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class c 19 Diterpene alkaloids and their uses

A technology of uses and drugs, applied in the field of medicine, can solve the problems of limited treatment methods, fluctuating symptoms, complex pathological mechanisms of neurodegenerative diseases, etc.

Active Publication Date: 2021-11-05
SOUTHWEST JIAOTONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] Due to the complex pathological mechanism of neurodegenerative diseases, the existing treatment methods are very limited
At present, PD is treated clinically symptomatically, and there is no effective method to restore degenerated neurons; for the treatment of AD, the FDA has so far only approved 5 symptomatic drugs, and drugs that affect the course of the disease are still in the preliminary research stage
Not only that, most drugs for the treatment of neurodegenerative diseases have obvious side effects. For example, levodopa, which is the basic drug for PD treatment, may have adverse reactions such as symptom fluctuations, on-off phenomena, and movement disorders, which limit its wide use

Method used

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  • class c <sub>19</sub> Diterpene alkaloids and their uses
  • class c <sub>19</sub> Diterpene alkaloids and their uses
  • class c <sub>19</sub> Diterpene alkaloids and their uses

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0085] Preparation of compounds of the invention one embodiment

[0086] Take empty plant stems Aconitum Aconitum Aconitum apetalum. 4.3kg roots, at room temperature, the dried root of Aconitum empty stems extracted four times with 95% ethanol, each time soaked for 4 days, concentrated under reduced pressure to give extract (360g).

[0087] Extract dissolved in water with 50 deg.] C, first with 10% w / w solution of hydrochloric acid to pH 3.0, followed by petroleum ether, extracted with ethyl acetate. Then an aqueous solution and then 24% w / w concentrated aqueous ammonia to adjust the pH to 9.4, then extracted with methylene chloride, methylene chloride and concentrated under reduced pressure portion of the total alkaloids to give (40g).

[0088] Using normal phase silica gel column chromatography by CH 2 CL 2 : CH 3 OH (1: 0-0: 1) gradient elution, detected by thin layer chromatography, the sequential fractions were combined, successively to give eight parts: A 1 (900mg), A 2 ...

experiment example 1

[0106] Inhibitory effect of compound of Example 1 of the present invention on oxidative damage in SH-SY5Y Cells

[0107] The frozen in liquid nitrogen in SH-SY5Y cell line removed rapidly shaking water bath at 37 ℃, so as to melt. Removed, moved to a clean bench, sterilized with 75% alcohol scrubbing, the cell suspension was taken out under sterile conditions, sterilized injection tube, and then add an appropriate amount of 10% FBS-containing DMEM complete, 1000r / min, centrifuge 5min, supernatant was aspirated, the culture solution was centrifuged plus 1 times. SH-SY5Y cells with 10% fetal bovine serum DMEM complete containing diluted to 1mL per 1 × 10 5 A cell suspension of cells inoculated in cell culture flask. After completion of inoculation, the flasks were placed in 37 ℃, 5% CO 2 Conditions CO 2 Incubator. The medium was changed once a day, after a conventional culture, i.e. passages 3d 1 times.

[0108] The SH-SY5Y cells per 1mL containing 8 × 10 5 The concentration of ce...

experiment example 2

[0113] Experimental Example Compound 2 of the present invention to MPP + Apoptosis inducing protective SH-SY5Y Cells

[0114] SH-SY5Y cells were cultured in DMEM medium containing 10% fetal bovine serum Basic, incubated at 37 ℃, 5% CO 2 , Humidified incubator until the cells are grown to an appropriate density, trypsin digestion and passage. SH-SY5Y cells were seeded in 96-digested cell culture plate wells, until adherent cells, added at a concentration of MPP 1.8mM + And a test sample dissolved in DMSO Apetaldine A, Apetaldine B, Apetaldine C, Apetaldine D, Apetaldine E (administered at a concentration shown in Table 4), the control group, only PBS control was added. Three parallel wells of each sample is provided, using an automatic spectrophotometer calibration inhibitory activity of each sample was measured by the method of Ellman, protection rate calculation, different concentrations of Apetaldine A, Apetaldine B, Apetaldine C, Apetaldine D, Apetaldine E of protective effects...

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Abstract

The invention discloses the compound represented by formula I, or its optical isomer, or its pharmaceutically acceptable salt, or its crystal form, or its solvate. Drug efficacy experiments show that the compound of the present invention has a good protective effect on nerve cells, can effectively inhibit the damage caused by oxidative stress to nerve cells, and inhibit the apoptosis of nerve cells. The effect is remarkable, and there is no obvious cytotoxicity, and the safety is high. , is a potential drug for the prevention and treatment of neurodegenerative diseases such as Parkinson's disease. The compound of the invention can be obtained by extracting and separating from plants of the genus Aconitum, has a wide range of drug sources, and has broad clinical application prospects and market prospects.

Description

Technical field [0001] The present invention relates to a class of novel structures. 19 Diterici biocarns and their use belong to the medical field. Background technique [0002] Neurodegenerative diseases are caused by neurons and (or) loss of myelin, deteriorated over time, resulting in dysfunction. Clinically, Alzheimer's disease (AD), Parkinson's disease (PD), Huntington (HD), myocyteramid side rigidation (ALS). The cerebral pathological changes in this type of disease are mainly lost in a large number of neurons caused by apoptosis, or the nervous system has no significant reduction in cells, but the structure and function of neuronal cells, degenerative degeneration. With the increasing increase in the elderly population in my country, the incidence of neurodegenerative diseases has also increased year by year. However, there are currently only several few drugs available for the treatment of neurodegenerative diseases. [0003] A large number of studies have shown that the...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D221/22A61K31/439A61P25/00A61P25/28A61P25/14A61P25/16
CPCA61K36/714C07D221/22
Inventor 周先礼张吉发高峰黄帅单连海
Owner SOUTHWEST JIAOTONG UNIV