Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 54, Issue 15, Pages 5395-5402Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jm200242p
Keywords
-
Categories
Funding
- Ministere de l'Enseignement et de la Recherche
- l'Agence Nationale de la Recherche (ANR)
- University of Sun Yat-Sen (China)
Ask authors/readers for more resources
We have identified naturally occurring 2-benzylidenebenzofuran-3-ones (aurones) as new templates for non-nucleoside hepatitis C virus (HCV) RNA-dependent RNA polymerase (RdRp) inhibitors. The aurone target site, identified by site-directed mutagenesis, is located in thumb pocket I of HCV RdRp. The RdRp inhibitory activity of 42 aurones was rationally explored in an enzyme assay. Molecular docking studies were used to determine how aurones bind to HCV RdRp and to predict their range of inhibitory activity. Seven aurone derivatives were found to have potent inhibitory effects on HCV RdRp, with IC(50) below 5 mu M and excellent selectivity index (inhibition activity versus cellular cytotoxicity). The most active aurone analogue was (Z)-2-((1-butyl-1H-indo1-3-yl)methylene)-4,6-dihydroxybenzofuran-3(2H)-one (compound 51), with an IC(50) of 2.2 mu M. Their potent RdRp inhibitory activity and their low toxicity make these molecules attractive candidates as direct-acting anti-HCV agents.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available