Application of bergapten in preparation of HIV-1 latent infection reversal agent

Abstract

The invention discloses an application of bergapten in preparation of an HIV-1 latent infection reversal agent. According to the research by the inventor of the invention, the bergapten is found to have the capacity of activating an HIV-1 latent infection cell model in vitro and not to show obvious cytotoxicity at 400 [mu]M. Different from obvious increase of CD25 and CD69 expression quantities caused by a positive control drug, namely Prostratin, the expression quantities of CD25 and CD69 in human peripheral blood cells treated by the bergapten are not obviously changed, and no side effects of T cell activation is caused. The bergapten is expected to provide a new way and means for induced activation and final elimination of HIV latent infection viruses.

Description

technical field [0001] The present invention relates to a new application of compounds, in particular to the application of bergapten (Bergapten, 5-Methoxypsoralen) as HIV-1 latent infection reversing agent or activator. Background technique [0002] AIDS (acquired immune deficiency syndrome, AIDS) is caused by human immunodeficiency virus (human immunodeficiency virus, HIV), the most serious single-cause disease in humans, and its main feature is that it can cause serious damage to the systemic immune system. As of 2017, the number of people infected with HIV worldwide has reached 36.9 million, and 90 million people have died of AIDS, which seriously threatens human health and survival. According to the latest data in 2017, the number of HIV carriers in China has exceeded 700,000, and the infection rate among young men is increasing year by year. In 1996, the combination of three or more antiretroviral drugs was used to treat AIDS—Highly active antiretroviral therapy (HAAR...

AI Technical Summary

Problems solved by technology

[0019] However, the above-mentioned candidate LRAs for the treatment of HIV latent infection are still only in the clinical trial stage, and breakthrough progress has not yet been made. They have more or less certain defects, which limit their wide application in clinical practice.

The main issues are as follows: 1) Some epigenetic therapy drugs can also cause many side effects while activating the virus. For example, the mechanism of HDAC inhibitors is controversial, and nausea, vomiting, and blood system abnormalities have also been reported in clinical practice. and affect the normal function of genes; 2) PKC activators can affect the transcription factor signaling pathway of normal T cell activation, thereby complicating the body's immunity and chemical drug clearance of HIV latent virus reservoirs, and theoretically may also lead to endogenous reverse transcription Activation of enzyme viruses or activation of DNA viruses, including cytomegalovirus (Cytomegaoviyns, CMV), hepatitis B virus (Hepatitis B virus, HBV) and JC virus, etc.

3) Some drugs have poor specificity, wide range of effects, large toxic and side effects, and are not suitable for long-term application, etc.

4) Some candidate LRAs drugs have been proved to have a good effect on activating latent viruses in in vitro cell experiments, but the clinical research results are not very satisfactory

Lee T T Y, Kashiwada Y, Huang L, et al. Results (Lee T T Y, Kashiwada Y, Huang L, et al. Suksdorfin: An anti-HIV principle from Lomatiumsuksdorfii, its structure-activity correlation with related coumarins, and synergistic effects with anti- AIDS nucleosides[J].Bioorganic&medicinal chemistry,1994,2(10):1051-1056.) shows that bergamotide has a weak inhibitory effect on HIV-1 replication, and its IC 50 The value is 208.3 μM, EC 50 The value is 30.1μM, the therapeutic index is 6.9, basically invalid

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