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Application of benzo Alpha-pyrone compound as Gamma-type human herpes virus-resistant medicine

A human herpes virus and compound technology, applied in the treatment of diseases related to γ-type human herpes virus infection, in the field of benzo α-pyrone compounds, can solve the problems of lack of cleavage and replication, and achieve high incidence of KS, Easy to synthesize and reduce the incidence of disease

Active Publication Date: 2014-09-17
SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Studies have confirmed that KSHV cannot establish a stable latent infection in the host without lytic replication (Grundhoff and Ganem, 2004.J.Clin.Invest.113:124-136)

Method used

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  • Application of benzo Alpha-pyrone compound as Gamma-type human herpes virus-resistant medicine
  • Application of benzo Alpha-pyrone compound as Gamma-type human herpes virus-resistant medicine
  • Application of benzo Alpha-pyrone compound as Gamma-type human herpes virus-resistant medicine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0042] Example 1: Virtual screening of compounds

[0043] 1. Compound library preprocessing: The virtual screening compound library is a self-prepared compound database. The compound library is processed as follows: removing ions and complexing water molecules, adding charges, protonating, and generating three-dimensional conformations. These processes are completed in the drug design software package Discovery Studio2.5. The protonation is carried out at pH6.5-8.5. Prepare small molecule libraries for virtual screening.

[0044] 2. Search the database for substructure matching based on the benzoα-pyrone structure to find compounds containing the parent nucleus. Finally, 7 compounds (C18, C19, C28, C30, C33, C34, C35) were selected for cytological experiments. The chemical structures of the compounds are shown in Table 1.

Embodiment 2

[0045] Example 2: Determination of KSHV split replication inhibitory activity

[0046] 1. Cell culture. BCBL-1 cells (primary effusion lymphoma cell line, containing latent KSHV) were cultured in vitro. The RPMI1640 medium containing 10% fetal bovine serum was used for routine maintenance and passage at 37°C and 5% carbon dioxide concentration.

[0047] 2. Drug intervention. Adjust the logarithmic growth phase BCBL-1 cell density to 3×10 5 cells / ml, use 20ng / ml Tetradecanoyl phorbol acetate (TPA) to induce BCBL-1 cells to enter the lytic replication phase. The compounds to be tested were formulated as drug solutions with different concentrations using DMSO. After BCBL-1 cells were treated with TPA for 3 hours, the cells were treated with different concentrations of compounds (the above 7 compounds), and three parallel wells were set up for each concentration, and a control group without TPA induction and without compound treatment was set up Compare.

[0048] 3. Test met...

Embodiment 3

[0052] Example 3 Inhibition of KSHV Virus Particle Release Experiment

[0053] 1. Cell culture. BCBL-1 cells were cultured in vitro. Use RPMI1640 medium containing 10% fetal bovine serum, 100 U / ml penicillin, and 100 μg / ml streptomycin for routine maintenance and passage at 37°C and 5% carbon dioxide concentration.

[0054] 2. Drug intervention. Adjust the logarithmic growth phase BCBL-1 cell density to 3×10 5 cells / ml, use 20ng / ml TPA to induce BCBL-1 cells to enter the lytic replication phase. The compounds to be tested were prepared in different concentrations using DMSO. After BCBL-1 cells were treated with TPA for 3 hours, the cells were treated with different concentrations of compounds (the above 7 compounds), and three parallel wells were set up for each concentration, and a control group without compound treatment and without TPA induction was set up Compare.

[0055] 3. Test method. After the cells were treated with TPA for 5 days, the cell culture solution wa...

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Abstract

The invention discloses an application of a benzo Alpha-pyrone compound as a Gamma-type human herpes virus-resistant medicine. According to the invention, the compound resistant to Gamma-type human herpes virus infection is higher in activity as compared with a novobiocin which is a marketed medicine, and is less in toxicity based on a cytoxicity test. The compound can be used for curing or preventing related diseases caused by KSHV infection.

Description

technical field [0001] The invention belongs to the field of biopharmaceuticals, and specifically relates to a class of benzo-α-pyrone compounds, including such compounds and compositions thereof, and the application of the compounds and compositions in the treatment of diseases related to gamma-type human herpesvirus infection , the γ-type human herpesvirus mainly refers to Kaposi's sarcoma-associated herpesvirus and Epstein-Barr virus. technical background [0002] Kaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus type 8 (HHV-8), belongs to the γ-type human herpesvirus. KSHV was first discovered in the sarcoma tissue of Kaposi's sarcoma (Kaposi's sarcoma, KS) patient by the pathologist Chang et al. of Columbia University in 1994 by means of representative difference analysis. Epidemiological studies have confirmed that KSHV infection is the pathogenic factor of many malignant diseases, among which the incidence of Kaposi's sarcoma and primary...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/37A61K31/365A61K31/7048A61P31/22
Inventor 袁岩徐峻
Owner SUN YAT SEN UNIV
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