Linked Life Data

14584951

Source:http://linkedlifedata.com/resource/pubmed/id/14584951

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
23
pubmed:dateCreated
2003-10-30
pubmed:abstractText
5-Chloro-1,3-dihydroxyacridone, 1, is a potent and selective inhibitor of Herpes Simplex Virus Type-1 (HSV-1).(1) Substituted 1,3-dihydroxyacridones represent a new class of nonnucleoside HSV-1 inhibitors, and biochemical studies indicate a novel mechanism of action for 1, although the target is not yet defined.(2) With the goal of lead optimization, analogues of 1 were synthesized in an effort to describe the structure-activity relationships between 1 and its hypothetical binding site. Modifications of key functional groups led to the identity of several features of 1 that were important for activity. In the process, a more expedient and reliable synthesis of 1 and its analogues was developed. Analogues were evaluated against HSV-1 and HSV-2 using a viral plaque-elimination assay for viral inhibition of HSV-1 and HSV-2, and effects on replication of the host cell were also measured in order to assess a therapeutic index (TI) of selectivity. Several new analogues with significant antiviral activity were identified, including 5-methoxy-1,3-dihydroxyacridone (11), which inhibits replication of several HSV-2 strains with a mean ED(50) of 0.7 muM and a TI range of 25-60-fold.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
6
pubmed:volume
46
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5015-20
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Anti-herpes simplex virus activity of substituted 1-hydroxyacridones.
pubmed:affiliation
Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA. Christopher.Lowden@rtp.ppdi.com
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't