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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 anti-tumor activity and high neurotoxicity and side effects of the existing alkaloids of the genus Vinca

Method used

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  • Cathearanthus alkaloid
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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0024] Obtaining of Compound A1

[0025] 6'-N oxidation-epoxy vinblastine (6'-N b -oxide-leurosine) at the 3-position for semi-synthetic modification, the original -COOCH at the 3-position 3 Replace with -COOCH 2 C 6 h 5 , whose structure is:

[0026]

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

[0028] IC 50 Value (μM / L)

[0029] cancer cell line

Compound A1

Vinblastine

He La

7.3

16

A549

2.9

3.6

DLD-1

10.7

14

MX-1

1.6

1.8

OVCAR-3

1.5

2.0

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

[0031]

[0032] Activity experiments showed that the semi-lethal dose (IC 50 ) values ​​are all less than vinblastine, indicating that it has better antitumor activity than vinblastine; meanwhile, the mouse animal experiment results show that the number of mice with abnormal conditions is significantly lowe...

Embodiment 2

[0034] Obtaining of compound B1

[0035] 6'-N oxidation-epoxy vinblastine (6'-N b -oxide-leurosine) at the 3-position for semi-synthetic modification, the original -COOCH at the 3-position 3 Replace with -COOCH 2 C 6 h 5 , while the original -OCOCH at the 4-position 3 Substituted by -OH, its structure is:

[0036]

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

[0038] IC 50 Value (μM / L)

[0039] cancer cell line

Compound B1

Vinblastine

He La

8.3

16

A549

3.0

3.6

DLD-1

11.6

14

MX-1

1.6

1.8

OVCAR-3

1.8

2.0

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

[0041]

[0042] Activity experiments showed that the semi-lethal dose (IC 50 ) values ​​are all less than vinblastine, indicating that it has better anti-tumor activity than vinblastine; meanwhile, the mouse animal experiment results show that t...

Embodiment 3

[0044] Obtaining of compound A2

[0045] 6'-N oxidation-epoxy vinblastine (6'-N b -oxide-leurosine) at the 3-position for semi-synthetic modification, the original -COOCH at the 3-position 3 Replaced with -COOC 6 h 5 , whose structure is:

[0046]

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

[0048] IC 50 Value (μM / L)

[0049] cancer cell line

Compound A2

Vinblastine

He La

14.6

16

A549

3.5

3.6

DLD-1

12.8

14

MX-1

1.8

1.8

OVCAR-3

1.8

2.0

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

[0051]

[0052]

[0053] Activity experiments showed that the semi-lethal dose (IC 50 ) and slightly vinblastine, indicating that its anti-tumor activity is equivalent to that of vinblastine; meanwhile, the mouse animal experiment results show that the amount of abnormal situation mice is not significantly d...

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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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