Cathearanthus alkaloid

A technology of periwinkle and alkaloids, which can be applied in drug combinations, compounds of group 5/15 elements of the periodic table, organic chemistry, etc., can solve the problems of high neurotoxic side effects and low anti-tumor activity, and achieve good anti-tumor activity , low neurotoxicity

Inactive Publication Date: 2010-01-20
HUAZHONG UNIV OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The invention provides a class of alkaloids of the genus Vinca, which solves the problems of low

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Example Embodiment

[0023] Example 1

[0024] Obtaining compound A1

[0025] The 6’-N oxidation-epoxyvinblastine (6’-N b -oxide-leurosine) at position 3 is semi-synthetically modified, and the original -COOCH at position 3 3 Replaced with -COOCH 2 C 6 H 5 , Its structure is:

[0026]

[0027] Half lethal dose (IC 50 ) Experimental results:

[0028] IC 50 Value (μM / L)

[0029] Cancer cell line

[0030] Mouse animal experiment results (the number of abnormal mice):

[0031]

[0032] Activity experiments show that compound A1 has a semi-lethal dose (IC 50 ) Values ​​are less than vinblastine, indicating that it has better anti-tumor activity than vinblastine; at the same time, the results of mouse animal experiments show that the number of abnormalities in mice with compound A1 is significantly lower than that of vinblastine. (P<0.01), indicating that the neurotoxicity of the compound is significantly less than vinblastine.

Example Embodiment

[0033] Example 2

[0034] Obtaining compound B1

[0035] The 6’-N oxidation-epoxyvinblastine (6’-N b -oxide-leurosine) at position 3 is semi-synthetically modified, and the original -COOCH at position 3 3 Replaced with -COOCH 2 C 6 H 5 , And the original -OCOCH at 4 positions 3 Replaced by -OH, its structure is:

[0036]

[0037] Half lethal dose (IC 50 ) Experimental results:

[0038] IC 50 Value (μM / L)

[0039] Cancer cell line

[0040] Mouse animal experiment results (the number of abnormal mice):

[0041]

[0042] Activity experiments show that compound B1 has a semi-lethal dose (IC 50 ) Values ​​are less than vinblastine, indicating that it has better anti-tumor activity than vinblastine; at the same time, the results of mouse animal experiments show that the number of abnormalities in mice with compound B1 is significantly lower than that of vinblastine. (P<0.05), indicating that the neurotoxicity of the compound is significantly less than vinblastine.

Example Embodiment

[0043] Example 3

[0044] Obtaining compound A2

[0045] The 6’-N oxidation-epoxyvinblastine (6’-N b -oxide-leurosine) at position 3 is semi-synthetically modified, and the original -COOCH at position 3 3 Replaced by -COOC 6 H 5 , Its structure is:

[0046]

[0047] Half lethal dose (IC 50 ) Experimental results:

[0048] IC 50 Value (μM / L)

[0049] Cancer cell line

[0050] Mouse animal experiment results (the number of abnormal mice):

[0051]

[0052]

[0053] Activity experiments show that compound A2 has a semi-lethal dose (IC 50 ) And slightly vinblastine, indicating that its anti-tumor activity is equivalent to vinblastine; at the same time, the results of animal experiments in mice show that the number of mice with compound A2 is not significantly different from that of vinblastine. It shows that the neurotoxicity of this compound is equivalent to vinblastine.

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Abstract

The invention relates to a cathearanthus alkaloid, belonging to medical alkaloid and derivative thereof. The cathearanthus alkaloid is obtained by structural modification of 6'-N oxidation-epoxy catharanthine, and solves the problems of low antitumor activity and high toxic side effect on nerves of the existing cathearanthus alkaloid. The cathearanthus alkaloid is obtained by semi-synthetic modification of the third site of the 6'-N oxidation- epoxy catharanthine; besides, the fourth site of the 6'-N oxidation- epoxy catharanthine can be further semi-synthetically modified for preparing antitumor medicines. Proven by a median lethal dose (IC50) experiment of cancer cell lines and an animal experiment of mice, the compounds of the invention have favorable antitumor activity and low nerve toxicity, and is of great significance to the development of new antitumor medicines.

Description

technical field [0001] The invention belongs to alkaloids and derivatives thereof with medicinal value, and specifically relates to a class of vinca alkaloids obtained by structurally modifying 6'-N oxidation-epoxy vinblastine. Background technique [0002] In the 21st century, malignant tumors are still serious diseases that endanger human life and health. In 2000, there were 10.1 million new cancer cases worldwide, 6.2 million deaths, and 22.4 million cancer patients. Due to the aging of the population and the existence of problems such as smoking and infection in my country, in the early 1990s, the annual number of cancer deaths reached 1.3 million, and in recent years there is an upward trend. Therefore, the research and development of anticancer drugs It has always been a hot spot of common concern of the government, enterprises and research and development personnel. Antineoplastic drugs derived from plants are still the protagonists in the antineoplastic drug market....

Claims

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Application Information

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IPC IPC(8): C07D519/04C07F9/6561A61K31/475A61K31/675A61P35/00
Inventor 余龙江李硕赵春芳向福
Owner HUAZHONG UNIV OF SCI & TECH
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