Metallic supermolecule compound for inhibiting telomere enzymatic activity, using method and uses thereof

A supramolecular compound, telomerase technology, applied in the direction of organic active ingredients, iron organic compounds, nickel organic compounds, etc., can solve the problems of unsatisfactory curative effect, endangering human life and health, serious problems, etc.

Inactive Publication Date: 2008-09-24
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

For the treatment of cancer, people have developed a variety of surgical, medical and radiological anti-cancer methods and combined for cancer treatment, and have made considerable progress, but for the most serious threat to human life and health, accounting for more than 90% of malignant tumors Treatment of solid tumors fails to achieve satisfactory results

Method used

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  • Metallic supermolecule compound for inhibiting telomere enzymatic activity, using method and uses thereof
  • Metallic supermolecule compound for inhibiting telomere enzymatic activity, using method and uses thereof
  • Metallic supermolecule compound for inhibiting telomere enzymatic activity, using method and uses thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] Example 1 Method for Inhibiting Telomerase Activity by Metallosupramolecular Compounds

[0038] cell culture

[0039] COC1 and K562 cells at 37°C, 5% CO 2 The culture medium is IMDM plus 10% fetal bovine serum, and the medium is changed every two days, and the cells in the logarithmic growth phase are taken for experiments.

[0040] Taq polymerase activity assay

[0041] For the detection method of telomerase activity based on the TRAP method, in order to eliminate the false positive results caused by the inhibition of the sample on the Taq enzyme activity, it is necessary to detect the influence of the sample on the Taq polymerase activity. Add: oligo DNA 20ng, Primers P1 and P2 each 40pmol, dNTP 10pmol, 10×ExTaq buffer 5ul, ExTaq polymerase 2.5U, metal nickel supramolecular compound P or M, or metal iron supramolecular compound P or M concentration are 2umol / l, supplemented Bacterial water to 50ul, without metal supramolecular compounds as the control group, mix we...

Embodiment 2

[0056] Example 2 Metal supramolecular compound promotes tumor cell senescence

[0057] Detection of cellular senescence

[0058] Cell senescence was detected by SA-b-galactosidase method. The above cells were washed with PBS, fixed in 2% formaldehyde / 0.2% glutaraldehyde at room temperature for 5 minutes, washed with PBS, added β-Gal staining solution and incubated at 37°C for 16 hours. The formula of β-Gal dye solution is 1mg / ml5-bromo-4-chloro-3-indolyl-β-D-galactoside, 40mmol / l citric acid / sodium phosphate, pH=6, 5mmol / l potassium ferrocyanide, 5mmol / l potassium ferricyanide, 150mmol / l sodium chloride, 2mmol / l magnesium chloride. Optical microscope inspection and photography.

[0059] P16, P21 protein content detection

[0060] The changes of P16 and P2l protein content after the compounds acted on the cells were detected by Western blotting. Specific steps: After washing with PBS, add lysis buffer to the cells, the formula is 10mmol / l Tris-HCl, pH 7.4, 5mmol / l MgCl 2 ...

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Abstract

The present invention relates to a metal supramolecular compound that can be used for inhibiting the activity of telomerase, a method and an application thereof. The metal supramolecular compound has a structure as shown in the formula I; wherein, the formula III is Ni<2+> or Fe<2+>; the molecular formula of ligand is C25H20N4; and the ligand has a structure as shown in II. The metal supramolecular compound comprises a pair of isomers with corresponding structures, P and M. The metal supramolecular compound can inhibit the proliferation of the active cells of the telomerase, such as the proliferation of tumor cells, and can induce the aging of the tumor cells. So the metal supramolecular compound that can be used for inhibiting the activity of the telomerase can be used for preparing antineoplastics.

Description

field of invention [0001] The invention relates to a metal supramolecular compound for inhibiting telomerase activity and its usage and application. Background of the invention [0002] Cancer is the second largest killer after cardiovascular disease worldwide. For the treatment of cancer, people have developed a variety of surgical, medical and radiological anti-cancer methods and combined for cancer treatment, and have made considerable progress, but for the most serious threat to human life and health, accounting for more than 90% of malignant tumors The treatment of solid tumors has not achieved satisfactory results. Researchers are becoming more and more aware that in order to improve the curative effect of tumor treatment and develop effective methods to prevent and treat cancer, they must start with the mechanism of tumor occurrence and development in order to achieve new breakthroughs. [0003] Telomere is a special structure existing at the end of chromosome DNA i...

Claims

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Application Information

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IPC IPC(8): C07D213/53C07F15/02C07F15/04A61K31/444A61K31/555A61P35/00
Inventor 曲晓刚付满良于海佳
Owner CHANGCHUN INST OF APPLIED CHEMISTRY - CHINESE ACAD OF SCI
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