Preparation method for celastrol derivatives, products and application thereof

A technology of tripterygne and its derivatives, which is applied in the field of preparation of tripteryne derivatives, and can solve the problems of low yield, few applications, and poor selectivity of chemical synthesis methods

Active Publication Date: 2014-03-19
HUAQIAO UNIVERSITY
View PDF5 Cites 14 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although chemical modification provides broad prospects for the large-scale preparation of tripterine-related derivatives, the chemical synthesis method has disadvantages such as low yield, poor selectivity, many by-products, and complicated processes, and most of the current derivatives do not work. Compared with Tripterygium wilfordii, it is relatively weak, so it has certain limitations
[0004] Due to the extremely poor water-solubility of tripteryglide, its metabolites should be the most useful in vivo. Although the metabolites of tripteryne in vivo have been partially clarified, chemical methods can be used to directly obtain the same metabolites as tripterygium. The composition is relatively small, and on the other hand, the use of microorganisms with biomimetic metabolism directly transforms biological tripteryne through the special enzymatic action of microorganisms to produce a variety of in vivo metabolism and attenuated derivatives of tripteryne Good results have been achieved, but this method of metabolism has been rarely applied to tripterine, and no systematic reports have been seen yet

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
  • Preparation method for celastrol derivatives, products and application thereof
  • Preparation method for celastrol derivatives, products and application thereof
  • Preparation method for celastrol derivatives, products and application thereof

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0053] The present invention relates to a kind of preparation method of tripterine derivative, comprising the following steps:

[0054] Step 1: Take a transformed strain stored at 4°C and cultivated on a potato slant medium, place it in a constant temperature incubator at 25°C for 7 days, and blow off the spores on the slope with an appropriate amount of sterile water to make a single The concentration of the spore suspension was adjusted to 10 7 ~10 8 Individual / mL, acquired seed spore liquid;

[0055] Step 2: Inoculate the spore liquid obtained in Step 1 on the potato liquid medium with an inoculum amount of 100 mL or 5 mL, and cultivate it for 12 hours at a pH of 6.0, a temperature of 30°C ± 1°C, and a shaking speed of 200 r / min; press 0.1 ~4ug inoculation amount, add various combined elicitors in different proportions, continue to cultivate for 12 hours, then add tripterycin at an inoculation amount of 1~10ug, and then continue to culture for 5 days, detect various tript...

Embodiment 1

[0094] Example 1: Preparation of tripterine derivatives

[0095] 1, Preparation of 6-hydrotripterine

[0096] Inoculate 5 mL (10 8Cunninghamella blakesleana (Cunninghamella blakesleana) AS3.970 spore liquid, cultivated for 12 hours at a pH of 6.0, at a temperature of 30°C±1°C, and at a shaking speed of 200r / min; inoculum size of 0.2ug , adding methyl jasmonate (MeJA, 0.78mmol / mL), betamethasone valerate (5mg / L) and carboxymethyl-β-cyclodextrin ( BCD, 1.79mmol / mL), after continuing to cultivate for 12h, add tripterine according to the inoculum amount of 5%, then continue to cultivate for 5 days, stop the cultivation, then centrifuge the filtrate at 8000r / min for 10min to remove the precipitate, the filtrate Extract with an equal volume of ethyl acetate for 3 times, evaporate the extract to dryness, dissolve it with 2 mL of acetone, and then separate it with a chromatographic silica gel column. Elution is clean, and then successively use petroleum ether: dichloromethane eluen...

Embodiment 2

[0140] Embodiment two, pharmacodynamics evaluation experimental example

[0141] In the following experimental examples, the test sample is provided by the preparation method embodiment of the present invention, and the precursor compound tripterine is used as a positive control.

[0142] 1. The growth inhibitory effect of 8 compounds of the present invention on human lung cancer cell A549 cells cultured in vitro

[0143] Methods: Human A549 lung cancer cells were cultured in DMEM medium (Gibco, USA) containing 10% fetal bovine serum at 37°C, 5% CO 2 , tumor cells 0.7x10 4 / well was inoculated in a 96-well plate, and after 24 hours, the compound diluted with dimethyl sulfoxide (200uM) and PBS solution was added to make the final concentration of the culture medium 10 -4 、10 -5 、10 -6 、10 -7 、10 -8 M, after 72 hours of treatment, discard the culture medium, fix the cells with 10% cold trichloroacetic acid, stain with sulforhodamine B (SRB) solution, wash away the unbound ...

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

No PUM Login to view more

Abstract

The invention provides a preparation method for celastrol derivatives, products and application thereof. The preparation method takes celastrol a microbial metabolic drug, and enables microorganisms to metabolize celastrol through a special elicitor, so that a plurality of high yield celastrol derivatives based on celastrol's hydroxyl, reduction or carboxylation and other substitution modification can be obtained at the same time. Being green and environment friendly, the method provided by the invention has strong selectivity and high yield, and can make large-scale use of microorganisms to prepare celastrol derivatives. The prepared celastrol derivatives have the characteristics of high efficiency and low toxicity, etc., and can practically be used for treatment of tumors, viral diseases and nerve injury diseases, thus providing broad application prospects for celastrol derivatives.

Description

【Technical field】 [0001] The invention relates to a preparation method of tripterine derivatives as well as products and applications thereof. 【Background technique】 [0002] Tripterygium wilfordii Hook.F., a plant of the Euonymus family, was collected in "Southern Yunnan Materia Medica", and its production areas are mainly distributed in southern China, including Zhejiang, Hunan, Anhui, Yunnan, Fujian and Taiwan, among which Fujian The quality of Tripterygium wilfordii produced in Taining is the best [1] . Celastrol (CS), which belongs to quinone methyl triterpenoids, is one of the main active ingredients of Tripterygium wilfordii. Its anti-cancer, anti-inflammatory, especially in the treatment of nervous system diseases include: Alzheimer Alzheimer's disease (Alzheimer's disease, AD), Parkinson's disease (PD), Huntington's degenerative disease (HD) and spinal cord injury, amyotrophic lateral sclerosis (ALS) and other diseases have shown outstanding pharmacological activi...

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): C12P33/00C12P33/20C07J63/00A61P35/00A61P35/02A61P31/18A61P1/16A61P31/22A61P31/16A61P31/20A61P25/28A61P25/16A61P25/14A61P25/00C12R1/645C12R1/685C12R1/785C12R1/80
Inventor 张景红谢深霞叶龙飞
Owner HUAQIAO UNIVERSITY
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap