Linked Life Data

14971898

Source:http://linkedlifedata.com/resource/pubmed/id/14971898

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2004-2-19
pubmed:abstractText
New formamidine-3TC (3TC = 2',3'-dideoxy-3'-thiacytidine) analogues have been synthesized through various methods, and their antiviral activities (HIV, HBV) have been evaluated in vitro. Anti-HIV-1 in acutely infected MT-4 cells and peripheral blood monocellular cells (PBMCs) showed that compounds substituted by N,N-diarylformamidine side chains at the 4-N nucleic base position (compounds 3 and 8-11) had at least equivalent anti-HIV activity as 3TC (EC50 = 0.5 and 11.6 microM, respectively). Moreover, the newly synthesized compounds demonstrated higher anti-HBV activity (EC50 ranging from 0.01 to 0.05 microM) compared to the parent nucleoside 3TC (EC50 = 0.2 microM). It should be underlined that these new promising derivatives inhibited HIV in cells of a macrophage lineage, which are known to be cellular reservoir for HIV. These results were particularly of interest, since the antiviral activities appeared not to be mediated through the formamidine bond hydrolysis and consequently the release of free 3TC. These new analogue series were found to be highly stable to hydrolysis even after prolonged incubation in different biological media (t(1/2) ranged from 48 to 120 h). This enzymatic stability, coupled to the fact that no delay in the antiviral response was observed compared to the free 3TC antiviral response, suggest that this new N,N-diarylformamidine nucleoside series should not be considered as classical prodrugs.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
26
pubmed:volume
47
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1183-92
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Potent nonclassical nucleoside antiviral drugs based on the N,N-diarylformamidine concept.
pubmed:affiliation
Laboratoire de Chimie Biomoléculaire, INSERM U 382, Developmental Biology Institute of Marseille (IBDM), Université Méditerranée, Parc Scientifique et Technologique de Luminy, 163 avenue de Luminy, case 901, 13288 Marseille 9, France.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't