Linked Life Data

7629800

Source:http://linkedlifedata.com/resource/pubmed/id/7629800

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
14
pubmed:dateCreated
1995-9-1
pubmed:abstractText
A new family of chelating agents based on 4-(substituted-carbamoyl)-3-hydroxy-2-pyridinones is reported. These have optional terminal substituents on the nitrogens, and the hydroxypyridonate (HOPO) rings are attached to molecular backbones through amide linkages. A very important feature of the methyl-substituted ligand derivatives (Me-3,2-HOPOs) is that, similarly to the catechoylamide complexes of the siderophore enterobactin and its analogs, these HOPO derivatives form strong hydrogen bonds between the amide proton and the adjacent oxygen of the phenolate in the metal complex; this enhances the stability of the complex. This rigidity helps to explain the great affinity of the Me-3,2-HOPO ligands for plutonium(IV), as observed here under physiological conditions. All 13 compounds studied significantly enhanced Pu excretion from mice compared with Pu-injected controls. Eight of the ligands studied promoted significantly more Pu excretion than an equal molar amount of CaNa3-DTPA (the compound in present clinical use). Five injected and two orally administered Me-3,2-HOPO ligands promoted as much or slightly more Pu excretion than an equal molar amount of the octadentate 3,4,3-LI(1,2-HOPO), the previously most effective in vivo ligand. Surprisingly, although plutonium has an eight-coordination requirement, tetra- and hexadentate Me-3,2-HOPO ligands were essentially as effective as the one octadentate ligand studied. These observations suggest that even the tetradentate Me-3,2-HOPO ligands compete with mammalian transferrin for Pu(IV). For the three most promising compounds, there is no acute toxicity seen up to the highest dose administered, which was 1000 mumol/kg. One compound, the hexadentate TREN-(Me-3,2-HOPO), is particularly effective, either injected or orally, and an exceptionally good in vivo chelator of several actinides in addition to Pu(IV). Three of these compounds studied have low toxicity and are relatively simple and inexpensive to prepare. They are promising therapeutic agents.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
7
pubmed:volume
38
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2606-14
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
Specific sequestering agents for the actinides. 28. Synthesis and initial evaluation of multidentate 4-carbamoyl-3-hydroxyl-1-methyl-2(1H)-pyridinone ligands for in vivo plutonium(IV) chelation.
pubmed:affiliation
Department of Chemistry, University of California, Berkeley 94720, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.