Application of 4-dimethyl amino nitrogen-5-hydroxy-formyl-hexyl amine for preparing anti-human immunodeficiency virus (HIV) latent medicine

A kind of technology of dimethylamino nitrogen and hexylamine, applied in the field of medicine

Inactive Publication Date: 2011-04-06
FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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  • Application of 4-dimethyl amino nitrogen-5-hydroxy-formyl-hexyl amine for preparing anti-human immunodeficiency virus (HIV) latent medicine
  • Application of 4-dimethyl amino nitrogen-5-hydroxy-formyl-hexyl amine for preparing anti-human immunodeficiency virus (HIV) latent medicine
  • Application of 4-dimethyl amino nitrogen-5-hydroxy-formyl-hexyl amine for preparing anti-human immunodeficiency virus (HIV) latent medicine

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Experimental program
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Effect test

Embodiment 1

[0054] The effect concentration of embodiment 1.M344 compound is on the influence of HIV latent induction activation efficiency

[0055] A7 cells were planted in a 96-well plate at 2×10E4 cells per well, and 100 ul of 1640 medium (Gibco) containing 10% FBS (Gibco) was added to each well. After 24 hours, different concentrations of M344 were added so that the final concentrations were 0nM, 25nM, 50nM, 100nM, 200nM, 400nM. At least 3 replicate wells for each concentration, and each experiment was repeated 3 times. After the cells were treated with drugs for 72 hours, the expression of GFP in the cells was observed under a fluorescence microscope, and the cells were collected for flow cytometry detection to analyze the proportion of fluorescent cells. Treat the cells with the same concentration of the same positive control drug TSA, analyze and compare the induction and activation rate.

[0056] The results showed that with the increase of M344 compound concentration, the numbe...

Embodiment 2

[0057] Effect of the action time of the embodiment 2.M344 compound on the efficiency of HIV latency induction and activation

[0058] 2×10E4 A7 cells per well were planted in a 96-well plate, and 100 ul of 1640 medium (Gibco) containing 10% FBS (Gibco) was added to each well. After 24 hours, M344 or TSA was added at a final concentration of 100 nM. After 24h, 48h, 72h, and 96h of drug-treated cells, the expression of GFP in the cells was observed under a fluorescent microscope, and the cells were collected for flow cytometry detection to analyze the proportion of fluorescent cells. There were at least 3 replicate wells at each time point, and each experiment was repeated 3 times. Analyze and compare the kinetic characteristics of induced activation induced activation.

[0059] The results showed that when 100nM concentrations of M344 and TSA treated HIV latent infection cell models respectively, one day later, the number of green fluorescent positive cells gradually increase...

Embodiment 3

[0060] Example 3. Toxic effect of M344 on cells

[0061] 2×10E4 normal human embryonic kidney cells (293HEK) were planted in a 96-well plate per well, and 100 ul of DMEM medium (Gibco) containing 10% FBS (Gibco) was added to each well. After 24 hours, different concentrations of M344 and TSA were added so that the final concentrations were 0nM, 25nM, 50nM, 100nM, 200nM, 400nM. At least 3 replicate wells for each concentration, and each experiment was repeated 3 times. After the cells were treated with drugs for 72 hours, MTT reagent (0.5 mg / mL) (purchased from SIGMA) was added to each well, shaken for 1 hour, and the OD value was measured at 570 nm on a microplate reader. Calculate CC50=(OD value of experimental group / OD value of control group)×100%.

[0062] The results showed that the median toxic concentration of M344 drug to normal human cells was CC50=352nM; the median toxic concentration of TSA drug to cells was CC50=170nM; the higher the CC50, the lower the cytotoxici...

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Abstract

The invention belongs to the medical field and relates to an application of 4-dimethyl amino nitrogen-5-hydroxy-formyl-hexyl amine for preparing an anti-human immunodeficiency virus (HIV) latent medicine. The compound has the effect on inducing activation of HIV latent cells, and the compound can be added into a cell culture fluid to induce activation of the HIV latent cells. The compound can be combined with a methyltransferase inhibitor or cell factors or an NF-kB signal activator to form an anti-HIV medicine composition; and the compound can also be combined with the existing HIV medicines to better inhibit and eliminate HIV viruses. Compared with the similar compounds, the compound of the invention has better effect on inducing activation of the HIV latent cells and lower cell toxicity. Especially, the compound can be combined with antiretroviral agents to kill the activated cells of latent infection, thereby accelerating the elimination of a latent virus reservoir. The invention provides a new method and way for thoroughly curing the acquired immune deficiency syndrome (AIDS).

Description

technical field [0001] The invention belongs to the field of medicine, and relates to the application of a compound 4-dimethylaminonitrogen-5-hydroxy-formyl-hexylamine in the preparation of anti-HIV latent drugs. Background technique [0002] Acquired Immunodeficiency Syndrome (AIDS) is an infectious disease caused by HIV infection that seriously endangers people's life and health. According to WHO statistics, there are more than 40 million AIDS patients in the world, with 5 million new patients and 3 million deaths each year. At present, the clinical treatment of AIDS is mainly Highly active antiretroviral therapy (HAART), because it can effectively reduce the viral load (virus load) and protect the immune function, thus prolonging the life expectancy of HIV-infected patients accordingly. survival time. However, this therapy can only inhibit virus replication, and cannot completely eliminate HIV infection. Most patients will experience viral rebound after interrupting HAA...

Claims

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Application Information

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IPC IPC(8): A61K31/16A61P31/18C12N5/0786C12N5/0783C12N5/0784C12N5/0787C12N5/0793C12N5/079C12N5/071
Inventor 朱焕章英昊
Owner FUDAN UNIV
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