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

Antitumor drug, synthetic method and application

A technology of anti-tumor drugs and synthesis methods, which is applied in the direction of anti-tumor drugs, drug combinations, pharmaceutical formulations, etc. It can solve the problems of unclear biological activity, solve the problems of solubility and transportability, simple synthesis method, and low biological toxicity Effect

Active Publication Date: 2019-11-01
SHANGHAI INST OF ONCOLOGY +1
View PDF2 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In recent years, as a chiral catalyst, helicene has a good application prospect in asymmetric synthesis and optoelectronic materials, but the research on its biological activity is not clear.

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
  • Antitumor drug, synthetic method and application
  • Antitumor drug, synthetic method and application
  • Antitumor drug, synthetic method and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] This embodiment relates to the method for preparing [4]helicenium, specifically comprising the following steps:

[0032] 4-Aza[4]helicene reference synthesis [M.J.E.Hewlins, R.Salter, Synthesis 2007,14,2164.].

[0033] 115 mg of 4-aza[4]helicene (0.5 mmol) was suspended in 3 mL of CHCl 3 and 1.5 mL of 1-bromopropane, and the mixture was stirred at 65° C. for 48 hours. As the reaction proceeded, a yellow solid was produced, and the solvent was removed by vacuum. Dissolve the solid in CH 2 Cl 2 and by adding Et 2 O precipitated and the solid was collected by centrifugation. The dissolution-precipitation-centrifugation process was repeated three times, and then the solid was kept in a vacuum oven to remove residual solvent. 123 mg of the product was obtained as a yellow solid with a yield of 70%.

[0034] Under the characterization results of the compound:

[0035] 1 H NMR (500MHz, DMSO-d6, 295K): δ10.10 (d, J = 8.6Hz, 1H), 9.61 (d, J = 5.7Hz, 1H), 8.89 (d, J = 8....

Embodiment 2

[0037] This embodiment involves detecting the selective killing effect of [4]helicenium on liver cancer cell lines, specifically including the following steps:

[0038] Hepatoma cell lines SK-Hep1, SMMC7721, HuH7, Hep G2 and liver cell line HL7702 in the logarithmic growth phase were inoculated in 96-well culture plates (1×10 4 pieces / hole). At 37°C, CO 2 Cultivate overnight in a cell incubator with a volume fraction of 5%. After the cells adhere to the wall, add 0-100 μg mL -1 The concentration of [4]helicenium was cultured for 24 hours, and 6 replicate wells were set for each concentration. After continuing to culture the cells for 24 hours, 10 μl of CCK-8 working solution was added to each well, and placed in an incubator for further incubation for 2 hours. The O.D value of each well at a wavelength of 450nm was detected on an enzyme-linked immunosorbent detector, and the survival rate of the cells was calculated. Cell survival rate (%)=(O.D value of experimental group-O...

Embodiment 3

[0041] This embodiment involves detecting the selective inhibitory effect of [4]helicenium on lung cancer cell lines, specifically including the following steps:

[0042] Liver cancer cell lines H1975, Calu-6, A549, H1299 and lung cell line Beas-2B in the logarithmic growth phase were inoculated in 96-well culture plates (1×10 4 pieces / hole). At 37°C, CO 2 Cultivate overnight in a cell incubator with a volume fraction of 5%. After the cells adhere to the wall, add 0-100 μg mL -1 The concentration of [4]helicenium was cultured for 24 hours, and 6 replicate wells were set for each concentration. After continuing to culture the cells for 24 hours, 10 μl of CCK-8 working solution was added to each well, and placed in an incubator for further incubation for 2 hours. The O.D value of each well at a wavelength of 450nm was detected on an enzyme-linked immunosorbent detector, and the survival rate of the cells was calculated. Cell survival rate (%)=(O.D value of experimental group-...

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 belongs to an antitumor drug, a synthetic method and an application, particularly relates to a helicene molecule 4-aza [4]helicenium ([4]helicenium) drug, a synthetic method and an antitumor application of the [4]helicenium drug. Aza[4]helicene is a derivative of condensed ring arene having a non-planar surface structure. The aza [4] helicene is subjected to quaternarization, so thatthe water-solubility of molecules and combining capacity of DNA can be obviously improved, various cancer of liver cancer, lung cancer, myoblastosis and the like can be efficiently inhibited, and attention needs to be paid on the situation that the [4]helicenium can kill tumor cells and tissue, and besides, does not have obvious toxicity to normal cells and tissue. The [4]helicenium has excellenttumor selectivity, and has good inhibition capability on reverse tolerance tumors of a conventional platinum chemotherapeutic drug. The [4]helicenium disclosed by the invention is simple in preparation method, good in water-solubility and obvious in selective tumor inhibition treatment effects, has broad spectrum, efficient and low-toxin properties, and particularly has broad application prospects in the field of preparation of traditional tumor chemotherapy drugs.

Description

technical field [0001] The invention belongs to the field of tumor chemotherapy, and relates to an antitumor drug, a synthesis method and an application thereof. The antineoplastic drug is 4-aza[4]helicenium quaternary ammonium salt ([4]helicenium). It is a broad-spectrum, high-efficiency, low-toxic tumor chemotherapy drug, synthesis and application. [4]helicenium can bind to DNA, and then prevent tumor cell DNA replication, induce tumor cell DNA damage and inhibit tumor cell DNA repair, and can efficiently kill liver cancer, lung cancer, leukemia and other tumors. The most important thing is that [4] helicenium has no obvious toxicity to normal cells and tissues while killing tumor cells and tissues, and has excellent selectivity. In view of the fact that [4]helicenium's mechanism of killing tumors is similar to that of traditional platinum-based chemotherapy drugs, [4]helicenium also has the ability to significantly inhibit cisplatin-resistant tumors. [4] The selective tu...

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): A61K31/473C07D221/18A61P35/00A61P35/02A61K33/243
CPCA61K31/473C07D221/18A61P35/00A61P35/02A61K33/243A61K2300/00
Inventor 刘培峰邱惠斌周雁干富伟
Owner SHANGHAI INST OF ONCOLOGY
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