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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2010-4-15
pubmed:abstractText
A new goup of acridone derivatives, obtained by reaction of acridone-4-carboxylic acid derivatives with aromatic amines, was tested to determine the inhibitory properties toward the NS3 helicase of hepatitis C virus (HCV). Six compounds inhibited the NS3 helicase at low concentrations (IC(50) from 1.5 to 20 microM). The acridone derivatives probably act via intercalation into double-stranded nucleic acids with a strong specificity for double-stranded RNA, although an interaction with the enzyme cannot be excluded. Testing in the subgenomic HCV replicon system revealed that compounds 10 and 13 are efficient RNA replication inhibitors, with EC(50) of 3.5 and 1 microM and therapeutic indexes of >28 and 20, respectively. Compound 16, with EC(50) < 1 microM and TI > 1000, is extremely specific and practically noncytotoxic at the concentrations tested, proving that the acridone derivatives may be regarded as potential antiviral agents. Although the mechanism of action of 16 in the replicon system remains unclear, it is the key lead compound for further development of anti-HCV drugs.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1520-4804
pubmed:author
pubmed:issnType
Electronic
pubmed:day
22
pubmed:volume
53
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3117-26
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Synthesis of new acridone derivatives, inhibitors of NS3 helicase, which efficiently and specifically inhibit subgenomic HCV replication.
pubmed:affiliation
Institute of Biochemistry and Biophysics, PAS, Pawinskiego 5a, 02-106 Warsaw, Poland.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't