Linked Life Data

12017367

Source:http://linkedlifedata.com/resource/pubmed/id/12017367

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2002-5-17
pubmed:abstractText
Macrolide antibiotics have recently triggered much interest owing to the immunomodulatory potential of some derivatives, particularly in the field of inflammatory diseases. Among the possible mechanisms underlying these anti-inflammatory effects, macrolide-induced inhibition of oxidant production by phagocytes has attracted much attention. We and others have previously reported that erythromycin A-derived macrolides impair the phagocyte oxidative burst, a property linked to the presence of L-cladinose. However, we have also demonstrated that other substituents can be involved in the modulation of phagocyte function. Here we have extended the analysis of structure-activity relationships by studying the effects of five 9-N-alkyl derivatives of erythromycylamine on oxidant production by human neutrophils in vitro. LY211397 (2-methoxyethyl derivative) neither altered cell viability nor superoxide anion production. LY281389 (n-propyl derivative) did not alter cell viability and was slightly more inhibitory than erythromycylamine for the production of superoxide anion; its IC50 (concentration that inhibits 50% of the neutrophil response) was about 18 and 24 microM (versus 72 and 74 pM for erythromycylamine) after 60 min of incubation following fMLP and PMA stimulation, respectively. LY80576 (N-phenyl-3-indolylmethyl derivative), LY281981 (3-phenyl-n-propyl derivative) and LY57843 (benzyl derivative) all displayed cellular toxicity at high pharmacological concentrations after 30 to 60 min of incubation. Interestingly, these latter three drugs exhibited a rapid (5 min incubation) and strong inhibitory effect on the neutrophil oxidative burst from either stimulus, with IC50 values of 3 to 10 pM. Further in-vitro and in-vivo investigations are required to analyze the anti-inflammatory potential of these three derivatives.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1120-009X
pubmed:author
pubmed:issnType
Print
pubmed:volume
14
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
132-9
pubmed:dateRevised
2009-8-4
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Structure-activity relationships among 9-N-alkyl derivatives of erythromycylamine and their effect on the oxidative burst of human neutrophils in vitro.
pubmed:affiliation
Faculté des Science I, Ain Chock, Casablanca, Morrocco.
pubmed:publicationType
Journal Article