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Podophyllotoxin derivatives as well as synthetic method and application thereof

A technology of podophyllotoxin and derivatives, applied in the field of preparation and its application in tumor suppression, which can solve the problems of poor water solubility and narrow anticancer spectrum

Inactive Publication Date: 2015-09-09
NANJING UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

VP-16 and VM-26 have the disadvantages of narrow anti-cancer spectrum and poor water solubility, and also have some side effects

Method used

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  • Podophyllotoxin derivatives as well as synthetic method and application thereof
  • Podophyllotoxin derivatives as well as synthetic method and application thereof
  • Podophyllotoxin derivatives as well as synthetic method and application thereof

Examples

Experimental program
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Effect test

example 1

[0016] Example 1: Preparation of podophyllotoxin derivatives

[0017] At room temperature, add podophyllotoxin, corresponding carboxylic acid, refined dichloromethane and catalyst to a 50mL round-bottomed flask in sequence. TLC detects that the reaction is complete, and the corresponding podophyllotoxin derivatives are obtained by column chromatography. The physicochemical data of the corresponding compounds are as follows:

[0018] Compound 1: Yield: 77.3%, Mp: 116~118℃. 1 H NMR (300MHz, CDCl 3 )δ7.88-7.69 (m, 4H), 7.29-7.11 (m, 5H), 6.82-6.69 (m, 1H), 6.54 (d, J=8.2Hz, 1H), 6.42-6.25 (m, 2H) , 5.99(d, J=5.8Hz, 2H), 5.93(s, 1H), 5.31(dd, J=8.9, 4.8Hz, 1H), 4.61(s, 1H), 4.59-4.48(m, 1H), 4.27(d, J=7.8Hz, 1H), 3.88-3.67(m, 9H), 3.56-3.39(m, 2H), 2.97-2.92(m, 1H), 2.19(s, 1H).

[0019] Compound 2: Yield: 73.8%, Mp: 119~121℃. 1 H NMR (300MHz, CDCl 3 )δ7.82-7.67 (m, 4H), 7.25-7.06 (m, 5H), 6.78-6.66 (m, 1H), 6.49 (d, J=8.9Hz, 1H), 6.39-6.21 (m, 2H) , 5.95(d, J=5.7Hz, 2H), 5...

example 2

[0036] Example 2: Application of Formula I Class Podophyllotoxin Derivatives

[0037] We studied the anti-tumor activity of podophyllotoxin derivatives of formula I, selected tumor cells MCF-7, A549, and Hela as detection cells, and used MTT colorimetry as the detection method, and measured their absorbance at 570nm with a microplate reader And calculate the OD value.

[0038] IC 50 The value calculation method is as shown in the formula:

[0039] Cell inhibition rate (%)=(OD value of control group-OD value of experimental group) / OD value of control group×100%

[0040] The results show that podophyllotoxin derivatives have certain potential in anti-tumor. The corresponding results are attached figure 1 , 2 , 3.

[0041] The results of cell activity showed that the activity of compound 9 was significantly better than other derivatives, and the IC of MCF-7, A549 and Hela cell lines were respectively 50 The values ​​were 0.88 μM, 7.82 μM, and 1.21 μM.

example 4

[0042] Example 4: Compound 9 blocks cell cycle in G2 / M phase

[0043]MCF-7 cells were treated with compounds at different concentrations (0, 1, 2, 4 μM) for 24 hours, and the cells were collected for detection by flow cytometry. The results are shown in the appendix Figure 4 .

[0044] The podophyllotoxin derivatives of the present invention can be prepared into antitumor drugs.

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Abstract

The invention belongs to the technical field of chemical pharmacy, and particularly relates to podophyllotoxin derivatives and application of the podophyllotoxin derivatives in aspect of tumor suppression. Corresponding compound is obtained through a synthesis technology, and activity studies on antitumor in vitro show that the podophyllotoxin derivatives have strong inhibitory activity to tumor cell strains.

Description

1: Technical field [0001] The invention belongs to the technical field of chemical pharmacy, and specifically relates to the preparation of a class of podophyllotoxin derivatives and their application in tumor suppression. Two: background technology [0002] Podophyllotoxin (Podophyllotoxin) is a class of natural products with significant anti-tumor activity. It is a class of lignan structure compounds with a core of 2,3-butylpropyl-4-aryl tetrahydronaphthalene. Podophyllotoxin, a natural product, has significant antitumor and antiviral activities, but due to its high toxicity and side effects, its application has been greatly restricted. [0003] In the 1940s, King and Shllivan first reported that podophyllotoxin has the effect of colchicine, and further confirmed that podophyllotoxin has strong anticancer activity. In the early 1950s, foreign countries began to modify the structure of podophyllotoxin, synthesized and screened a large number of derivatives, and found etopo...

Claims

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Application Information

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IPC IPC(8): C07D493/04C07D519/00A61P35/00
CPCC07D493/04C07D519/00
Inventor 王小明杨永华王子振邱寒月罗越琳
Owner NANJING UNIV
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