Application of 1,8-dihexanoyl emodin in preparation of anti-HIV-1 drugs

A technology of dihexanoyl-emodin and emodin, which is applied in the application field of 1,8-dihexanoyl-emodin in the preparation of anti-HIV-1 drugs, and can solve the problems of easy oxidative deterioration, poor stability, and poor solubility of emodin, etc. question

Active Publication Date: 2017-05-31
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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  • Application of 1,8-dihexanoyl emodin in preparation of anti-HIV-1 drugs
  • Application of 1,8-dihexanoyl emodin in preparation of anti-HIV-1 drugs
  • Application of 1,8-dihexanoyl emodin in preparation of anti-HIV-1 drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] [Example 1] Preparation, purification and identification of emodin derivatives

[0041] 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 ).

[0042] 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

[0043] [Example 2] MTT method to detect the cytotoxic effect of emodin derivatives 3-emodin acetate and 1,8-dihexanoyl emodin

[0044]Anticoagulated blood from healthy blood donors was mixed with lymphatic separation fluid (Organon Teknika Corp, Durham), and centrifuged at 1500 g for 45 min 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 monocyte...

Embodiment 3

[0048] [Example 3] Anti-HIV-1 effect of emodin derivatives 3-acetate emodin and 1,8-dihexanoyl emodin in vitro

[0049] 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 Gag mRNA in the cells was detected by RT-PCR; the content of p24 in the supernatant of the cells was detected by ELISA, and the expression of p24 in the cells was measured by Western blotting, and 3-acetate emodin and 1,8-dihexanoyl emodin were determined by the above three aspects Antiviral effects against HIV-1. Specific steps are as follows:

[0050] (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 g...

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Abstract

The invention discloses application of 1,8-dihexanoyl emodin in the preparation of anti-HIV-1 drugs and belongs to the field of antiviral drugs. It is discovered herein that 1,8-dihexanoyl emodin has in-vitro inhibitory action on HIV-1 virus replication, viral inclusions in infected human macrophages are decreased significantly, and no toxic and side effects are caused to human macrophages. The inhibitory action on HIV-1 replication increases with the increase in the concentration of the 1,8-dihexanoyl emodin in vitro, while Gag gene and p24 protein expressions decrease gradually; in addition, the longer the drugs act, the more significant the inhibitory action on HIV-1 infection. The 1,8-dihexanoyl emodin is applicable to the preparation of anti-HIV-1 drugs.

Description

technical field [0001] The present invention is a divisional application for the invention patent application "Emodin Derivatives and Their Application in the Preparation of Anti-HIV-1 Drugs" (Application No.: 2015109749477) submitted on December 21, 2015. 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 ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/222A61P31/18C07C69/30C07C59/125
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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