Linked Life Data

1409376

Source:http://linkedlifedata.com/resource/pubmed/id/1409376

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
1992-11-16
pubmed:abstractText
In an attempt to generate derivatives of 5-iodo-2'-deoxyuridine (IDU) with enhanced blood-brain barrier (BBB) permeability, a series of 5' ester prodrugs of IDU was synthesized and their metabolism studied in rat brain homogenate and its different subcellular fractions. The rate of hydrolysis was dependent on the steric and polar nature of the ester substituent. Ester hydrolyzing activities were associated primarily with the cytosolic fraction and were due mainly to the presence of cholinesterases as confirmed by inhibition experiments performed with different esterase inhibitors. The metabolism of IDU to 5-iodouracil (5-IU) by the cytosolic fraction, in the presence and absence of specific pyrimidine nucleoside phosphorylase inhibitors, also suggests that there are two specific enzyme systems catalyzing two different metabolic processes. IDU 5'-esters competitively inhibit the metabolism of IDU and the inhibitory effect depends on the affinity of a particular ester toward the enzyme and also on the rate by which the ester itself undergoes hydrolysis. In the absence of any 5'-ester, 95% IDU was metabolized within 6 hr. However, in the presence of an eightfold molar excess of butyryl-IDU, the hydrolysis of IDU was completely inhibited over a 6-hr time period.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0724-8741
pubmed:author
pubmed:issnType
Print
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1048-52
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1992
pubmed:articleTitle
Brain parenchymal metabolism of 5-iodo-2'-deoxyuridine and 5'-ester prodrugs.
pubmed:affiliation
Department of Industrial and Physical Pharmacy, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, Indiana 47907.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't