Linked Life Data

7520080

Source:http://linkedlifedata.com/resource/pubmed/id/7520080

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
16
pubmed:dateCreated
1994-9-13
pubmed:abstractText
Over 25 selected naphthalenesulfonic acid derivatives were evaluated for their inhibitory effect on two different functional domains of the HIV-1 reverse transcriptase (RT), namely the ribonuclease H and DNA polymerase activities. Most of the analogues were found to be either specific toward the DNA polymerase activity or showed nonselective inhibition of both catalytic functions. The most active compounds are either symmetrical derivatives or nonsymmetrical derivatives containing a lipophilic appendage consisting of a palmitoyl or cholesteryl moiety. The six most active compounds in the preliminary screen, derivatives 6, 16, 17, 23, 26, and 27, were subjected to experiments to determine their 50% inhibitory concentration (IC50) values in the assays that measure RNA-dependent DNA polymerase (RDDP), DNA-dependent DNA polymerase (DDDP), and ribonuclease H (RNase H) functions of HIV-1 RT. The most potent derivative was a nonsymmetric cholesterol-linked 4-amino-5-hydroxy-2,7-naphthalenedisulfonic acid analogue, compound 23, which demonstrated an IC50 value of 0.06 microM for inhibiting RDDP activity. Inhibition of DDDP and RNase H activity for this compound was demonstrated at concentrations that were over 100-fold of that for inhibiting RDDP activity. However, the potency of this active compound does not correlate in the whole virus assay, probably due to a lack of cellular entry. The cholesterol derivative, 23, also possesses HIV-1 protease inhibitory activity and belongs to a unique class of multifunctional HIV-1 inhibitors.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
5
pubmed:volume
37
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2513-9
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Synthesis of naphthalenesulfonic acid small molecules as selective inhibitors of the DNA polymerase and ribonuclease H activities of HIV-1 reverse transcriptase.
pubmed:affiliation
Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago 60680.
pubmed:publicationType
Journal Article