Linked Life Data

10496963

Source:http://linkedlifedata.com/resource/pubmed/id/10496963

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1999-10-8
pubmed:abstractText
The presence of a nitrogen atom, charged at physiological pH, has frequently been considered to be a hallmark of P-glycoprotein (PGP) inhibitors, although certain steroids, such as progesterone, lack a nitrogen atom and still are active modulators of PGP. The present study was aimed at investigating the role the nitrogen atom plays in the activity of PGP inhibitors. Propafenone-related amines, anilines, and amides that cover a broad range of pK(a) values, as well as an ester, were synthesized and tested for multidrug resistance-reverting activity. The sum of the hydrogen bond acceptor strengths was calculated and correlated with EC(50) values for PGP inhibition. For the complete set of 12 compounds, an excellent correlation between these two parameters was found; this included the ester GP570, which lacks a nitrogen atom but contains the strong hydrogen bond-accepting ester unit. The interaction of the nitrogen atom with PGP therefore is nonional and is determined by the sum of the hydrogen acceptor strengths of the region. The high predictivity of the obtained model is demonstrated in a leave-one-out cross-validation procedure.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0026-895X
pubmed:author
pubmed:issnType
Print
pubmed:volume
56
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
791-6
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
The importance of a nitrogen atom in modulators of multidrug resistance.
pubmed:affiliation
Institute of Pharmaceutical Chemistry, University of Vienna, Austria. ecker@speedy.pch.univie.ac.at
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't