Approximately 71 million people suffer from hepatitis C virus (HCV) infection worldwide. Persistent HCV infection causes liver diseases such as chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma, resulting in approximately 400,000 deaths annually. Effective direct-acting antiviral agents (DAAs) have been developed and are currently used for HCV treatment targeting the following three proteins: NS3/4A proteinase that cleaves the HCV polyprotein into various functional proteins, RNA-dependent RNA polymerase (designated as NS5B), and NS5A, which is required for the formation of double membrane vesicles serving as RNA replication organelles. At least one compound inhibiting NS5A is included in current HCV treatment regimens due to the high efficacy and low toxicity of drugs targeting NS5A. Here we report fluorene compounds showing strong inhibitory effects on GT 1b and 3a of HCV. Moreover, some compounds were effective against resistance-associated variants to DAAs. The structure-activity relationships of the compounds were analyzed. Furthermore, we investigated the molecular bases of the inhibitory activities of some compounds by the molecular docking method.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.antiviral.2019.104678 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The Role of Torsion on the Force-Coupled Reactivity of a Fluorenyl Naphthopyran Mechanophore.
J Am Chem Soc
January 2025
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, United States.
The unique reactivity of molecules under force commands an understanding of structure-mechanochemical activity relationships. While conceptual frameworks for understanding force transduction in many systems are established, systematic investigations into force-coupled molecular torsions are limited. Here, we describe a novel fluorenyl naphthopyran mechanophore for which mechanical force is uniquely coupled to the torsional motions associated with the overall chemical transformation as a result of the conformational rigidity imposed by the fluorene group.
View Article and Find Full Text PDFBioactive Sulfonamides Derived from Amino Acids: Their Synthesis and Pharmacological Activities.
Mini Rev Med Chem
January 2025
Department of Physiology and Pharmacology Vittorio Erspamer, Sapienza University of Rome, 00161, Rome, Italy.
Currently, the synthesis of bioactive sulfonamides using amino acid as a starting reagent has become an area of research interest in organic chemistry. Over the years, an amine-sulfonyl chloride reaction has been adopted as a common step in traditional sulfonamide synthetic methods. However, recent developments have shown amino acids to be better precursors than amines in the synthesis of sulfonamides.
View Article and Find Full Text PDFDiscovery of Triketone-Indazolones as Novel 4-Hydroxyphenylpyruvate Dioxygenase Inhibiting-Based Herbicides.
J Agric Food Chem
January 2025
State Key Laboratory of Green Pesticide, International Joint Research Center for Intelligent Biosensor Technology and Health, Central China Normal University, Wuhan 430079, PR China.
4-Hydroxyphenylpyruvate dioxygenase (HPPD) is a crucial herbicide target in current research, playing an important role in the comprehensive management of resistant weeds. However, the limited crop selectivity and less effectiveness against grass weeds of many existing HPPD inhibitors, limit their further application. To address these issues, a series of novel HPPD inhibitors with fused ring structures were designed and synthesized by introducing an electron-rich indazolone ring and combining it with the classical triketone pharmacophore structure.
View Article and Find Full Text PDFReview on antibacterial flavonoids from genus : Structure-activity relationship and mode of action.
Heliyon
January 2025
Department of Chemical Sciences, Faculty of Science and Technology, Universiti Kebangsaan Malaysia (UKM), 46300, Bangi, Selangor, Malaysia.
The Fabaceae family, particularly genus , is renowned for significant medicinal properties. These plants have been used as natural remedies to address various health issues and are rich in flavonoids. Therefore, this review aimed to provide a comprehensive overview of antibacterial activity, structure-activity relationship, especially against drug-resistance and mode of action for flavonoids isolated from .
View Article and Find Full Text PDFTowards targeted cancer therapy: Synthesis, characterization, and biological activity of a new Cu(II)-ibuprofen-2,2'-dipyridylamine metal complex.
Heliyon
January 2025
Department of Chemistry and CICECO-Aveiro Institute of Materials, University of Aveiro, 3810-193, Aveiro, Portugal.
This work reports the synthesis of a copper metal complex with the nonsteroidal anti-inflammatory drug (NSAID) ibuprofen, and 2,2'-dipyridylamine employing microwave-assisted synthesis (MWAS). To the best of authors knowledge, this is the first study reporting a NSAID-based complex achieved through MWAS. The coordination compound was characterised by elemental analysis, Fourier transform infrared spectroscopy, thermogravimetry, and ultraviolet-visible spectrophotometry.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!