Emodin derivatives and application thereof in preparation of anti-HIV-1 medicines

An HIV-1, emodin technology, applied in antiviral agents, pharmaceutical formulations, medical preparations containing active ingredients, etc., can solve the problems of poor stability, poor solubility of emodin, easy oxidative deterioration, etc. good water solubility

Active Publication Date: 2016-03-23
WUHAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Emodin belongs to anthraquinone compounds, and the main part of its antiviral effect is anthraquinone, but the solubility of emodin is very poor, almost insoluble in water, only soluble in alkali and some organic solvents such as ethanol, dimethyl sulfoxide ( DMSO), and the stability is relatively poor, easy to oxidize and deteriorate
This has become a major obstacle in the development of clinical application of emodin

Method used

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  • Emodin derivatives and application thereof in preparation of anti-HIV-1 medicines
  • Emodin derivatives and application thereof in preparation of anti-HIV-1 medicines
  • Emodin derivatives and application thereof in preparation of anti-HIV-1 medicines

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0042] [Example 1] Preparation, purification and identification of emodin derivatives

[0043] 3-emodin acetate: take 125mg emodin and 138mg potassium carbonate, add 5mL acetone, and react under reflux at 50°C. After the reaction, add hydrochloric acid to adjust the pH value to 1-2, filter to obtain a red solid, and dry it in a vacuum oven. Add 74.3 mg of the product to a round bottom flask, add 34.7 mg of sodium hydroxide and 15 mL of ethanol, stir at 30 ° C for 4 h, put the reaction solution until no liquid precipitates, dilute with water, adjust the pH value to 1-2 with hydrochloric acid, and extract with ethyl acetate The aqueous phase was combined with the organic phases, dried over sodium sulfate and dried to obtain a red solid, and the nuclear magnetic identification product was 3-acetate emodin ( figure 1 ).

[0044] 1,8-Dihexanoyl-emodin: Dissolve 1g of emodin in a 50mL round-bottomed flask, operate in anhydrous and oxygen-free manner, add 20mL of anhydrous pyridine...

Embodiment 2

[0045] [Example 2] MTT method to detect the cytotoxic effect of emodin derivatives 3-emodin acetate and 1,8-dihexanoyl emodin

[0046]Anticoagulated blood from healthy blood donors was mixed with lymphatic separation solution (OrganonTeknikaCorp, Durham), and centrifuged at 1500g for 45min to separate mononuclear cells. The mononuclear cell layer was collected, suspended with DMEM, and inoculated into 2% gelatin-coated culture dishes, incubated at 37°C for 45 min, and then washed with DMEM to remove unadhered cells. After the adherent cells were digested with EDTA, they were resuspended with complete DMEM (10% FCS, 2 mmol / mL glutamine, 100 U / mL penicillin, 100 μg / mL streptomycin, and non-essential amino acids), and mixed with 10 5 per well in a 96-well plate. After preliminary purification, non-specific esterase staining and fluorescent screening of CD14 monoclonal antibody (Leu-M3) and low-density lipoprotein (LDL) confirmed that 98.5% of the cells in the well were monocytes...

Embodiment 3

[0050] [Example 3] Anti-HIV-1 effect of emodin derivatives 3-acetate emodin and 1,8-dihexanoyl emodin in vitro

[0051] After HIV-1Bal strain infects human macrophages for 2 hours (using RT-PCR and ELISA to determine the establishment of HIV-1 infection), discard the virus liquid, and add 10 μM emodin, 3-acetate emodin or 1 , 8-dihexanoyl-emodin in complete DMEM culture solution, cultivated at 37°C, and collected cells and cell supernatant on the 8th day after infection. The expression of GagmRNA in the cells was detected by RT-PCR; the content of p24 in the cell supernatant was detected by ELISA, and the expression of p24 in the cells was determined by Western blotting. Antiviral effects of HIV-1. Specific steps are as follows:

[0052] (1) Real-time quantitative RT-PCR was used to detect the expression of Gag gene, GAPDH was used as an internal reference, and the control group was treated without adding emodin derivatives. Primers are as follows:

[0053] Gag gene upstre...

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Abstract

The invention discloses application of emodin derivatives 3-acetic emodin and 1,8-dihexanoyl emodin in preparation of anti-HIV-1 medicine, and belongs to the field of anti-virus medicines. 3-acetic emodin and 1,8-dihexanoyl emodin are prepared by means of chemical synthesis, the effect of inhibiting replication of HIV-1 viruses in vitro of 3-acetic emodin and 1,8-dihexanoyl emodin is discovered, the number of virus inclusion bodies in infected human macrophages is remarkably reduced, and the 3-acetic emodin and 1,8-dihexanoyl emodin do not have toxic or side effect on the human macrophages. Along with the increasing concentration of the 3-acetic emodin and 1,8-dihexanoyl emodin, the inhibition effect of the 3-acetic emodin and 1,8-dihexanoyl emodin on replication of HIV-1 in vitro is enhanced, expression of Gag genes and p24 protein is gradually reduced; meanwhile, the longer drugs acts, the more remarkable the effect of inhibiting HIV-1 infection is; and the 3-acetic emodin and 1,8-dihexanoyl emodin can be used for preparing anti-HIV-1 medicines.

Description

technical field [0001] The invention relates to emodin derivatives and their application in the preparation of medicines for treating HIV-1. Background technique [0002] Human immunodeficiency virus (HIV) is the pathogen of AIDS (AIDS). Since the AIDS epidemic, there have been 75 million HIV-infected people in the world, and nearly 750,000 HIV-infected people in my country. In 2014, 104,000 new cases of HIV-infected people and patients were reported, an increase of 14.8% over the previous year. However, currently no region in the world has solved the problem of AIDS treatment, and the number of HIV-infected people will continue to increase. [0003] There are currently more than a dozen anti-HIV drugs approved for the treatment of AIDS. The internationally recognized treatment method is "cocktail" or high-efficiency antiretroviral therapy (that is, 2 reverse transcriptase inhibitors + 1 protease inhibitor), which can significantly reduce the plasma viral load of infected ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C59/13C07C69/30A61K31/192A61K31/222A61P31/18
CPCA61K31/222C07C59/125C07C59/13C07C69/30
Inventor 侯炜王晓昆洪学传程双吴笛笛朱薿李宁陈清宙谢林林罗凡熊海蓉冯勇
Owner WUHAN UNIV
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