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

Vit Sestak, Jan Stariat, Jolana Cermanova, Eliska Potuckova, Jaroslav Chladek, Jaroslav Roh, Jan Bures, Hana Jansova, Petr Prusa, Martin Sterba, Stanislav Micuda, Tomas Simunek, Danuta S Kalinowski, Des Richardson, Petra Kovarikova

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

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, these agents 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 were administered 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.
Original languageEnglish
Pages (from-to)42411-42428
Number of pages18
JournalOncotarget
Volume6
Issue number40
DOIs
Publication statusPublished - 2015

Fingerprint Dive into the research topics of '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'. Together they form a unique fingerprint.

  • Cite this

    Sestak, V., Stariat, J., Cermanova, J., Potuckova, E., Chladek, J., Roh, J., Bures, J., Jansova, H., Prusa, P., Sterba, M., Micuda, S., Simunek, T., Kalinowski, D. S., Richardson, D., & Kovarikova, P. (2015). 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. Oncotarget, 6(40), 42411-42428. https://doi.org/10.18632/oncotarget.6389