Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Sesquiterpene lactone compounds, preparation method thereof and application to preparation of NPC (nasopharyngeal carcinoma) preventing and treating drugs

A technology of ester compounds and sesquiterpenes, applied in the field of compounds and medicines, can solve the problems of easy metastasis and recurrence, no specific anti-nasopharyngeal carcinoma, poor patient compliance with treatment, etc., so as to inhibit the proliferation of nasopharyngeal carcinoma cells and promote the The effect of cancer cell apoptosis and high anti-nasopharyngeal carcinoma activity

Active Publication Date: 2019-12-13
SUN YAT SEN UNIV
View PDF3 Cites 4 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although concurrent chemoradiotherapy based on cisplatin is the standard treatment for nasopharyngeal carcinoma, more than two-thirds of nasopharyngeal carcinoma patients are already in locally advanced stage at the time of diagnosis due to the hidden location of nasopharyngeal carcinoma, which is prone to metastasis and The characteristics of relapse, and the severe side effects caused by cisplatin make the patient's treatment compliance poor
Nasopharyngeal carcinoma is a highly chemosensitive tumor. So far, there are no specific anti-nasopharyngeal carcinoma drugs in clinical practice, all of which are broad-spectrum anticancer drugs, including cisplatin, cyclophosphamide, nitrogen mustard and 5- Fluorouracil, etc., so there is an urgent need for highly effective and low-toxic anti-nasopharyngeal cancer drugs

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Sesquiterpene lactone compounds, preparation method thereof and application to preparation of NPC (nasopharyngeal carcinoma) preventing and treating drugs
  • Sesquiterpene lactone compounds, preparation method thereof and application to preparation of NPC (nasopharyngeal carcinoma) preventing and treating drugs
  • Sesquiterpene lactone compounds, preparation method thereof and application to preparation of NPC (nasopharyngeal carcinoma) preventing and treating drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0050] Compounds XF-1 to XF-18 were prepared from Inula flower (Euphorbia antiquorum L.).

[0051] The dried inflorescences of Inula inula were extracted three times with 95% ethanol water at room temperature, each time for 72 hours, and the extract was concentrated under reduced pressure to obtain a crude extract. The crude extract was suspended in water, extracted with ethyl acetate, and concentrated under reduced pressure to obtain the ethyl acetate fraction, which was chromatographed on a silica gel column (100-200 mesh) and eluted with petroleum ether / ethyl acetate gradient (9:1, 8:2,2:1,1:2,0:1), after TLC detection, it was divided into 3 components (A-C). Part B (54 g) was subjected to reverse phase column chromatography, eluting with methanol / water (50%-100%) to obtain seven fractions Fr.B1-7. Fr.B2 was eluted with Sephadex LH-20 with dichloromethane / methanol (1:1) to obtain compounds XF-1 (120mg), XF-2 (2.3g), XF-3 (50mg), XF-4 (20mg). Fr.B3 was separated by HPLC t...

Embodiment 2

[0053] Preparation of Ergolide Derivatives XF2-1~XF2-30

[0054] Synthetic route a: at room temperature, the compound Ergolide (XF2, 10mg, 0.03mmol) and the catalytic equivalent of 10% Pd / C were dissolved in 2mL of methanol, in H 2 Under conditions, stir for 1h. The completion of the reaction was monitored by low-resolution mass spectrometry, the device was removed, Pd / C was removed by filtration with a microporous membrane, and concentrated under reduced pressure to obtain white solid XF2-1 (10 mg, 100%).

[0055] b: Dissolve the compound Ergolide (50mg, 0.17mmol) in tetrahydrofuran (2mL), stir in an ice bath, add 5e.q lithium hydroxide (20mg, 0.85mmol) dissolved in 1mL ethanol / water (1 / 1), TLC Monitor the reaction. After the reaction is complete, spin dry and add an appropriate amount of saturated saline, add concentrated hydrochloric acid dropwise in an ice bath, and precipitate a white solid Carpesiolin (XF-1, 37mg, 85%)

[0056] c: Put the compound Ergolide (20mg, 0.08m...

Embodiment 3

[0064] Prepare formula (I) earlier by the method of embodiment 1 and 2, add water for injection according to routine, fine filter, potting sterilization makes injection solution.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

PropertyMeasurementUnit
pore sizeaaaaaaaaaa
Login to View More

Abstract

The invention discloses sesquiterpene lactone compounds, a preparation method thereof and an application to preparation of NPC (nasopharyngeal carcinoma) preventing and treating drugs. The structuralformula of the sesquiterpene lactone compounds is presented as the formula (I); and the sesquiterpene lactone compounds have higher anti-NPC activity, IC50 of the most compounds is 10.0 [mu] M or lower, and particularly, IC50 of the anti-NPC activity of the compound XF2-30 reaches 0.40 [mu] M. The efficacy evaluation for the compounds shows that the compounds inhibit NPC proliferation, promote carcinoma cell apoptosis, induce autophagy and have an obvious inhibition effect on migration and invasion of NPC cells. In a transplantation tumor experiment of a NPC nude mouse, the inhibition ratio reaches 53% under the dosage of 7.5 mg / kg and is comparable with that of positive control cis-platinum (under the dosage of 5 mg / kg), an in-vivo safety experiment also confirms safety of the compounds,and the compounds can be applied to preparation of the NPC preventing and treating drugs.

Description

technical field [0001] The invention relates to the technical field of compounds and medicines, in particular to a sesquiterpene lactone compound and its preparation method and its application in the preparation of medicines for preventing and treating nasopharyngeal carcinoma. Background technique [0002] Nasopharyngeal carcinoma (NPC) is a common head and neck tumor in South China and Southeast Asia, and Guangdong has the highest incidence rate, so it is also called "Guangdong cancer". The occurrence of nasopharyngeal carcinoma is related to Epstein-Barr Virus (EBV) infection, environmental factors and genetic factors. Although concurrent chemoradiotherapy based on cisplatin is the standard treatment for nasopharyngeal carcinoma, more than two-thirds of nasopharyngeal carcinoma patients are already in locally advanced stage at the time of diagnosis due to the hidden location of nasopharyngeal carcinoma, which is prone to metastasis and The characteristics of relapse, and...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): C07D307/93C07D405/12C07D417/12C07D409/12A61K31/365A61K31/443A61K31/4436A61K31/4709A61K31/498A61P35/00
CPCA61P35/00C07D307/93C07D405/12C07D409/12C07D417/12
Inventor 顾琼程燕芳尹智勇徐峻
Owner SUN YAT SEN UNIV
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com