Design, Synthesis, and Bioactive Screen In Vitro of Cyclohexyl (E)-4-(Hydroxyimino)-4-Phenylbutanoates and Their Ethers for Anti-Hepatitis B Virus Agents

A series of oxime Cyclohexyl (E)-4-(hydroxyimino)-4-phenylbutanoates and their ethers were designed, synthesized, and evaluated for anti-hepatitis B virus (HBV) activities with HepG 2.2.15 cell line in vitro. Most of these compounds possessed anti-HBV activities, and among them, compound 4B-2 showed significant inhibiting effects on the secretion of HBsAg (IC50 = 63.85 ± 6.26 μM, SI = 13.41) and HBeAg (IC50 = 49.39 ± 4.17 μM, SI = 17.34) comparing to lamivudine (3TC) in HBsAg (IC50 = 234.2 ± 17.17 μM, SI = 2.2) and HBeAg (IC50 = 249.9 ± 21.51 μM, SI = 2.07). Docking study of these compounds binding to a protein residue (PDB ID: 3OX8) from HLA-A2 that with the immunodominant HBcAg18–27 epitope (HLA-A2.1- restricted CTL epitope) active site was carried out by using molecular operation environment (MOE) software. Docking results showed that behaviors of these compounds binding to the active site in HLA-A protein residue partly coincided with their behaviors in vitro anti-HBV active screening.

Download Full-text

Production of hepatitis B virus in vitro by transient expression of cloned HBV DNA in a hepatoma cell line.

The EMBO Journal ◽

10.1002/j.1460-2075.1987.tb04807.x ◽

1987 ◽

Vol 6 (3) ◽

pp. 675-680 ◽

Cited By ~ 112

Author(s):

C.M. Chang ◽

K.S. Jeng ◽

C.P. Hu ◽

S.J. Lo ◽

T.S. Su ◽

...

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Cell Line ◽

Transient Expression ◽

Hepatoma Cell ◽

Hbv Dna ◽

Hepatoma Cell Line ◽

B Virus

Download Full-text

Over IFI16 expression increased inflammation in Hepatitis B Virus-Associated Glomerulonephritis by Regulating Caspase-1 and IL-1 ß

10.21203/rs.3.rs-15455/v1 ◽

2020 ◽

Author(s):

zhaoqing zeng ◽

yuyang li ◽

jinhong yu ◽

jing liu ◽

shijun chen ◽

...

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Cell Line ◽

Renal Damage ◽

Hbv Infection ◽

Inflammatory Factors ◽

Inflammasome Activation ◽

Caspase 1 ◽

B Virus

Abstract Aims & background: IFI16 plays an important role in innate immunity against invasive microbial infection by sensing double-stranded DNA viruses due to caspase-1-dependent inflammasome activation and subsequent maturation and secretion of IL-1β. However, the role of IFI16 in regulating the immune response to viruses in vivo and in vitro, especially in sensing hepatitis B virus (HBV), has not been examined. We hypothesized that the expression of IFI16 increases corresponding to HBV-mediated inflammation in patients with hepatitis B virus associated glomerulonephritis (HBV-GN), a condition which activates inflammatory mechanisms and causes renal damage. To test this hypothesis, we therefore analyzed the expression of IFI16 and inflammatory factors in HBV-GN tissues and cell lines relative to the inflammatory response to HBV infection. Methods: A total 75 patients with chronic nephritis(CN) including 50 with HBV-GN and 25 with chronic glomerulonephritis (CCN) involved in this study. Each CN patient received renal biopsy, and immunohistochemistry(IHC) was used to detect the expression of IFI16 and inflammatory factors Caspase-1 and IL-1β in the biopsy specimens. Following IFI16 was transfected in HBV-infected and HBV-uninfected human glomerular mesangial (HGM) cell line and HEK-293T cell line, expression of Caspase-1 and IL-1β were detected by Western blot and qRT- PCR. Results: IFI16 expression in HBV-GN biopsies (80.0%) was significantly higher than in CGN (24.0%) and positively correlated with caspase-1 and IL-1𝛽 expression in HBV-GN. In vitro, over expression IFI16 increased caspase-1 and IL-1𝛽 expression in HBV -infected HGM and HEK-293T. Conclusions: The elevation of IFI16 during HBV infection or replication may contribute to renal damage due to inflammation, thus providing a putative therapeutic target and a new avenue for researching the pathogenesis of HBV-GN.

