Linked Life Data

15071767

Source:http://linkedlifedata.com/resource/pubmed/id/15071767

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2004-6-1
pubmed:abstractText
A series of N, N'-bis(aminoalkyl)-1,4-diaminoanthraquinones (aminoalkyl=2-aminoethyl, 3-aminoprop-1-yl and 4-aminobut-1-yl) was functionalized with trans-platinum DNA-binding moieties. Cytotoxicity testing in A2780 human ovarian carcinoma cells revealed high anticancer activity of the formed cationic dinuclear platinum complexes. The cationic dinuclear platinum complexes with the shortest aminoalkyl chain were shown to be the most active, which agrees with the structure-activity relationship found for the corresponding free ligands without platinum. The N, N'-bis(aminoalkyl)-1,4-diaminoanthraquinones partly circumvent cisplatin resistance, whereas their dinuclear platinum complexes were found susceptible to the resistance mechanisms in A2780cisR. The platinum complexes have resistance factors comparable to the control dinuclear complex BBR3005 [(trans-PtCl(NH3)2)2)(micro-(NH2(CH2)6NH2))](NO3)2. The 1,4-diaminoanthraquinone moiety is fluorescent, and thus the cellular processing of the compounds could be monitored by time-lapse digital fluorescence microscopy. The intercalators without platinum were shown to enter the cells within minutes. The platinum complexes enter the cells more slowly. Most likely, the positive charges of the platinum complexes hamper the diffusion through the membrane. Interestingly, the platinum complexes are processed differently than the platinum-free compounds by the cells. After 24 hours the fluorescent platinum complexes are encapsulated in large vesicles in the cytosol. Co-localization of the anthraquinone fluorescence with Lysotracker Green DND-26 shows that these vesicles are acidic compartments, probably lysosomes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0949-8257
pubmed:author
pubmed:copyrightInfo
Copyright 2004 SBIC
pubmed:issnType
Print
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
403-13
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Dinuclear platinum complexes with N, N'-bis(aminoalkyl)-1,4-diaminoanthraquinones as linking ligands. Part I. Synthesis, cytotoxicity, and cellular studies in A2780 human ovarian carcinoma cells.
pubmed:affiliation
Leiden Institute of Chemistry, Gorlaeus Laboratories, Leiden University, P.O. Box 9502, 2300 RA, Leiden, The Netherlands.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't