This HTML5 document contains 59 embedded RDF statements represented using HTML+Microdata notation.

The embedded RDF content will be recognized by any processor of HTML5 Microdata.

Namespace Prefixes

PrefixIRI
dctermshttp://purl.org/dc/terms/
n6http://localhost/temp/predkladatel/
n13http://linked.opendata.cz/resource/domain/vavai/riv/tvurce/
n17http://linked.opendata.cz/resource/domain/vavai/subjekt/
n16http://linked.opendata.cz/ontology/domain/vavai/
n7http://linked.opendata.cz/resource/domain/vavai/zamer/
shttp://schema.org/
skoshttp://www.w3.org/2004/02/skos/core#
rdfshttp://www.w3.org/2000/01/rdf-schema#
n3http://linked.opendata.cz/ontology/domain/vavai/riv/
n19http://bibframe.org/vocab/
n2http://linked.opendata.cz/resource/domain/vavai/vysledek/
rdfhttp://www.w3.org/1999/02/22-rdf-syntax-ns#
n12http://linked.opendata.cz/ontology/domain/vavai/riv/klicoveSlovo/
n21http://linked.opendata.cz/ontology/domain/vavai/riv/duvernostUdaju/
xsdhhttp://www.w3.org/2001/XMLSchema#
n14http://linked.opendata.cz/ontology/domain/vavai/riv/jazykVysledku/
n10http://linked.opendata.cz/ontology/domain/vavai/riv/aktivita/
n20http://linked.opendata.cz/ontology/domain/vavai/riv/obor/
n5http://linked.opendata.cz/ontology/domain/vavai/riv/druhVysledku/
n9http://linked.opendata.cz/resource/domain/vavai/vysledek/RIV%2F00216208%3A11160%2F12%3A10124972%21RIV13-MSM-11160___/
n8http://reference.data.gov.uk/id/gregorian-year/

