drug for protecting the liver and is high in safety, and it is indicated that the 4-hydroxyl salicylanilide has the very good medicinal prospect in the cancer field.

Description

technical field [0001] The invention relates to the technical field of antitumor drugs, in particular to the application of 4-hydroxy salicylanilide in the preparation of antitumor drugs. Background technique [0002] Multiple myeloma (MM) is a malignant disease of abnormal proliferation of clonal plasma cells. It is the second most common malignant tumor in the hematological system, accounting for about 10% of hematological malignancies. Still incurable, the median survival time is 5 to 6 years. The main methods of traditional treatment of multiple myeloma are chemotherapy and hematopoietic stem cell transplantation, and its clinical efficacy is difficult to maintain. In the past 10 years, with the emergence of new drugs such as the proteasome inhibitor bortezomib and the immunomodulators thalidomide and lenalidomide, the complete remission rate and overall survival rate of multiple myeloma patients have increased significantly. But at the same time, there are still the f...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/609A61P35/00
CPCA61K31/609A61K9/0019A61K9/48A61P35/00
Inventor 施菊妹朱维良邵吉民杨洸徐志建刘霞高露李波陈新焕
Owner 施菊妹
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