A kind of preparation method of tripterine derivative and its product and application

A technology for triptolide and derivatives is applied in the field of preparation of triptolide derivatives, and can solve the problems of poor water solubility, poor selectivity, complicated process and the like of triptolide

Active Publication Date: 2016-06-15
HUAQIAO UNIVERSITY
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  • Abstract
  • Description
  • Claims
  • Application Information

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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

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  • A kind of preparation method of tripterine derivative and its product and application
  • A kind of preparation method of tripterine derivative and its product and application
  • A kind of preparation method of tripterine derivative and its product and application

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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 8Individuals / mL) Cunninghamella blakesleana AS3.970 spore liquid, cultured 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; Add methyl jasmonate (MeJA, 0.78mmol / mL), betamethasone valerate (5mg / L) and carboxymethyl-β-cyclodextrin (BCD, 1.79mmol / mL), continue to cultivate for 12h, then add tripterine according to the inoculum amount of 5%, then continue to cultivate for 5 days, stop the culture, then centrifuge the filtrate at 8000r / min for 10min to remove the precipitate, and use an equal volume of the filtrate extracted with ethyl acetate for 3 times, the extract was evaporated to dryness, dissolved in 2 mL of acetone, and then separated by chromatography on a silica gel column. , and then successively use the volume ratio: 5:2, 2:3, 2:5, 0:5 petroleum ether: the eluent of dichloromethane, the volume ...

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 ...

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Abstract

The invention provides a preparation method of tripterylide derivatives and its products and applications. In the preparation method, tripterylide is used as a microbial metabolic drug, and a special elicitor is used to metabolize tripteryline to microorganisms to simultaneously obtain various, High-yield tripteryne derivatives based on the substitution and modification of tripteryne's hydroxyl group, reduction or carboxylation. The method of the invention is environmentally friendly, has strong selectivity and high yield, and can use microorganisms to prepare tripterylide derivatives on a large scale, and the prepared tripterylide derivatives have the characteristics of high efficiency and low toxicity, and can be actually used for tumors , viral diseases and neurological damage diseases, providing broad application prospects for tripterine 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 recorded 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 Taining The quality of Tripterygium wilfordii produced 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 activity, ...

Claims

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Application Information

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Patent Type & Authority Patents(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
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