Statements

Subject Item
n2:RIV%2F00216208%3A11160%2F12%3A10124972%21RIV13-MSM-11160___
rdf:type
skos:Concept n16:Vysledek
rdfs:seeAlso
http://link.springer.com/article/10.1007%2Fs00216-012-5766-4
dcterms:description
The iron chelator, 2-benzoylpyridine-4-ethyl-3-thiosemicarbazone (Bp4eT), was identified as a lead compound of the 2-benzoylpyridine thiosemicarbazone series, which were designed as potential anti-cancer agents. This ligand has been shown to possess potent anti-proliferative activity with a highly selective mechanism of action. However, further progress in the development of this compound requires data regarding its metabolism in mammals. The aim of this study was to identify the main in vitro and in vivo phase I metabolites of Bp4eT using liquid chromatography tandem mass spectrometry (LC-MS/MS). Two metabolites were detected after incubation of this drug with rat and human liver microsomal fractions. Based on LC-MSn analysis, the metabolites were demonstrated to be 2-benzoylpyridine-4-ethyl-3-semicarbazone and N (3)-ethyl-N (1)-[phenyl(pyridin-2-yl)methylene]formamidrazone, with both resulting from the oxidation of the thiocarbonyl group. The identity of these metabolites was further shown by LC-MS/MS analysis of these latter compounds which were prepared by oxidation of Bp4eT with hydrogen peroxide and their structures confirmed by nuclear magnetic resonance and infrared spectra. Both the semicarbazone and the amidrazone metabolites were detected in plasma, urine, and feces after i.v. administration of Bp4eT to rats. In addition, another metabolite that could correspond to hydroxylated amidrazone was found in vivo. Thus, oxidative pathways play a major role in the phase I metabolism of this promising anti-tumor agent. The outcomes of this study will be further utilized for: (1) the development and validation of the analytical method for the quantification of Bp4eT and its metabolites in biological materials; (2) to design pharmacokinetic experiments; and to (3) evaluate the potential contribution of the individual metabolites to the pharmacodynamics/toxico-dynamics of this novel anti-proliferative agent. The iron chelator, 2-benzoylpyridine-4-ethyl-3-thiosemicarbazone (Bp4eT), was identified as a lead compound of the 2-benzoylpyridine thiosemicarbazone series, which were designed as potential anti-cancer agents. This ligand has been shown to possess potent anti-proliferative activity with a highly selective mechanism of action. However, further progress in the development of this compound requires data regarding its metabolism in mammals. The aim of this study was to identify the main in vitro and in vivo phase I metabolites of Bp4eT using liquid chromatography tandem mass spectrometry (LC-MS/MS). Two metabolites were detected after incubation of this drug with rat and human liver microsomal fractions. Based on LC-MSn analysis, the metabolites were demonstrated to be 2-benzoylpyridine-4-ethyl-3-semicarbazone and N (3)-ethyl-N (1)-[phenyl(pyridin-2-yl)methylene]formamidrazone, with both resulting from the oxidation of the thiocarbonyl group. The identity of these metabolites was further shown by LC-MS/MS analysis of these latter compounds which were prepared by oxidation of Bp4eT with hydrogen peroxide and their structures confirmed by nuclear magnetic resonance and infrared spectra. Both the semicarbazone and the amidrazone metabolites were detected in plasma, urine, and feces after i.v. administration of Bp4eT to rats. In addition, another metabolite that could correspond to hydroxylated amidrazone was found in vivo. Thus, oxidative pathways play a major role in the phase I metabolism of this promising anti-tumor agent. The outcomes of this study will be further utilized for: (1) the development and validation of the analytical method for the quantification of Bp4eT and its metabolites in biological materials; (2) to design pharmacokinetic experiments; and to (3) evaluate the potential contribution of the individual metabolites to the pharmacodynamics/toxico-dynamics of this novel anti-proliferative agent.
dcterms:title
LC-MS/MS identification of the principal in vitro and in vivo phase I metabolites of the novel thiosemicarbazone anti-cancer drug, Bp4eT LC-MS/MS identification of the principal in vitro and in vivo phase I metabolites of the novel thiosemicarbazone anti-cancer drug, Bp4eT
skos:prefLabel
LC-MS/MS identification of the principal in vitro and in vivo phase I metabolites of the novel thiosemicarbazone anti-cancer drug, Bp4eT LC-MS/MS identification of the principal in vitro and in vivo phase I metabolites of the novel thiosemicarbazone anti-cancer drug, Bp4eT
skos:notation
RIV/00216208:11160/12:10124972!RIV13-MSM-11160___
n16:predkladatel
n17:orjk%3A11160
n3:aktivita
n10:I n10:S n10:Z
n3:aktivity
I, S, Z(MSM0021620822)
n3:cisloPeriodika
1
n3:dodaniDat
n8:2013
n3:domaciTvurceVysledku
n13:9894918 n13:3249719 n13:7291787 n13:6128688 n13:9864202 n13:3923223 n13:7823983
n3:druhVysledku
n5:J
n3:duvernostUdaju
n21:S
n3:entitaPredkladatele
n9:predkladatel
n3:idSjednocenehoVysledku
146581
n3:idVysledku
RIV/00216208:11160/12:10124972
n3:jazykVysledku
n14:eng
n3:klicovaSlova
LC-MS; Anti-tumor chemotherapeutic; Anti-cancer; Bp4eT; 2-Benzoylpyridine-4-ethyl-3-thiosemicarbazone
n3:klicoveSlovo
n12:2-Benzoylpyridine-4-ethyl-3-thiosemicarbazone n12:Bp4eT n12:Anti-cancer n12:Anti-tumor%20chemotherapeutic n12:LC-MS
n3:kodStatuVydavatele
DE - Spolková republika Německo
n3:kontrolniKodProRIV
[FFC41B12E74A]
n3:nazevZdroje
Analytical and Bioanalytical Chemistry
n3:obor
n20:CB
n3:pocetDomacichTvurcuVysledku
7
n3:pocetTvurcuVysledku
9
n3:rokUplatneniVysledku
n8:2012
n3:svazekPeriodika
403
n3:tvurceVysledku
Kalinowski, Danuta S. Klimeš, Jiří Šesták, Vít Stariat, Ján Nobilis, Milan Kollárová, Zuzana Richardson, Des R. Kovaříková, Petra Vávrová, Kateřina
n3:wos
000301839700025
n3:zamer
n7:MSM0021620822
s:issn
1618-2642
s:numberOfPages
13
n19:doi
10.1007/s00216-012-5766-4
n6:organizacniJednotka
11160