SYNTHESIS AND ANTI-HEPATITIS C VIRUS ACTIVITY OF GALLIC ACID DERIVATIVES WITH CHIRAL CENTER

Objective: In this work, we aim to synthesize gallic acid derivatives with chiral center and to evaluate its anti-hepatitis C virus (anti-HCV) activity.Methods: Synthesis of the target derivatives was started from esterification of commercially available boc deprotection (Boc)-L-threonine with allyl bromide, followed by Boc with HCl/EtOAc, amidation, and Sharpless asymmetric dihydroxylation with (DHQ)2PHAL or (DHQD)2PHAL as a ligand to give desired gallic acid derivatives. The synthesized gallic acid derivatives were then evaluated for anti-HCV activity and cytotoxicity.Results: The target derivatives were successfully synthesized in ranging from 20% to 30% of yield. Anti-HCV activity of the derivatives is greatly improved by the presence of chiral center, hydroxyl group, and monomethoxy group on the aromatic ring, with showed no cytotoxicity. This fact revealed that the chiral center, hydroxyl group, and monomethoxy group on the aromatic ring of gallic acid derivatives are responsible for its anti-HCV activity. Moreover, gallic acid derivative which possesses a chiral center of bottom facial stereochemistry was found to have a stronger anti-HCV activity than gallic acid derivative with chiral center of top facial stereochemistry. Suggesting that, bottom facial stereocenter in gallic acid derivative was more effective for anti-HCV activity than the top facial stereocenter.Conclusion: Gallic acid derivatives with chiral center exhibited a greater antiviral activity against HCV than gallic acid. Thus, the derivatives should be considered as a promising candidate for the treatment of HCV infection.

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P420 GALLIC ACID HAS ANTIVIRAL EFFECT AGAINST HEPATITIS C VIRUS (HCV), WHICH IS MEDIATED BY ITS ANTIOXIDANT ACTIVITY

Journal of Hepatology ◽

10.1016/s0168-8278(14)60582-1 ◽

2014 ◽

Vol 60 (1) ◽

pp. S208 ◽

Cited By ~ 3

Author(s):

M. Govea Salas ◽

A.M. Rivas Estilla ◽

J.A. Morlett Chávez ◽

S.A. Lozano Sepúlveda ◽

R. Rodríguez Herrera ◽

...

Keyword(s):

Antioxidant Activity ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Gallic Acid ◽

Antiviral Effect

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Mapping B-Cell Epitopes of Hepatitis C Virus E2 Glycoprotein Using Human Monoclonal Antibodies from Phage Display Libraries

Journal of Virology ◽

10.1128/jvi.75.20.9986-9990.2001 ◽

2001 ◽

Vol 75 (20) ◽

pp. 9986-9990 ◽

Cited By ~ 36

Author(s):

Francesca Bugli ◽

Nicasio Mancini ◽

Chang-Yuil Kang ◽

Cristiana Di Campli ◽

Antonella Grieco ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

B Cell ◽

Promising Candidate ◽

B Cell Epitopes ◽

Reciprocal Interactions ◽

E2 Glycoprotein ◽

Phage Display Libraries ◽

Significant Step ◽

Protective Antibodies

ABSTRACT Clinical and experimental evidence indicates that the hepatitis C virus (HCV) E2 glycoprotein (HCV/E2) is the most promising candidate for the development of an effective anti-HCV vaccine. Identification of the human epitopes that are conserved among isolates and are able to elicit protective antibodies would constitute a significant step forward. This work describes the mapping of the B-cell epitopes present on the surface of HCV/E2, as recognized by the immune system during infection, by the analysis of the reciprocal interactions of a panel of human recombinant Fabs derived from an HCV-infected patient. Three unrelated epitopes recognized by antibodies with no neutralization-of-binding (NOB) activity were identified; a fourth, major epitope was defined as a clustering of minor epitopes recognized by Fabs endowed with strong NOB activity.

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Pyrophosphorolytic Excision of Nonobligate Chain Terminators by Hepatitis C Virus NS5B Polymerase

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00186-07 ◽

2007 ◽

Vol 51 (8) ◽

pp. 2920-2928 ◽

Cited By ~ 29

Author(s):

Jérôme Deval ◽

Megan H. Powdrill ◽

Claudia M. D'Abramo ◽

Luciano Cellai ◽

Matthias Götte

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Rna Synthesis ◽

Hydroxyl Group ◽

Rna Dependent Rna Polymerase ◽

Dead End ◽

Natural Counterpart ◽

Ns5b Polymerase ◽

Classical Chain ◽

Chain Terminators

ABSTRACT Nonobligate chain terminators, such as 2′-C-methylated nucleotides, block RNA synthesis by the RNA-dependent RNA polymerase (RdRp) of hepatitis C virus (HCV). Previous studies with related viral polymerases have shown that classical chain terminators lacking the 3′-hydroxyl group can be excised in the presence of pyrophosphate (PPi), which is detrimental to the inhibitory activity of these compounds. Here we demonstrate that the HCV RdRp enzyme is capable of removing both obligate and clinically relevant nonobligate chain terminators. Pyrimidines are more efficiently excised than are purines. The presence of the next complementary templated nucleotide literally blocks the excision of obligate chain terminators through the formation of a dead-end complex (DEC). However, 2′-C-methylated CMP is still cleaved efficiently under these conditions. These findings show that a 2′-methylated primer terminus impedes nucleotide binding. The S282T mutation, associated with resistance to 2′-C-methylated nucleotides, does not affect the excision patterns. Thus, the decreased susceptibility to 2′-C-methylated nucleotides appears to be based solely on improved discrimination between the inhibitor and its natural counterpart. In conclusion, our data suggest that the phosphorolytic excision of nonobligate, pyrimidine-based chain terminators can diminish their potency. The templated nucleotide does not appear to provide protection from excision through DEC formation.

