Application of ruthenium complex in antitumor drug preparation

A technology of anti-tumor drugs and ruthenium complexes, which is applied in the field of anti-tumor drugs, can solve the problems of poor recognition ability between normal cells and tumor cells, failure of treatment and treatment, toxic and side effects of tumor patients, etc., and achieve good killing effect in vivo and in vitro Effect

Inactive Publication Date: 2014-02-26
SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0002] Due to the excellent cytotoxicity of traditional chemotherapy drugs, chemotherapy has become an important means of clinical treatment of tumor diseases. However, due to its poor ability to recognize the difference between normal cells and tumor cells, it has caused serious harm to tumor patients in clinical applications. Toxic side effects, which are the leading cause of treatment discontinuation and treatment failure

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  • Application of ruthenium complex in antitumor drug preparation
  • Application of ruthenium complex in antitumor drug preparation
  • Application of ruthenium complex in antitumor drug preparation

Examples

Experimental program
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Effect test

Embodiment 1

[0028] Example 1 Mitochondria targeting

[0029] Take the HeLa cells in the logarithmic growth phase and adjust the concentration to 1 × 10 4 / mL, inoculate into 35mm cell culture dish, when the cells grow to 60% confluence, add 10 μM ruthenium complex and mitochondria-specific fluorescent probe Mito-Tracker, incubate for 15 minutes, use a Zeiss inverted fluorescence microscope (Zeiss Axio Observer D1 ) to detect the intracellular localization of ruthenium complexes, the experimental results are as follows figure 1 As shown (A is the bright field, B is the ruthenium complex (red fluorescence), C is the mitochondria-specific fluorescent probe (green fluorescence), D is the overlay of B and C). Experiments show that, figure 1 -D shows that the red fluorescence emitted by the ruthenium complex and the green fluorescence emitted by the mitochondria-specific fluorescent probe are superimposed to present orange fluorescence, which proves that the ruthenium complex can be targeted ...

Embodiment 2

[0030] Example 2 Determination of antitumor activity of ruthenium complexes in vitro

[0031] The screened cell lines include: tumor cells HeLa, A-549, BEL-7402, HepG2, MCF-7, and cisplatin-resistant strain CP / R-A54. The determination adopts bromide tetrazolium blue (MTT) method, its principle is: bromide tetrazolium blue [MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide] is A dye that can accept hydrogen atoms. The dehydrogenase associated with NADP in the mitochondria of living cells can convert yellow MTT into insoluble blue-purple formazan in cells, while dead cells have no such function. After dissolving formazan with dimethyl sulfoxide (DMSO), measure the optical density value with a microplate reader at a certain wavelength, and the survival rate of the cells can be quantitatively measured. Experimental procedure: Take HeLa cells in the logarithmic growth phase and adjust the cell density to 5x10 4 cells / mL, inoculated in 96-well culture plate, 200 m...

Embodiment 3

[0036] Example 3 Ruthenium complexes induce tumor cell apoptosis

[0037] The measurement uses flow cytometry Annexin-V staining method, the principle of which is: Phosphatidylserine (Phosphatidylserine, PS) is normally located on the inner side of the cell membrane, but in the early stage of apoptosis, PS can flip from the inner side of the cell membrane to the surface of the cell membrane, exposed to the extracellular environment. Annexin-V is a Ca 2+ Dependent phospholipid-binding protein, which can specifically bind to PS with high affinity. Annexin-V was labeled with fluorescein (FITC), and the labeled Annexin-V was used as a fluorescent probe to detect the occurrence of apoptosis by flow cytometry.

[0038] Experimental procedure: HeLa cells in the logarithmic growth phase were treated with 5 x 10 4 Cells / mL were seeded in 6-well plates, 2 mL per well, placed at 37°C, 5% CO 2 After culturing in a saturated humidity incubator for 24 hours, different concentrations of ...

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Abstract

The invention discloses an application of ruthenium complex in antitumor drug preparation. The ruthenium complex is a delta configuration in a chiral molecule, and the structure formula is delta-[Ru(bpy)2(HPIP)](C1O4)2, wherein, HPIP is 2-(2-hydroxyphenyl) imidazole [4, 5-f] [1,10] phenanthroline. The ruthenium complex has strong inhibition effects for human tumor cells HeLa, A-549, BEL-7402, HepG2, MCF-7 and DDP-resistant line CP / R-A549, and has little toxicity for human normal hepatocyte LO2, and can induce the tumor cells to generate apoptosis by mitochondria apoptosis pathway. According to in vivo experiment of animals, ruthenium complex can substantially inhibit growth of subcutaneous human derived transplantation tumor of nude mouse, and under the treatment dosage, no toxicity relative to the complex is detected, thereby the product can be applied to preparation of novel antineoplastic active medicament whose target is mitochondria.

Description

technical field [0001] The invention belongs to the technical field of antitumor drugs, and in particular relates to the application of a ruthenium complex in the preparation of antitumor drugs. Background technique [0002] Due to the excellent cytotoxicity of traditional chemotherapy drugs, chemotherapy has become an important means of clinical treatment of tumor diseases. However, due to its poor ability to recognize the difference between normal cells and tumor cells, it has caused serious harm to tumor patients in clinical applications. Toxic side effects, which are the main cause of treatment discontinuation and treatment failure. Therefore, it is more and more urgent to develop anti-tumor drugs with strong targeting and low side effects. [0003] Compared with other metal anticancer drugs, ruthenium (Ruthenium) complexes have higher cytotoxicity and less toxic side effects, showing broad development prospects, especially the three ruthenium complexes have entered pha...

Claims

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Application Information

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IPC IPC(8): A61K33/24A61P35/00
Inventor 巢晖王金全计亮年
Owner SUN YAT SEN UNIV
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