Novel and potent anti-tumor and anti-metastatic di-2-pyridylketone thiosemicarbazones demonstrate marked differences in pharmacology between the first and second generation lead agents
Identifikátory výsledku
Kód výsledku v IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11150%2F15%3A10315138" target="_blank" >RIV/00216208:11150/15:10315138 - isvavai.cz</a>
Nalezeny alternativní kódy
RIV/00216208:11160/15:10315138
Výsledek na webu
<a href="http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path" target="_blank" >http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.18632/oncotarget.6389" target="_blank" >10.18632/oncotarget.6389</a>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
Novel and potent anti-tumor and anti-metastatic di-2-pyridylketone thiosemicarbazones demonstrate marked differences in pharmacology between the first and second generation lead agents
Popis výsledku v původním jazyce
Di(2-pyridyl)ketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT) and di(2-pyridyl)ketone 4-cyclohexyl-4-methyl-3-thiosemicarbazone (DpC) are novel, highly potent and selective anti-tumor and anti-metastatic drugs. Despite their structural similarity, theseagents differ in their efficacy and toxicity in-vivo. Considering this, a comparison of their pharmacokinetic and pharmaco/toxico-dynamic properties was conducted to reveal if these factors are involved in their differential activity. Both compounds wereadministered to Wistar rats intravenously (2 mg/kg) and their metabolism and disposition were studied using UHPLC-MS/MS. The cytotoxicity of both thiosemicarbazones and their metabolites was also examined using MCF-7, HL-60 and HCT116 tumor cells and 3T3 fibroblasts and H9c2 cardiac myoblasts. Their intracellular iron-binding ability was characterized by the Calcein-AM assay and their iron mobilization efficacy was evaluated. In contrast to DpC, Dp44mT undergoes rapid demethylation in-v
Název v anglickém jazyce
Novel and potent anti-tumor and anti-metastatic di-2-pyridylketone thiosemicarbazones demonstrate marked differences in pharmacology between the first and second generation lead agents
Popis výsledku anglicky
Di(2-pyridyl)ketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT) and di(2-pyridyl)ketone 4-cyclohexyl-4-methyl-3-thiosemicarbazone (DpC) are novel, highly potent and selective anti-tumor and anti-metastatic drugs. Despite their structural similarity, theseagents differ in their efficacy and toxicity in-vivo. Considering this, a comparison of their pharmacokinetic and pharmaco/toxico-dynamic properties was conducted to reveal if these factors are involved in their differential activity. Both compounds wereadministered to Wistar rats intravenously (2 mg/kg) and their metabolism and disposition were studied using UHPLC-MS/MS. The cytotoxicity of both thiosemicarbazones and their metabolites was also examined using MCF-7, HL-60 and HCT116 tumor cells and 3T3 fibroblasts and H9c2 cardiac myoblasts. Their intracellular iron-binding ability was characterized by the Calcein-AM assay and their iron mobilization efficacy was evaluated. In contrast to DpC, Dp44mT undergoes rapid demethylation in-v
Klasifikace
Druh
J<sub>x</sub> - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)
CEP obor
FR - Farmakologie a lékárnická chemie
OECD FORD obor
—
Návaznosti výsledku
Projekt
<a href="/cs/project/EE2.3.30.0061" target="_blank" >EE2.3.30.0061: Zvýšení kapacity vědecko-výzkumných týmů Univerzity Karlovy prostřednictvím nových pozic pro absolventy doktorandských studií</a><br>
Návaznosti
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Ostatní
Rok uplatnění
2015
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
Oncotarget
ISSN
1949-2553
e-ISSN
—
Svazek periodika
6
Číslo periodika v rámci svazku
40
Stát vydavatele periodika
US - Spojené státy americké
Počet stran výsledku
18
Strana od-do
42411-42428
Kód UT WoS článku
000369907900003
EID výsledku v databázi Scopus
2-s2.0-84952361788