Corrigendum: Exploration of acetanilide derivatives of 1-(ω-phenoxyalkyl)uracils as novel inhibitors of Hepatitis C Virus replication

نویسندگان

  • Andrea Magri
  • Alexander A. Ozerov
  • Vera L. Tunitskaya
  • Vladimir T. Valuev-Elliston
  • Ahmed Wahid
  • Mario Pirisi
  • Peter Simmonds
  • Alexander V. Ivanov
  • Mikhail S. Novikov
  • Arvind H. Patel
چکیده

Hepatitis C Virus (HCV) is a major public health problem worldwide. While highly efficacious directly-acting antiviral agents have been developed in recent years, their high costs and relative inaccessibility make their use limited. Here, we describe new 1-(ω-phenoxyalkyl)uracils bearing acetanilide fragment in 3 position of pyrimidine ring as potential antiviral drugs against HCV. Using a combination of various biochemical assays and in vitro virus infection and replication models, we show that our compounds are able to significantly reduce viral genomic replication, independently of virus genotype, with their IC50 values in the nanomolar range. We also demonstrate that our compounds can block de novo RNA synthesis and that effect is dependent on a chemical structure of the compounds. A detailed structure-activity relationship revealed that the most active compounds were the N(3)-substituted uracil derivatives containing 6-(4-bromophenoxy)hexyl or 8-(4-bromophenoxy)octyl fragment at N(1) position.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Comparison of PEG Interferon Loaded and non-Loaded Iron Oxide Nanoparticles on Hepatitis C Virus Replication in Cell Culture System

Background and Aims: Iron oxide nanoparticles are among the most effective tools which can replace current medical techniques for diagnosis and treatment of various diseases. Hepatitis C infection is one of the main health problems in the world, affecting around 3% of the world's population. This infection can develop into liver cirrhosis and liver cancer over the time in 80% of patients. In t...

متن کامل

Design, Synthesis, Molecular Modeling Studies and Biological Evaluation of N'-Arylidene-6-(benzyloxy)-4-oxo-1,4-dihydroquinoline-3-carbohydrazide Derivatives as Novel Anti-HCV Agents

HCV-induced hepatitis is one of the most debilitating diseases. The limited number of anti-HCV drugs and drug-resistance necessitate developing of new scaffolds with different mode of actions. HCV non-structural protein 5B (NS5B) is an attractive target for development of novel inhibitors of HCV replication. In this paper, new N'-arylidene-6-(benzyloxy)-4-oxo-1,4-dihydroquinoline-3-carbohydrazi...

متن کامل

Design, Synthesis, Molecular Modeling Studies and Biological Evaluation of N'-Arylidene-6-(benzyloxy)-4-oxo-1,4-dihydroquinoline-3-carbohydrazide Derivatives as Novel Anti-HCV Agents

HCV-induced hepatitis is one of the most debilitating diseases. The limited number of anti-HCV drugs and drug-resistance necessitate developing of new scaffolds with different mode of actions. HCV non-structural protein 5B (NS5B) is an attractive target for development of novel inhibitors of HCV replication. In this paper, new N'-arylidene-6-(benzyloxy)-4-oxo-1,4-dihydroquinoline-3-carbohydrazi...

متن کامل

Antiviral Profile of Brown and Red Seaweed Polysaccharides Against Hepatitis C Virus

Hepatitis C virus (HCV) has infected 3% of the population worldwide and 20% of the population in Egypt. HCV infection can lead to hepatocellular carcinoma and death. The presently available treatment with interferon plus ribavirin, has limited benefits due to adverse side effects. Seaweeds have become a major source of new compounds to treat viral diseases. This work aimed to study the effect o...

متن کامل

A Novel Multi-Epitope Vaccine For Cross Protection Against Hepatitis C Virus (HCV): An Immunoinformatics Approach

Background: Hepatitis C virus (HCV) causes acute and chronic human hepatitis infections. Due to the high genetic diversity and high rates of mutations in the genetic material so far there is no approved vaccine against HCV. Materials and Methods: The aim of this study was to determination B and T cell conserved epitopes of E1 and E2 proteins from HCV and construction of a chimeric pepti...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 6  شماره 

صفحات  -

تاریخ انتشار 2016