High-Throughput Screening, Discovery, and Optimization To Develop a Benzofuran Class of Hepatitis C Virus Inhibitors.
Shanshan He,Prashi Jain,Billy Lin,Marc Ferrer,Zongyi Hu,Noel Southall,Xin Hu,Wei Zheng,Benjamin Neuenswander,Chul Hee Cho,Yu Chen,Shilpa A. Worlikar,Jeffrey Aubé,Richard C. Larock,Frank J. Schoenen,Juan J. Marugan,T. Jake Liang,Kevin J. Frankowski +17 more
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The optimization of the benzofuran scaffold led to the identification of several exemplars with potent inhibition of HCV, low cytotoxicity, and excellent selectivity, and the design and synthesis of a 45-compound library to comprehensively explore the anti-HCV activity.Abstract:
Using a high-throughput, cell-based HCV luciferase reporter assay to screen a diverse small-molecule compound collection (∼ 300,000 compounds), we identified a benzofuran compound class of HCV inhibitors The optimization of the benzofuran scaffold led to the identification of several exemplars with potent inhibition (EC50 25 μM), and excellent selectivity (selective index = CC50/EC50, > 371-fold) The structure-activity studies culminated in the design and synthesis of a 45-compound library to comprehensively explore the anti-HCV activity The identification, design, synthesis, and biological characterization for this benzofuran series is discussedread more
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Natural source, bioactivity and synthesis of benzofuran derivatives
TL;DR: A comprehensive review of recent studies on the various aspects of benzofuran derivatives including their important natural product sources, biological activities and drug prospects, and chemical synthesis, as well as the relationship between the bioactivities and structures can be found in this paper.
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An update on benzofuran inhibitors: a patent review.
TL;DR: This chapter outlines several potent benzofuran derivatives that may be useful as potential pro-drugs and the presence of -OH, -OMe, sulfonamide, or halogen contributed greatly to increasing the therapeutic activities comparing with reference drugs.
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Pd/phenanthroline-catalyzed arylative cyclization of o-(1-alkynyl)thioanisoles: synthesis of 3-arylated benzo[b]thiophenes
TL;DR: Arylative cyclization of o -(1-alkynyl)thioanisoles with aryl iodides in the presence of catalytic amounts of Pd(phen) 2 resulted in the efficient formation of 3-arylated benzo[ b ]thiophenes, and a range of aryL iodides with electron-donating or -withdrawing groups could be used.
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Synthesis and biological evaluation of novel pentacyclic triterpene α-cyclodextrin conjugates as HCV entry inhibitors.
TL;DR: A series of water-soluble triazole-bridged α-cyclodextrin-pentacyclic triterpene conjugates were easily synthesized with moderate to good yields and showed that the compounds exert their inhibitory activity at the post-binding step and subsequently prevent virus entry.
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Benzofuran-oxadiazole hybrids: Design, synthesis, antitubercular activity and molecular docking studies
Veerabhadrayya S. Negalurmath,Sathish Kumar Boda,Obelannavar Kotresh,P. V. Anantha Lakshmi,Mahantesha Basanagouda +4 more
TL;DR: In vitro antitubercular experimental results and structure activity relationship studies were supported using molecular docking studies on these novel hybrids and the highest activity of 7m superior to standard drug pyrazinamide was further supported by molecular docking results.
References
More filters
Journal ArticleDOI
Global epidemiology of hepatitis C virus infection: new estimates of age-specific antibody to HCV seroprevalence.
TL;DR: The high prevalence of global HCV infection necessitates renewed efforts in primary prevention, including vaccine development, as well as new approaches to secondary and tertiary prevention to reduce the burden of chronic liver disease and to improve survival for those who already have evidence of liver disease.
Journal Article
Prediction of human clearance of twenty-nine drugs from hepatic microsomal intrinsic clearance data: An examination of in vitro half-life approach and nonspecific binding to microsomes.
TL;DR: In the projection of human clearance values, basic and neutral compounds were well predicted when all binding considerations (blood and microsome) were disregarded, however, including both binding considerations also yielded reasonable predictions.
Journal ArticleDOI
Human immunodeficiency virus type 1 viral protein R (Vpr) arrests cells in the G2 phase of the cell cycle by inhibiting p34cdc2 activity.
TL;DR: It is shown here that Vpr arrests the cell cycle in G2 by preventing the activation of the p34cdc2/cyclin B complex that is required for entry into M phase, and in vivo, Vpr might, by preventing p34CDc2 activation, delay or prevent apoptosis of infected cells.
Journal ArticleDOI
Hepatitis C Virus p7 and NS2 Proteins Are Essential for Production of Infectious Virus
TL;DR: It is concluded that p7 and NS2 function at an early stage of virion morphogenesis, prior to the assembly of infectious virus.
Journal ArticleDOI
Challenges and successes in developing new therapies for hepatitis C
TL;DR: Preclinical evidence is accumulating that development of resistance will eventually limit the efficacy of new drugs, and combinations of multiple agents will be required to treat chronic HCV infection.