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

Parthenolide derivatives, and preparation method and application thereof

A technology of parthenolide and derivatives, applied in the field of parthenolide derivatives and their preparation, can solve the problems of high morbidity and mortality, poor prognosis and the like

Inactive Publication Date: 2020-08-11
CHONGQING UNIV OF ARTS & SCI
View PDF0 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Despite the current great progress in the treatment of glioblastoma, its prognosis is poor and associated with excessive morbidity and mortality due to resistance to radiotherapy and chemotherapy

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
  • Parthenolide derivatives, and preparation method and application thereof
  • Parthenolide derivatives, and preparation method and application thereof
  • Parthenolide derivatives, and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0051] The structural formula of compound MCL is as follows:

[0052]

[0053] The preparation method of compound MCL is as follows: to 100mLCH 2 Cl 2 Add 86mg of p-toluenesulfonic acid (0.5mmol) to prepare p-toluenesulfonic acid solution, add 20mL CH 2 Cl 2 Add 3.5g parthenolide (14mmol) to prepare parthenolide solution, then add parthenolide solution dropwise in p-toluenesulfonic acid solution at room temperature, stir overnight at room temperature, and dissolve with 20mL saturated NaHCO 3 The reaction was quenched, and the resulting organic layer was washed with saturated brine (2 × 20 mL), anhydrous Na 2 SO 4 After drying and concentrating under reduced pressure, the obtained crude residue was recrystallized from acetone to obtain 3.2 g of light yellow crystalline solid, namely compound MCL, with a calculated yield of 91%.

[0054] 1 H NMR (400MHz, CDCl 3 )δ6.22(d, J=3.3Hz, 1H), 5.51(d, J=3.0Hz, 1H), 3.82(t, J=10.3Hz, 1H), 2.80–2.59(m, 3H), 2.40( dd,J=16.3,8.4Hz...

Embodiment 2

[0058] The structural formula of compound 1 is as follows:

[0059]

[0060] The preparation method of compound 1 is as follows:

[0061] At room temperature, 1.75 g of the compound MCL (mmol) prepared in Example 1 and 1.8 g of m-chloroperoxybenzoic acid (10.5 mmol) were added to 50 mL of CH 2 Cl 2 Stirring overnight, the resulting reaction mixture was sequentially washed with Na 2 SO 4 (2×30mL), NaHCO 3 (2×50mL) and saturated brine (2×30mL), washed with anhydrous Na 2 SO 4 After drying and concentration under reduced pressure, the obtained crude residue was recrystallized from acetone to obtain 1.3 g of crystalline solid, namely compound 1, and the calculated yield was 70%.

[0062] 1 H NMR (400MHz, CDCl 3 )δ6.20(d, J=3.3Hz, 1H), 5.48(d, J=3.0Hz, 1H), 4.05(t, J=10.4Hz, 1H), 2.81(s, 1H), 2.38–2.19( m,4H),2.04–1.82(m,4H),1.70–1.61(m,1H),1.48(s,3H),

[0063] 1.46–1.37(m,1H),1.30(s,3H). 13 C NMR (101MHz, CDCl 3 )δ169.62, 138.16, 119.55, 81.83, 79.71, 69.89, 62.19, ...

Embodiment 3

[0065] The structural formula of compound Arglabin is as follows:

[0066]

[0067] The preparation method of compound Arglabin is as follows:

[0068] At a temperature of 0°C, 264 mg of compound 1 (1.0 mmol) prepared in Example 2 was added to 5 mL of pyridine and stirred, and then 300 μL of phosphorus oxychloride was added to the obtained solution, stirred for 2 hours, and 30 mL of ether was added to obtain The organic layer was successively washed with NaHCO 3 and washed with saturated brine, anhydrous Na 2 SO 4 Dry and concentrate under reduced pressure to obtain a crude residue, which is separated and purified on a silica gel column to obtain 112 mg of compound Arglabin, and the calculated yield is 45%.

[0069] 1 H NMR (400MHz, CDCl 3 )δ6.15(d, J=3.3Hz, 1H), 5.58(s, 1H), 5.42(d, J=3.1Hz, 1H), 4.01(t, J=10.2Hz, 1H), 2.94(d, J=10.7Hz, 1H), 2.83–2.74(m, 1H), 2.29–2.11(m, 3H), 2.07–2.01(m, 1H), 1.99(d, J=7.9Hz, 3H), 1.88–1.82 (m,1H),1.55–1.45(m,1H),1.35(d,J=6.4Hz,3H...

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 relates to the technical field of organic synthesis, in particular to parthenolide derivatives, and a preparation method and application thereof. The 11 parthenolide derivatives are synthesized by taking feverfew as an initial main raw material through a series of chemical reactions, and the derivatives have certain anti-proliferative activity on glioblastoma cells. It is also provedin the invention that the deuterium-containing derivative DMAPT-D6 can obviously induce accumulation of active oxygen in glioblastoma cells, thereby leading to DNA damage in the glioblastoma cells. Furthermore, the DMAPT-D6 promotes death receptor-mediated exogenous apoptosis dependent on cysteine aspartase, indicating that DNA damage induced by the DMAPT-D6 can induce apoptosis of the glioblastoma cells. Thus, ROS accumulation caused by DMAPT-D6 treatment causes DNA damage, and then death receptor-mediated apoptosis is caused, so it is proved that the DMAPT-D6 with novel composition has treatment potential for treating glioblastoma and can be applied to preparation of medicines for treating glioblastoma.

Description

technical field [0001] The invention relates to the technical field of organic synthesis, in particular to parthenolide derivatives and their preparation methods and applications. Background technique [0002] Reactive oxygen species (Reactive oxygen species, ROS) is a short half-life, highly active, oxygen-containing by-products of aerobic metabolism, including superoxide, hydroxyl radicals and hydroxides. Cellular reactive oxygen species are mainly produced intracellularly by mitochondria, NADPH oxidase, peroxisomes, and endoplasmic reticulum. New data suggest that reactive oxygen species act as a double-edged sword in cells. Low levels of ROS are necessary for cell survival and proliferation; conversely, excess ROS can cause oxidative stress, leading to DNA damage, apoptosis, and necrosis. DNA damage is caused by chemical and physical factors, which can cause a series of complex processes, including cell cycle arrest, DNA repair, regulation of cellular checkpoints, init...

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): C07D307/93C07D493/06A61P35/00
CPCA61P35/00C07D307/93C07D493/06
Inventor 杨东林张亚军李勇秦红霞何刘军黄玖红
Owner CHONGQING UNIV OF ARTS & SCI
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