Linked Life Data

15537360

Source:http://linkedlifedata.com/resource/pubmed/id/15537360

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
24
pubmed:dateCreated
2004-11-11
pubmed:abstractText
Several N(1)-arylalkylpolyamines containing various aromatic ring systems were synthesized as their respective HCl salts. The N(1)-substituents evaluated ranged in size from N(1)-benzyl, N(1)-naphthalen-1-ylmethyl, N(1)-2-(naphthalen-1-yl)ethyl, N(1)-3-(naphthalen-1-yl)propyl, N(1)-anthracen-9-ylmethyl, N(1)-2-(anthracen-9-yl)ethyl, N(1)-3-(anthracen-9-yl)propyl, and pyren-1-ylmethyl. The polyamine architecture was also altered and ranged from diamine to triamine and tetraamine systems. Biological activities in L1210 (murine leukemia), Chinese hamster ovary (CHO), and CHO's polyamine transport-deficient mutant (CHO-MG) cell lines were investigated via IC(50) cytotoxicity determinations. K(i) values for spermidine uptake were also determined in L1210 cells. The size of the N(1)-arylalkyl substituent as well as the polyamine sequence used had direct bearing on the observed cytotoxicity profiles. N(1)-Tethers longer than ethylene showed dramatic loss of selectivity for the polyamine transporter (PAT) as shown in a CHO/CHO-MG cytotoxicity screen. In summary, there are clear limits to the size of N(1)-substituents, which can be accommodated by the polyamine transporter. A direct correlation was observed between polyamine-conjugate uptake and cytotoxicity. In this regard, a cytotoxicity model was proposed, which describes a hydrophobic pocket of set dimensions adjacent to the putative PAT polyamine-binding site.
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
18
pubmed:volume
47
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6055-69
pubmed:dateRevised
2005-11-17
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
N1-substituent effects in the selective delivery of polyamine conjugates into cells containing active polyamine transporters.
pubmed:affiliation
Department of Chemistry, P.O. Box 162366, University of Central Florida, Orlando, FL 32816-2366, USA.
pubmed:publicationType
Journal Article