Preparation method of ruthenium complex and acquired immune deficiency syndrome virus reverse transcriptase inhibition application of ruthenium complex

A technology of HIV and complexes, applied in ruthenium organic compounds, antiviral agents, pharmaceutical formulations, etc., can solve the problems of reduced affinity and high affinity of the active site of the substrate, and achieve good water solubility, stability, and stable structure , the effect of strong HIV reverse transcriptase inhibitory ability

Inactive Publication Date: 2019-01-18
YUNNAN UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Their affinity for the "enzyme-substrate" complex is higher than that for the enzyme, and the interaction with reverse transcriptase can cause a change in the configuration of the enzyme, thereby reducing the affinity of the active site of the substrate

Method used

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  • Preparation method of ruthenium complex and acquired immune deficiency syndrome virus reverse transcriptase inhibition application of ruthenium complex
  • Preparation method of ruthenium complex and acquired immune deficiency syndrome virus reverse transcriptase inhibition application of ruthenium complex
  • Preparation method of ruthenium complex and acquired immune deficiency syndrome virus reverse transcriptase inhibition application of ruthenium complex

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] Example 1 Preparation of polypyridine ruthenium complexes

[0034] 1. Preparation of polypyridine ruthenium complex Ru1:

[0035] according to figure 1The indicated pathways were synthesized. Reflux 4,4'-dimethyl-2,2'-bipyridine (1.5 g, 8 mmol) and selenium dioxide (887.68 mg, 8 mmol) in 100 ml 1,4-dioxane for 24 h , cooled to room temperature, the black solid was filtered off, and the solvent was distilled off to obtain a white solid. The solid was stirred and dissolved with 100 ml of ethyl acetate, and the insolubles were filtered off. The filtrate was washed three times with 20 ml of 1.0 M sodium carbonate solution, and the organic phase was extracted three times with 50 ml of 0.3 M sodium metabisulfite solution. The pH of the sodium solution was adjusted to 10, extracted four times with 20 ml of chloroform, the organic phases were combined, dried over anhydrous sodium sulfate, and the solvent was evaporated to obtain a crude product. The crude product was purif...

Embodiment 2

[0042] Example 2 Electrophoresis experiment of polypyridine ruthenium complex recognizing HIV TAR RNA

[0043]In the 1:1 HIV TAR RNA (Shanghai Sangon Biotechnology) and TAR binding protein tat (Shanghai Qiangyao Biotechnology) system, adding different concentrations of polypyridine ruthenium complexes, polyacrylamide gel electrophoresis experiments were performed, 4S Gel Red staining, gel imaging on FluorChemFC3. like image 3 As shown, with the increase of the concentration of the polypyridine ruthenium complex, the TAR RNA bound to tat protein gradually decreased, and finally disappeared completely, indicating that the ruthenium complex competed with tat for binding to the same site. The ability of the complex to bind to TAR RNA is Ru1>Ru2>Ru3>Ru4, indicating that as the distance between the TAR RNA recognition group and the center of the ruthenium complex (the length of the connecting chain) increases, the ability of the complex to bind to TAR RNA will decrease. . On the...

Embodiment 3

[0044] Example 3 Enzyme-linked immunosorbent assay of polypyridine ruthenium complex inhibiting HIV reverse transcriptase

[0045] Using the Roche kit (Reverse Transcriptase Assay, colorimetric), the inhibitory activity of the polypyridine ruthenium complex prepared in the present invention on the recombinant HIV-1 HIV reverse transcriptase was determined based on the enzyme-linked immunosorbent assay, and the 405 nm Absorption value (referenced to the absorption value at 490 nm). After mono-exponential curve fitting, the concentrations at which the polypyridine ruthenium complexes Ru1~Ru4 inhibit half of the HIV reverse transcriptase activity (IC 50 ) were 2.38, 5.42, 5.87, and 8.20 μM, respectively, which were significantly higher than those of aminothiazole compounds without ruthenium complexes. Therefore, the polypyridine ruthenium complex prepared by the invention has high HIV reverse transcriptase inhibitory activity, and is a potential drug for diseases closely related...

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Abstract

The invention belongs to the field of researches and development of acquired immune deficiency syndrome virus inhibitors and discloses a preparation method of a ruthenium complex and acquired immune deficiency syndrome virus reverse transcriptase inhibition application of the ruthenium complex. The invention designs a novel synthesis method of a polypyridine ruthenium complex; the complex has highpurity and high yield and has good water solubility and excellent light spectrum property. The polypyridine ruthenium complex provided by the invention has a capability of selectively combining a TARregion on acquired immune deficiency syndrome virus RNA (Ribonucleic Acid), and can be used for blocking a reverse transcription process of the reverse transcriptase on the virus RNA to inhibit the copying of the virus RNA. The polypyridine ruthenium complex provided by the invention is an acquired immune deficiency syndrome virus RNA selective binding reagent with high affinity and an acquired immune deficiency syndrome virus reverse transcriptase inhibitor with high activity, and is an acquired immune deficiency syndrome virus medicine with extremely good application potential.

Description

technical field [0001] The invention belongs to the field of research and development of HIV reverse transcriptase inhibitors and HIV drugs, and in particular relates to a preparation method of a polypyridine ruthenium complex and its application in HIV reverse transcriptase inhibition. Background technique [0002] AIDS is a disease that seriously endangers human health and life. my country has reported as many as 654,000 HIV-infected persons and patients, with a total of 201,000 deaths. The number of deaths from AIDS is already the first in the number of deaths from infectious diseases in my country. Inhibiting the reverse transcription effect of reverse transcriptase on viral RNA can control the production and spread of the virus, so as to treat and prevent diseases that are temporarily incurable such as AIDS and are closely related to reverse transcriptase and viral RNA effect( science , 1992, 256 , 1783-1790; Biochemistry , 2011, 50 , 5042-5057). Therefore, HIV ...

Claims

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Application Information

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IPC IPC(8): C07F15/00A61P31/18A61K31/555
CPCA61P31/18C07F15/0053
Inventor 高峰闫茹毕徐丹
Owner YUNNAN UNIV
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