Application of compound 6-O-angeloylplenolin to pharmacy

A technology of natural compounds and compositions, applied in the direction of active ingredients of boron compounds, active ingredients of heavy metal compounds, drug combinations, etc., can solve problems such as unclear synergistic effects, achieve good killing effect, high recurrence rate, and large toxic and side effects

Inactive Publication Date: 2011-10-05
KUNMING INST OF BOTANY - CHINESE ACAD OF SCI +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, there is no report on the novel mechanism of 6-OAP anticancer mechanism, and the role of this compound in

Method used

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  • Application of compound 6-O-angeloylplenolin to pharmacy
  • Application of compound 6-O-angeloylplenolin to pharmacy
  • Application of compound 6-O-angeloylplenolin to pharmacy

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0041] With different concentrations of natural compound 6-OAP (2 × 10 -6 -5×10 -6 M) Treat RPMI8226 cells, add 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfonic acid benzene after 44 hours )-2H-tetrazolium monosodium salt (WST-8) CCK-8 detection reagent, incubated for another 4 hours, and then measured its absorbance at 450 nm (OD450) with a microplate reader. It was found that 6-OAP treatment can significantly reduce the OD450 of RPMI8226 cells, and 6-OAP can significantly inhibit the proliferation of RPMI8226 cells, and the inhibition rate is positively correlated with the drug concentration (see figure 1 A). According to the growth inhibitory effect of 6-OAP on RPMI8226 cells, the half inhibitory concentration (IC) of 6-OAP on RPMI8226 cells was calculated 50 ) for 3.5 x 10 -6 M.

Embodiment 2

[0043] Use 7.5×10 -6 6-OAP of M treated U266 cells, detected the spindle checkpoint protein BubR1 by immunofluorescence after 24 hours, and found that 6-OAP promoted the aggregation of BubR1, indicating that the spindle checkpoint was activated ( figure 2 A). Furthermore, the Cdc20 bound to the spindle checkpoint protein Mad2 was detected by co-immunoprecipitation method, and it was found that the activation of the spindle checkpoint by 6-OAP can promote the binding of Cdc20 ( figure 2 B), Cdc20 is the binding activator of APC ubiquitin ligase, which will make APC lose its ubiquitination activity after being bound by spindle checkpoint protein. Therefore, with 7.5×10 -6 U266 and MM1S cells were treated with 6-OAP of M, and the ubiquitination activity of cyclin B1 was detected by immunoprecipitation after 24 hours, and it was found that the ubiquitination of cyclin B1 in 6-OAP-treated cells was reduced ( figure 2 C), showing that cyclin B1 degradation is inhibited. Wit...

Embodiment 3

[0045] After MM.1S cells were pre-attached for 24 hours, different concentrations (5×10 -6 -7.5×10 -6 M) MM.1S cells were treated with 6-OAP combined with doxorubicin, dexamethasone, and bortezomib. After 44 hours, MTT detection reagent was added to incubate for another 4 hours, and then the absorbance value at 570 nm was measured with a microplate reader (OD570). It was found that 6-OAP combined with doxorubicin ( image 3 A), dexamethasone ( image 3 B) and bortezomib ( image 3 C) Treatment can significantly reduce the OD570 of MM.1S cells, and 6-OAP combined with conventional drugs has a better effect on the treatment of MM.

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Abstract

The invention discloses a natural compound 6-O-angeloylplenolin (6-OAP) and application of medicinal composition thereof to the preparation of medicaments for treating multiple myeloma (MM) and lung cancer. The 6-O-angeloylplenolin and the medicinal composition thereof can activate a check point of a cell spindle, induce retardation and apoptosis of a mitotic phase, have obvious cytotoxicity in multiple myeloma and lung cancer cells and have effective anti-tumor proliferation effect in a nude mouse myeloma transplantation model. As a natural compound, the 6-OAP has the advantage of promoting cytotoxicity in the multiple myeloma and lung cancer cells by cooperating with routine medicaments, such as adriamycin, dexamethasone, bortezomib and the like. The 6-OAP shows ideal pharmacokinetic characteristics in an SD mouse and reaches a new level in the aspect of tumor target of natural compounds. The 6-OAP can provide a new treatment medicament to patients with MM and medicament resistant tumors and has the advantages of moderate dose and cost, convenience in administration, obvious treatment effect, low toxic and side effects and the like.

Description

technical field [0001] The invention belongs to the field of pharmaceutical technology, in particular to natural compound 6- O -Application of angeloylplenolin (6-OAP) and its pharmaceutical composition in the preparation of drugs for the treatment of cancer, especially in the preparation of drugs for the treatment of multiple myeloma, drug-resistant cancer and recurrent cancer, including lung cancer. Background technique [0002] Cancer is a leading cause of death worldwide, accounting for 7.6 million cancer deaths in 2008 (approximately 13% of all deaths). At present, lung cancer is the most common cancer in the world, accounting for 16% of all malignant tumors. The mortality rate of lung cancer ranks first among various malignant tumors, as high as 28%. There are more than 1.2 million new cases of lung cancer every year in the world, and 1.1 million deaths due to lung cancer every year. Compared with the 1970s, the mortality rate of lung cancer in my country has increas...

Claims

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Application Information

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IPC IPC(8): A61K31/704A61K31/69A61K31/573A61K31/365A61K31/282A61K31/196A61P35/00
Inventor 程永现周光飚梁恒兴刘莹何江波吕青刘永强李新春
Owner KUNMING INST OF BOTANY - CHINESE ACAD OF SCI
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