Document Detail


Novel triacsin C analogs as potential antivirals against rotavirus infections.
MedLine Citation:
PMID:  22365411     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Recently our group has demonstrated that cellular triglyceride (TG) levels play an important role in rotavirus replication. In this study, we further examined the roles of the key enzymes for TG synthesis (lipogenesis) in the replication of rotaviruses by using inhibitors of fatty acid synthase, long chain fatty acid acyl-CoA synthetase (ACSL), and diacylglycerol acyltransferase and acyl-CoA:cholesterol acyltransferase in association with lipid droplets of which TG is a major component. Triacsin C, a natural ACSL inhibitor from Streptomyces aureofaciens, was found to be highly effective against rotavirus replication. Thus, novel triacsin C analogs were synthesized and evaluated for their efficacies against the replication of rotaviruses in cells. Many of the analogs significantly reduced rotavirus replication, and one analog (1e) was highly effective at a nanomolar concentration range (ED(50) 0.1μM) with a high therapeutic index in cell culture. Our results suggest a crucial role of lipid metabolism in rotavirus replication, and triacsin C and/or its analogs as potential therapeutic options for rotavirus infections.
Authors:
Yunjeong Kim; David George; Allan M Prior; Keshar Prasain; Shuanghong Hao; Duy D Le; Duy H Hua; Kyeong-Ok Chang
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-02-11
Journal Detail:
Title:  European journal of medicinal chemistry     Volume:  50     ISSN:  1768-3254     ISO Abbreviation:  Eur J Med Chem     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-03-19     Completed Date:  2012-07-20     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  0420510     Medline TA:  Eur J Med Chem     Country:  France    
Other Details:
Languages:  eng     Pagination:  311-8     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Masson SAS. All rights reserved.
Affiliation:
Department of Diagnostic Medicine and Pathobiology, College of Veterinary Medicine, Kansas State University, 1800 Denison Avenue, Manhattan, KS 66506, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antiviral Agents / chemical synthesis,  pharmacology*
Cells, Cultured
Fatty Acids / metabolism
Lipid Metabolism
Rotavirus / drug effects*
Rotavirus Infections / drug therapy*,  virology
Streptomyces / chemistry
Swine
Triazenes / chemistry*,  pharmacology*
Virus Replication / drug effects*
Grant Support
ID/Acronym/Agency:
U01 AI081891-03/AI/NIAID NIH HHS; U01AI081891/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Antiviral Agents; 0/Fatty Acids; 0/Triazenes; 76896-80-5/triacsin C
Comments/Corrections

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