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Parthenolide dithiocarbamate derivative, salt and medicinal composition thereof, and use of derivative, salt or medicinal composition

A technology of ester dithiocarbamate and derivatives is applied in the application field of preparing anti-cancer or auxiliary anti-cancer drugs, and can solve the problems of water solubility, poor plasma stability, low activity and the like

Active Publication Date: 2019-04-19
NANKAI UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, its water solubility and plasma stability are poor, and its activity is also low. It is expected to further improve its activity, water solubility and plasma stability by modifying its structure.

Method used

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  • Parthenolide dithiocarbamate derivative, salt and medicinal composition thereof, and use of derivative, salt or medicinal composition
  • Parthenolide dithiocarbamate derivative, salt and medicinal composition thereof, and use of derivative, salt or medicinal composition
  • Parthenolide dithiocarbamate derivative, salt and medicinal composition thereof, and use of derivative, salt or medicinal composition

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0014] Example 1: Synthesis of compound 1-16

[0015] The nucleophilic addition reaction of various amines with carbon disulfide under the action of triethylamine produces various dithiocarbamates, and then performs Michael addition with the α, β-unsaturated double bond of parthenolide Reaction, one-pot method to prepare 1-13. After the aminopyridine is reacted with butyl lithium, it undergoes nucleophilic addition reaction with carbon disulfide to prepare dithioformate, and then undergoes Michael addition reaction with parthenolide to obtain compound 14 or 15.

[0016] Synthesis of compound 1

[0017] Place the reaction vial in an ice-water bath, add the solvents dichloromethane (2mL) and methanol (0.5mL), carbon disulfide (0.1mL, 1.5mmol) and triethylamine (0.15mL, 1.1mmol) in sequence, start stirring, Add methylamine hydrochloride (81mg, 1.2mmol) to the mixed solution, keep it for half an hour, then add parthenolide (248mg, 1.0mmol), raise it to room temperature, keep it for 8 h...

Embodiment 2

[0048] Example 2: Pharmacological effects of parthenolide dithiocarbamate derivatives or their salts

[0049] Match various cancer cells into 2×10 5 / mL cell suspension, add it to the 96-well round-bottom cell culture plate, add parthenolide dithiocarbamate derivatives or their salts, 3 wells for each test concentration, set at 37℃, 5% CO 2 After culturing for 72 hours under saturated humidity conditions, the absorbance (A) value was measured by the MTT method at 570nm wavelength of the enzyme-linked detector, and the inhibitory effect of the compound of the present invention on the tested cancer cells was calculated and repeated three times.

[0050] Table 1 Inhibitory activity of parthenolide dithiocarbamate derivatives on various cancer cells (IC 50 , ΜM)

[0051] Compound

KG1a

HL60

Doxorubicin (positive control)

0.75±0.05

0.022±0.005

Parthenolide

6.1±1.8

3.8±1.2

1

8.6±1.1

13.4±2.0

2

4.8±3.2

7.3±1.1

3

16.0±1.1

6.5±2.5

4

50.0±14.0

20.7±4.6

5

13.5±1.0

10.6±2.1...

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PUM

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Abstract

The invention provides a parthenolide dithiocarbamate derivative represented by formula (I), a salt and a medicinal composition thereof, and a use of the derivative, the salt or the medicinal composition, and concretely relates to a use of the parthenolide dithiocarbamate derivative and the salt thereof in the preparation of medicines for treating cancers and assistant medicines for treating cancers.

Description

Technical field [0001] The present invention relates to a pharmaceutical composition of parthenolide dithiocarbamate derivatives and salts thereof for the treatment of cancer or auxiliary treatment of cancer, and the pharmaceutical compounds and compositions are used in the preparation of anti-cancer or auxiliary anti-cancer compositions. The application in cancer drugs belongs to the field of pharmacy. Background technique [0002] Cancer stem cells, also known as tumor-initiating cells, refer to cancer cells with stem cell properties. Cancer stem cells can initiate tumors and drive tumor proliferation, can achieve unlimited proliferation of cancer cells through self-renewal, and can generate more mature ordinary cancer cells through differentiation [T.Reya,,SJMorrison,,MFClarke,and ILWeissman,,Nature .2001,414,105–111.]. Since cancer stem cells play an important role in tumor occurrence, metastasis and drug resistance [JEVisvader, GJ Lindeman, Cell Stem Cell 2012,10,717-728],...

Claims

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Application Information

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IPC IPC(8): C07D493/04C07C55/07A61K31/365A61K31/4025A61K31/4525A61K31/496A61K31/4402A61K31/4406A61P35/02
CPCC07D493/04
Inventor 张泉陈悦丁亚辉杨忠金戈伟智邝蓓佳
Owner NANKAI UNIV
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