Linked Life Data

17256924

Source:http://linkedlifedata.com/resource/pubmed/id/17256924

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2007-2-15
pubmed:abstractText
Enzyme-mediated cancer imaging and therapy (EMCIT) is a novel approach in which radioactive water-soluble molecules are precipitated in vivo following their hydrolysis by extracellular enzymes overexpressed by cancer cells. AutoDock 3.0 was used to model the interaction-binding between a series of iodinated quinazolinone derivatives and human placental alkaline phosphatase (PLAP, crystal structure in the Protein Data Bank) and to assess the effects of structural modification of the derivatives. Ammonium 2-(2',4'-diphosphoryloxyphenyl)-6-iodo-4-(3H)-quinazolinone (IQ2-P,4-P), having the most favorable calculated inhibition constant, was synthesized and characterized. Concentration-dependent, PLAP-mediated conversion of IQ2-P,4-P (4)/125IQ2-P,4-P (6) to water-insoluble 2-(2',4'-dihydroxyphenyl)-6-[127I/125I]iodo-4-(3H)-quinazolinone (127IQ2-OH,4-OH (2)/125IQ2-OH,4-OH (7)) was observed in solution. Autoradiography indicated that 6 is hydrolyzed by human cancer cells and the resulting 7 precipitates on exterior cell surfaces. Biodistribution studies in mice demonstrated that 6 is minimally retained by normal tissues. The findings support the validity of the EMCIT approach.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
22
pubmed:volume
50
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
663-73
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Molecular-docking-guided design, synthesis, and biologic evaluation of radioiodinated quinazolinone prodrugs.
pubmed:affiliation
Department of Radiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S.