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The New Application of Levocordate Derivatives

A compound and the technology of tumor neovascularization, applied in the field of application of levocordate derivatives in the field of neovascularization inhibitors, can solve the problems of no microcirculation function, disordered distribution mode, etc.

Active Publication Date: 2017-04-12
INST OF CHEM CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The neovascularization induced by tumor cells has defects in structure, disordered distribution, and lack of complete microcirculation function. It is quite different from the blood vessels of normal host tissues and belongs to immature blood vessels.

Method used

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  • The New Application of Levocordate Derivatives
  • The New Application of Levocordate Derivatives
  • The New Application of Levocordate Derivatives

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] Embodiment 1, the inhibitory experiment of levocordate derivatives on the proliferation of human umbilical vein endothelial cells (HUVEC)

[0029] 1. Materials:

[0030] Tetramethylazolazolium Blue (MTT): Dissolve MTT in 0.01M phosphate buffered saline (PBS) to a final concentration of 5 mg / ml, filter and sterilize, and store in the dark at 4°C after aliquoting.

[0031] Cell line: human umbilical vein endothelial cells (HUVEC) (purchased from Peking Union Medical College Cell Resource Center);

[0032] 2. The specific operation steps are as follows:

[0033] 1) Refer to relevant literature methods (Chinese Journal of Pharmacology and Toxicology, 2011, 25(6): 543-545; Acta Pharmaceutica Sinica, 2009, 44(12): 1359-1363; Mechanism study, Chinese Journal of Pharmaceutical Sciences of PLA, 2010,26(6):489-492), human umbilical vein endothelial cells in the logarithmic growth phase

[0034] (HUVEC) was made into cell suspension, and each well of a 96-well plate was inocula...

Embodiment 2

[0043] Example 2, MTT reduction method to detect the in vitro anticancer activity test of L-tetrahydropalmatine derivatives

[0044] The basic principle of the MTT method is: Tetrazolium [MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide] is a dye that can accept hydrogen atoms. The dehydrogenase associated with nicotinamide adenine dinucleotide phosphate (NADP, nicotinamide adenine dinucleotide phosphate) in the mitochondria of living cells can convert yellow MTT into insoluble blue-purple formazan in cells, while dead cells have no this function. After dissolving formazan with dimethyl sulfoxide (DMSO, Dimethyl sulfoxide), the optical density value is measured with a microplate reader at a certain wavelength, and the survival rate of the cells can be quantitatively measured.

[0045] 1. Materials:

[0046] Tetrazolium salt (MTT): Dissolve MTT in 0.01M phosphate buffered saline (PBS) to a final concentration of 5 mg / ml, filter and sterilize, and store in th...

Embodiment 3

[0060] Embodiment 3, the chicken embryo chorioallantoic membrane method (CAM) measures the inhibitory experiment of levocordate derivatives (III, IV or V) to neovascularization

[0061] Chicken chorioallantoic membrane (chick embryo chorioallantoic membrane, CAM) is formed in the early embryo, at this time, the immune system of the chick embryo body has not been fully established, and there is almost no rejection reaction to various foreign bodies. The drug carrier is placed on its surface, The effect of drugs on angiogenesis can be observed. The chicken embryo model is sensitive to anti-angiogenic drugs and is currently used in drug screening [Ribatti D.The chick embryo chorioallantoic membrane in the study of tumor angiogenesis[J].Rom J Morphol Embryol,2008, 49(2):131-135; Ribatti D. The chick embryo chorioallantoic membrane as an in vivo assay to study antiangiogenesis [J]. Pharmaceuti cals, 2010, 3(3): 482-513.].

[0062] The specific operation of the experiment is as foll...

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Abstract

The invention discloses a new use of L-tetrahydropalmatine derivatives. The new use refers to the use of the L-tetrahydropalmatine derivatives expressed by a formula II as shown in the description or pharmaceutically acceptable salts thereof in preparing tumor angiogenesis inhibitors. The results of in vitro anticancer activity tests indicate that the L-tetrahydropalmatine derivatives have a good inhibition effect on the proliferation of human non-small cell lung cancer A549, human umbilical vein endothelial cells (HUVEC) and angiogenesis. The results also indicate that the L-tetrahydropalmatine derivatives expressed by the formula II or pharmaceutically acceptable salts thereof can be applied to preparing the tumor angiogenesis inhibitors and the medical application of the L-tetrahydropalmatine derivatives is expanded.

Description

technical field [0001] The present invention relates to the new use of levocordantine derivatives, in particular to the application of levocordantine derivatives in angiogenesis inhibitors. Background technique [0002] Malignant tumor is one of the major diseases that endanger human health and life. In my country, according to the statistics of the Ministry of Health, the total number of new tumor patients is about 2.127 million each year, of which there are about 1.06 million new patients with malignant tumors. Although important progress has been made in the development and application of anticancer drugs for more than half a century, chemotherapy for certain types of tumors has achieved outstanding curative effects. However, the effect of most types of drug treatment is still unsatisfactory. Therefore, the discovery and development of new anti-tumor drugs is still an important topic and task in the field of biomedical science. [0003] Studies in recent years have sho...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/4375A61P35/00A61P35/04C07D455/03
CPCA61K31/4375C07D455/03
Inventor 张虹沈刚王立霞唐亚林
Owner INST OF CHEM CHINESE ACAD OF SCI
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