ArticleOncotarget2015
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.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed.
- Evolution of Thiosemicarbazones: From First- to Second-Generation Metal Chelators and Their Reactive Oxygen Species-Mediated Effects in Melanoma.ChemistryOpen · 2026Review
- Transmetalation in Cancer Pharmacology.International journal of molecular sciences · 2025Review
- Syntheses and structures of dinuclear zinc(II) acetate-bridged coordination compounds with the aromatic Schiff base chelatorsActa crystallographica. Section E, Crystallographic communications · 2025Article
- Targeting senescent hepatocytes for treatment of metabolic dysfunction-associated steatotic liver disease and multi-organ dysfunction.Nature communications · 2025Article
- Desulfurization of thiosemicarbazones: the role of metal ions and biological implications.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2024Review
- Increased Free Radical Generation during the Interaction of a Quinone-Quinoline Chelator with Metal Ions and the Enhancing Effect of Light.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Article
- Iron-Chelation Treatment by Novel Thiosemicarbazone Targets Major Signaling Pathways in Neuroblastoma.International journal of molecular sciences · 2021Article
- Modulation of Intracellular Copper Levels as the Mechanism of Action of Anticancer Copper Complexes: Clinical Relevance.Biomedicines · 2021Review
- Overcoming tamoxifen resistance in oestrogen receptor-positive breast cancer using the novel thiosemicarbazone anti-cancer agent, DpC.British journal of pharmacology · 2020Article
- Novel multifunctional iron chelators of the aroyl nicotinoyl hydrazone class that markedly enhance cellular NADBritish journal of pharmacology · 2020Article
- UHPLC-MS/MS method for analysis of sobuzoxane, its active form ICRF-154 and metabolite EDTA-diamide and its application to bioactivation study.Scientific reports · 2019Article
- Comparison of metabolic pathways of different α-N-heterocyclic thiosemicarbazones.Analytical and bioanalytical chemistry · 2018Article
- Article
- Synthesis and Evaluation of New Benzodioxole- Based Thiosemicarbazone Derivatives as Potential Antitumor Agents.Molecules (Basel, Switzerland) · 2016Article
- The novel thiosemicarbazone, di-2-pyridylketone 4-cyclohexyl-4-methyl-3-thiosemicarbazone (DpC), inhibits neuroblastoma growth in vitro and in vivo via multiple mechanisms.Journal of hematology & oncology · 2016Article
- Copper that cancer with lysosomal love!Aging · 2016Article
Corrections and comments
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Authors and funding
15 authors.
Funding
No grant is acknowledged in the PubMed record.
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. 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-vivo, which may be related to its markedly faster elimination (T1/2 = 1.7 h for Dp44mT vs. 10.7 h for DpC) and lower exposure. Incubation of these compounds with cancer cells or cardiac myoblasts did not result in any significant metabolism in-vitro. The metabolism of Dp44mT in-vivo resulted in decreased anti-cancer activity and toxicity. In conclusion, marked differences in the pharmacology of Dp44mT and DpC were observed and highlight the favorable pharmacokinetics of DpC for cancer treatment.
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