Linked Life Data

21536448

Source:http://linkedlifedata.com/resource/pubmed/id/21536448

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2011-5-25
pubmed:abstractText
Amino-bisphosphonates (alendronate, pamidronate) were covalently linked in a three step synthesis, with protected and triazolylated derivatives of therapeutically used nucleoside analogs (5-FdU, araC, AZT) by substitution of their triazolyl residue. From the deprotected and chromatographically purified reaction mixtures N?-[alkyl-(hydroxyphosphono) phosphonate]-cytidine combining two differently cytotoxic functions were obtained. This new family of bisphosphonates (BPs) contains as novelty an alkyl side chain with a cytotoxic nucleoside. The BPs moiety allows for a high binding to hydroxyapatite which is a prerequisite for bone targeting of the drugs. In vitro binding of 5-FdU-alendronate (5-FdU-ale) to hydroxyapatite showed a sixfold increased binding of these BPs as compared to 5-FdU. Exploratory cytotoxic properties of 5-FdU-ale were tested on a panel of human tumor cell lines resulting in growth inhibition ranging between 5% and 38%. The determination of IC??-concentrations of the conjugate in Lewis lung carcinoma and murine macrophages showed an incubation time dependent growth inhibition with higher sensitivity towards the tumor cells. We assume that the antimetabolite-BPs can be cleaved into different active metabolites that may exert cytotoxic and other therapeutic effects. However, the underlying mechanisms of these promising new antimetabolite-BPs conjugates remain to be evaluated in future experiments.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1464-3391
pubmed:author
pubmed:copyrightInfo
Copyright © 2011 Elsevier Ltd. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
19
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3520-6
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
N?-[Alkyl-(hydroxyphosphono)phosphonate]-cytidine-new drugs covalently linking antimetabolites (5-FdU, araU or AZT) with bone-targeting bisphosphonates (alendronate or pamidronate).
pubmed:affiliation
Institute for Organic Chemistry, University of Tuebingen, Tuebingen, Germany. herbert.schott@uni-tuebingen.de
pubmed:publicationType
Journal Article