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Application of Chiral Metal Supramolecular Compounds in the Preparation of Anti-tumor Stem Cell Drugs

A technology of supramolecular compounds and stem cells, which is applied in the application field of chiral metal supramolecular compounds in the preparation of anti-tumor stem cell drugs, can solve the problem of poor selectivity of telomeric G-four-strand DNA, and achieve strong selectivity and short time , the effect of inhibiting the properties of tumor stem cells

Active Publication Date: 2019-11-19
CHANGCHUN INST OF APPLIED CHEMISTRY - CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, these compounds generally have the disadvantage of poor selectivity to telomeric G-quadruplex DNA

Method used

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  • Application of Chiral Metal Supramolecular Compounds in the Preparation of Anti-tumor Stem Cell Drugs
  • Application of Chiral Metal Supramolecular Compounds in the Preparation of Anti-tumor Stem Cell Drugs
  • Application of Chiral Metal Supramolecular Compounds in the Preparation of Anti-tumor Stem Cell Drugs

Examples

Experimental program
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Effect test

Embodiment 1

[0028] The synthesis of embodiment 1Ni-P and Ni-M

[0029] Mix 2-pyridinecarbaldehyde and 4,4'-methylenediphenylamine in an ethanol solvent at a molar ratio of 2:1, react at room temperature for 2 hours, then filter with suction to obtain a light yellow product, and dry it in vacuum to obtain a compound with the structural formula I. body; the ligand and metal chloride NiCl 2 Mix according to the molar ratio of 3:2, heat and reflux in methanol for 6h, concentrate the reaction solution, and perform chiral cellulose column separation to obtain Ni-P and Ni-M. The compound structural formula of Ni-P and Ni-M is as follows figure 1 Shown in panels A and B.

Embodiment 2

[0030] Example 2 Enrichment culture and identification of breast cancer stem cells

[0031] MDA-MB-231 and MCF-7 cells were inoculated into DMEM / F12 medium at a density of 5000 cells / ml, to which 20ng / ml basic fibroblast growth factor, 20ng / ml human recombinant epithelial growth factor, 4μg / ml heparin, 1% streptomycin and penicillin, and culture in a 6-well ultra-low adhesion culture plate, after inoculation, place the culture plate at 37°C, 5% CO 2 , in a humid incubator, and after 7 days, the formed microspheres were digested into single cells with 0.25% trypsin, and then cultured for the second time at a cell density of 5000 cells / ml. After 7 days, the microspheres were collected, and the same digested into single cells.

[0032] Will 1×10 6 Each cell was dispersed in 100 μl of PBS buffer, PE-labeled CD24 antibody and APC-labeled CD44 antibody were added to it, incubated at room temperature for 30 min, then washed twice with PBS, resuspended in 500 μl PBS, and finally an...

Embodiment 3

[0034] Example 3 Effects of Ni-P and Ni-M on Telomerase Activity in Tumor Stem Cells

[0035] 5,000 breast cancer stem cells were inoculated into 6-well ultra-low adhesion culture plates, and Ni-P and Ni-M were added at the same time. The concentration gradients of Ni-P and Ni-M were: 0.16, 0.32, 0.64, 1.28, 2.56, 5.12μM, cells were collected after 7 days for TRAP detection.

[0036] The TRAP experiment method is as follows: collect cells by centrifugation, wash twice with pre-cooled PBS, add 100 μL CHAPS lysate (10mM Tris HCl, pH 7.5, 1mM MgCl 2 , 1mM EGTA, 0.1mM PMSF, 0.1mMmercaptoethanol, 0.5% CHAPS, 10% glycerol), incubate on ice for 30min, centrifuge at 12000rpm, 4°C for 20min, and collect the supernatant as the crude telomerase extract. Add 3 μg of telomerase extract to the RNA inactivation system, which includes 1×TRAP buffer (20mM Tris HCl pH 8.3, 1.5mM MgCl 2 , 63mM KCl, 0.005% Tween 20, 1mMEGTA, BSA 0.1mg / ml), 0.1μg TS primer, 1mM dNTP, extended at 30°C for 60min. ...

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Abstract

The invention provides an application of a chiral metal supramolecular compound in the preparation of anti-tumor stem cell medicine, belonging to the field of chiral metal supramolecular compounds. The chiral metal supramolecular compound is [Ni 2 L 3 ] 4+ The P enantiomer, the P enantiomer is composed of two Ni 2+ Combined with three ligands of the structural formula I through coordination bonds to form a six-coordinated right-handed dinuclear metal triple helical cylinder structure. As an anti-tumor stem cell compound, Ni-P of the present invention has chiral selectivity, strong selectivity to telomere G-four-stranded DNA, can simultaneously inhibit the growth of tumor stem cells and tumor cells, and is more effective than other telomerase inhibitors. The time required to kill tumor stem cells is short, and the toxicity to normal somatic cells is small.

Description

technical field [0001] The invention belongs to the field of chiral metal supramolecular compounds, in particular to the application of a chiral metal supramolecular compound in the preparation of anti-tumor stem cell drugs. Background technique [0002] Cancer stem cells are the source of tumor metastasis and recurrence. Traditional antineoplastic drugs can kill most tumor cells and reduce tumor volume, but cannot eliminate tumor stem cells. The surviving tumor stem cells rapidly proliferate and differentiate to form new tumor cells, so that the patient eventually dies of tumor metastasis or recurrence. With the rapid development of targeted chemotherapy, many anti-tumor stem cell compounds targeting different targets have been discovered, such as compounds targeting various kinases, mitochondria or tumor microenvironment. However, these compounds (such as oligomycin A, perifoxine, repertaxin) have weak selectivity to tumor stem cells, and have strong toxic side effects o...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/555A61P35/00
CPCA61K31/555
Inventor 曲晓刚秦洪双
Owner CHANGCHUN INST OF APPLIED CHEMISTRY - CHINESE ACAD OF SCI
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