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Inhibitory Effect of Polyoxometalates on Hepatitis B Virus in Vitro

Author: WangJuan
Tutor: LiJuan
School: Jilin University
Course: Occupational and Environmental Health
Keywords: Hepatitis B virus Polyoxometalates synthesis characterization activity
CLC: R512.62
Type: Master's thesis
Year: 2011
Downloads: 41
Quote: 0
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Abstract


Chronic Hepatitis B (Chronic Hepatitis B, CHB) is a global spread of the disease, with a contagious, transmission complex and broad popularity, the incidence rate and so on. The disease is caused by the hepatitis B virus (Hepatitis B virus, HBV) infections. HBV replication in the body can cause sustained varying degrees of liver inflammation, some patients may develop cirrhosis, hepatocellular carcinoma or liver function Failure. HBV infection is a tremendous’ global threat to public health, according to WHO statistics, the world’s top 10 ranking in the death cause disease, hepatitis B ranked No.7. Therefore, the treatment of hepatitis B has become an urgent major public health problem.Persistent infection with the virus and cause immune dysfunction is the main mechanism of hepatitis B disease.It becomes clear the hepatitis B virus in the main method of treatment. The current anti-HBV drugs mainly include two categories, namely, immunomodulatory agents (interferon and thymosin. etc.) and viral inhibitors (adefovir dipivoxil and lamivudine, etc.). However, these drugs in use have different degrees of drug resistance and greater side effects.Drug concentration in the liver is less difficult to completely remove the virus in liver cells. Therefore, the development of efficient, cheap and safe anti-HBV drugs is of great significance.The subject use of inorganic method self-designed and synthesized a series of new rare earth compound. Using Fourier transform infrared spectroscopy. UV-visible spectroscopy. and X-ray diffraction, the structure of the compounds were characterized.By cell Biology, molecular biology experiments, a series of compounds were detected cytotoxic activity against HBV in vitro. In the experimental study.using Hep G2.2.15 cells as a model to detect the inhibition extracellular secretion of HBeAg and HbsAgof number of tested compounds 1.2.3 and the secretion of extracellular DNA inhibition. Toxicological evaluation of new drugs in accordance with methods of calculation of therapeutic index of compounds on the in vitro anti-HBV activity of compounds, a comprehensive evaluation. 1 Synthesis and characterization of compounds The study use of inorganic method, self-designed and synthesized a series of rare earth heteropoly compounds. Good water solubility of these compounds, high thermal stability, pH range of stabilization. IR spectra of the compounds in the 700～1100cm-1 range are four major peaks, this is the Keggin structure characteristic absorption peak; UV-visible spectra in the vicinity of 200nm and 260nm are two absorption peaks, they are the Od→W and Ob, c→W charge transfer transition generated. In summary, the common description of the two methods are synthesized to maintain the parent compound structure.2 Anti-HBV activity in vitro.In this study, three kinds of structure optimization of novel, stable compounds, in order to HepG 2 2.2.15 cell model compounds by MTT cytotoxicity assay, the results show that the tested compounds No.1.2.3 on Hep G2 2.2.15 cell half of the toxic concentration (24h CC50) were 922.57μg/mL,3104.56μg/mL.1327.39μg/mL. According to results of experiments in vitro cytotoxicity of anti-HBV compounds used in the experiment the highest concentration is 180μg/mL. Tested by ELISA assay of three compounds on the cell culture supernatant inhibited HBsAg and HBeAg content, the results showed that with increasing concentrations of the three tested compounds inhibited the secretion of HBeAg and HBsAg gradually increased. Compound 2 has the strongest inhibition. EC50 values were 37.91μg/mL and 61.67μg/mL. HBeAg. HBsAg content of positive control group ADV has no significant impact. The experimental group compared with the negative control group were statistically significant (P<0.05). Comparison of antigen overall therapeutic index (TI), TI values of the three compounds tested were significantly higher than the positive control drug ADV.Detected by fluorescence quantitative PCR tested compounds No.1,2,3 on extracellular HBV DNA content, the results showed that with concentration, tested compounds on the inhibition of extracellular HBV DNA increased.Concentration and inhibition rate of compound has relationship between the dose-dependent. ADV on extracellular HBV DNA of TI is 35.23. tested compounds No.1.2,3 of TI respectively 25.40,91.63.25.88.Therefore. the 3 compounds on the inhibition of HBV DNA was significantly better than the positive control drug. In summary, this study synthesized rare earth compound with good activity against HBV. For the HPC in the hepatitis virus opens up a new era. but also for the development of non-nucleoside anti-HBV drugs laid the foundation.

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CLC: > Medicine, health > Internal Medicine > Infectious disease > Viral infections > Viral Hepatitis > Hepatitis B
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