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Promising Candidate Urinary MicroRNA Biomarkers for the Early Detection of Hepatocellular Carcinoma among High-Risk Hepatitis C Virus Egyptian Patients

Journal of Cancer ◽

10.7150/jca.3.19 ◽

2012 ◽

Vol 3 ◽

pp. 19-31 ◽

Cited By ~ 75

Author(s):

Moemen AK Abdalla ◽

Yousef Haj-Ahmad

Keyword(s):

Hepatocellular Carcinoma ◽

Hepatitis C Virus ◽

Hepatitis C ◽

High Risk ◽

Early Detection ◽

Promising Candidate ◽

Egyptian Patients

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Amidinoanthracyclines – a new group of potential anti-hepatitis C virus compounds

Biological Chemistry ◽

10.1515/bc.2009.040 ◽

2009 ◽

Vol 390 (4) ◽

Cited By ~ 13

Author(s):

Mariusz Krawczyk ◽

Malgorzata Wasowska-Lukawska ◽

Irena Oszczapowicz ◽

Anna M. Boguszewska-Chachulska

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Chemical Structure ◽

Hydroxyl Group ◽

Current Therapy ◽

Helicase Activity ◽

Double Stranded Dna ◽

Helicase Assay ◽

Dna Substrate ◽

Selection Of

Abstract Hepatitis C virus (HCV) infections represent one of the major and still unresolved health problems because current therapy is effective in only 50–80% of cases, depending on viral genotype. A large group of amidinoanthracyclines, with decreased acute toxicity and cardiotoxicity compared to the parent antibiotics, was tested in a high-throughput fluorometric HCV helicase assay. Here, we report the selection of more than 50 potent inhibitors of helicase activity that inhibit the enzyme with IC50 values in the range of 0.03–10 μm; four of these compounds are the most potent inhibitors of helicase activity described in the literature. The activity of these inhibitors is highly dependent on their chemical structure, mainly on the substituent at the amidino carbon atom and on the orientation of the hydroxyl group at the 4′ position of the daunosamine moiety. The most effective compounds act not solely via intercalation into the double-stranded DNA substrate, but also compete with the enzyme for access to the substrate, impeding formation of the active helicase complex. Selected amidinoanthracyclines were tested in the subgenomic HCV replicon system. These experiments confirmed the antiviral activity of two selected inhibitors (EC50 values below 0.2 μm with selectivity indices of 19 and 33) and proved that they may be considered as potential anti-HCV drugs.

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Threonine-Allyl-Ester and Amide of Gallic Acid Derivative as Promising Anti-HCV Inhibitors

Advanced Science Letters ◽

10.1166/asl.2018.12709 ◽

2018 ◽

Vol 24 (8) ◽

pp. 6265-6267

Author(s):

Dadan Ramadhan Apriyanto ◽

Ade Arsianti ◽

Chie Aoki-Utsubo ◽

Fadilah ◽

Anton Bahtiar ◽

...

Keyword(s):

Antiviral Activity ◽

Gallic Acid ◽

Acid Derivative ◽

Allyl Bromide ◽

Effective Concentration ◽

Allyl Ester ◽

Hcv Genotype

In this study, we focused to evaluate threonine-allyl-ester (TAE) and amide of gallic acid derivative (AGA) for anti-HCV activity. The synthesis was started from esterification of commercially available Boc-L-Threonine with allyl bromide, followed by Boc deprotection with HCl/EtOAc produced threonine-allyl-ester (TAE) and amidation of the ester with the gallic acid with WSCD HCl, HOBt, and NMM produced the amide of gallic acid derivative (AGA). The synthesized were examined the antiviral activity against HCV (genotype 2a strain JFH1) and cytotoxicity against Huh7it-1. The synthesized of TAE and AGA were in ranging from 91% to 50% of yield. The TAE and AGA exhibited anti-HCV activity with a 50% effective concentration (EC50) of 24.5 μg/ml and 12.1 μg/ml without cytotoxicity, respectively. These results suggest that TAE and AGA have potential as anti-HCV. Further study, TAE and AGA are synthesized with addition another form.

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Structural requirements of virion-associated cholesterol for infectivity, buoyant density and apolipoprotein association of hepatitis C virus

Journal of General Virology ◽

10.1099/vir.0.032391-0 ◽

2011 ◽

Vol 92 (9) ◽

pp. 2082-2087 ◽

Cited By ~ 19

Author(s):

Mami Yamamoto ◽

Hideki Aizaki ◽

Masayoshi Fukasawa ◽

Tohru Teraoka ◽

Tatsuo Miyamura ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Apolipoprotein E ◽

Molecular Basis ◽

Buoyant Density ◽

Hydroxyl Group ◽

Side Chain ◽

Virus Infectivity ◽

Structural Requirement ◽

Structural Requirements

Our earlier study has demonstrated that hepatitis C virus (HCV)-associated cholesterol plays a key role in virus infectivity. In this study, the structural requirement of sterols for infectivity, buoyant density and apolipoprotein association of HCV was investigated further. We removed cholesterol from virions with methyl β-cyclodextrin, followed by replenishment with 10 exogenous cholesterol analogues. Among the sterols tested, dihydrocholesterol and coprostanol maintained the buoyant density of HCV and its infectivity, and 7-dehydrocholesterol restored the physical appearance of HCV, but suppressed its infectivity. Other sterol variants with a 3β-hydroxyl group or with an aliphatic side chain did not restore density or infectivity. We also provide evidence that virion-associated cholesterol contributes to the interaction between HCV particles and apolipoprotein E. The molecular basis for the effects of different sterols on HCV infectivity is discussed.

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