Download Full-text

Effect of hepatitis B virus infection on apoptosis of a human choriocarcinoma cell line in vitro

Journal of Obstetrics and Gynaecology Research ◽

10.1111/jog.12046 ◽

2013 ◽

Vol 39 (6) ◽

pp. 1200-1211 ◽

Cited By ~ 3

Author(s):

Guiqin Bai ◽

Fengping Fu ◽

Yao Tang ◽

Yueling Wang

Keyword(s):

Hepatitis B Virus ◽

Virus Infection ◽

Hepatitis B ◽

Cell Line ◽

Hepatitis B Virus Infection ◽

B Virus ◽

Choriocarcinoma Cell Line

Download Full-text

IFI16 induces inflammation in Hepatitis B Virus-Associated Glomerulonephritis by Regulating the Caspase-1 /IL-1ß pathway

10.21203/rs.3.rs-687220/v1 ◽

2021 ◽

Author(s):

Li Liu ◽

Xiuhua Zhao ◽

Shuangshuang Xie ◽

Cheng Li ◽

Yue Guo ◽

...

Keyword(s):

Immune Response ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Cell Line ◽

293T Cell ◽

Hbv Infection ◽

Caspase 1 ◽

B Virus

Abstract Aims & backgroundIFI16 plays an important role in innate immunity against invasive microbial infection by sensing double-stranded DNA viruses due to caspase-1-dependent inflammasome activation and subsequent maturation and secretion of IL-1β. However, the role of IFI16 in regulating the immune response to viruses in Hepatitis B Virus-Associated Glomerulonephritis(HBV-GN), especially in sensing the hepatitis B virus (HBV), has not been determined. In this study,, we investigated the inflammatory role of IFI16 in HBV-GN.MethodsA total of 75 kidney tissues including 50 HBV-GN and 25 chronic glomerulonephritis (CCN) were collected to determine expression of IFI16, Caspase-1, and IL-1𝛽 by immunohistochemistry (IHC), and then the correlation between them was analyzed. In vitro, the overexpression or knockdown of IFI16 in regulating the immune response to HBV infection in the human glomerular mesangial (HGM) cell line and HEK-293T cell line. Quantitative Real-time PCR and western blotting were used to determine the expression of IFI16, Caspase-1 and IL-1β. The role effect of IFI16 in vivo was further investigated.ResultsIFI16 expression in HBV-GN biopsies (80.0%) was significantly higher than in CGN (24.0%) and was positively correlated with caspase-1 and IL-1𝛽 expression in HBV-GN. In vitro, over expression of IFI16 increased caspase-1 and IL-1𝛽 expression in HBV-infected HGM and HEK-293T cell lines, whereas knockdown of IFI16 mRNA by siRNA resulted in downregulation of the caspase-1 and IL-1𝛽 expression in both cell lines.ConclusionsThe elevation of IFI16 during HBV infection or replication may contribute to renal damage due to inflammation, thus providing a putative therapeutic target and a new avenue for studying the pathogenesis of HBV-GN.

Download Full-text

Identification of BMS-200475 as a potent and selective inhibitor of hepatitis B virus.

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.41.7.1444 ◽

1997 ◽

Vol 41 (7) ◽

pp. 1444-1448 ◽

Cited By ~ 209

Author(s):

S F Innaimo ◽

M Seifer ◽

G S Bisacchi ◽

D N Standring ◽

R Zahler ◽

...

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Cell Line ◽

Nucleoside Analogs ◽

Hbv Replication ◽

Mitochondrial Dna Content ◽

B Virus ◽

Antiviral Activities ◽

Replicative Intermediates

BMS-200475 is a novel carbocyclic 2'-deoxyguanosine analog found to possess potent and selective anti-hepatitis B virus (anti-HBV) activity. BMS-200475 is distinguished from guanosine by replacement of the natural furanose oxygen on the sugar moiety with an exo carbon-carbon double bond. In the HepG2 stably transfected cell line 2.2.15, BMS-200475 had a 50% effective concentration (EC50) of 3.75 nM against HBV, as determined by analysis of secreted HBV DNA. Structurally related compounds with adenine, iodouracil, or thymine base substitutions were significantly less potent or were inactive. Direct comparison of the antiviral activities of BMS-200475 with those of a variety of other nucleoside analogs, including lamivudine (EC50 = 116.26 nM), demonstrated the clearly superior in vitro potency of BMS-200475 in 2.2.15 cells. Intracellular HBV replicative intermediates were uniformly reduced when cells were treated with BMS-200475, but rebounded after treatment was terminated. The concentration of BMS-200475 causing 50% cytotoxicity in 2.2.15 cell cultures was 30 microM, approximately 8,000-fold greater than the concentration required to inhibit HBV replication in the same cell line. Treatment with BMS-200475 resulted in no apparent inhibitory effects on mitochondrial DNA content.

Download Full-text