ArticleJournal of medicinal chemistry2016
Impact of Stepwise NH2-Methylation of Triapine on the Physicochemical Properties, Anticancer Activity, and Resistance Circumvention.
Article in Journal of medicinal chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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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.
The trial behind it
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
18 citing papers in PubMed, 50 citations in OpenAlex.
- Synthesis, characterization, crystal structures, antitumor activity, and computational study of novel thiosemicarbazone derivatives from thiazol-2/5-carbaldehyde.RSC advances · 2026Article
- Novel Pyridine-Based Thiazolyl-Hydrazone as a Promising Attenuator ofInternational journal of molecular sciences · 2026Article
- Are the metal identity and stoichiometry of metal complexes important for colchicine site binding and inhibition of tubulin polymerization?Dalton transactions (Cambridge, England : 2003) · 2024Article
- Copper(II) Complexes with Isomeric Morpholine-Substituted 2-Formylpyridine Thiosemicarbazone Hybrids as Potential Anticancer Drugs Inhibiting Both Ribonucleotide Reductase and Tubulin Polymerization: The Morpholine Position Matters.Journal of medicinal chemistry · 2024Article
- A Comparative Study on the Complexation of the Anticancer Iron Chelator VLX600 with Essential Metal Ions.Inorganic chemistry · 2024Article
- Human serum albumin as a copper source for anticancer thiosemicarbazones.Metallomics : integrated biometal science · 2023Article
- Dual Role of Glutathione as a Reducing Agent and Cu-Ligand Governs the ROS Production by Anticancer Cu-Thiosemicarbazone Complexes.Inorganic chemistry · 2023Article
- Article
- Estrone-salicylaldehyde N-methylated thiosemicarbazone hybrids and their copper complexes: solution structure, stability and anticancer activity in tumour spheroids.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2021Article
- Triapine Analogues and Their Copper(II) Complexes: Synthesis, Characterization, Solution Speciation, Redox Activity, Cytotoxicity, and mR2 RNR Inhibition.Inorganic chemistry · 2021Article
- Modulation of Intracellular Copper Levels as the Mechanism of Action of Anticancer Copper Complexes: Clinical Relevance.Biomedicines · 2021Review
- Cancer Cell Resistance Against the Clinically Investigated Thiosemicarbazone COTI-2 Is Based on Formation of Intracellular Copper Complex Glutathione Adducts and ABCC1-Mediated Efflux.Journal of medicinal chemistry · 2020Article
- Insight into the Anticancer Activity of Copper(II) 5-Methylenetrimethylammonium-Thiosemicarbazonates and Their Interaction with Organic Cation Transporters.Biomolecules · 2020Article
- Synthesis, crystal structure and antiproliferative mechanisms of gallium(iii) complexes with benzoylpyridine thiosemicarbazones.RSC advances · 2020Article
- Isoquinoline thiosemicarbazone displays potent anticancer activity withRSC medicinal chemistry · 2020Article
- Synthesis, crystal structure and Hirshfeld analysis of a crystalline compound comprising a 1/1 mixture of 1-[(1Acta crystallographica. Section E, Crystallographic communications · 2020Article
- The thiosemicarbazone MeCell death & disease · 2018Article
- Comparison of metabolic pathways of different α-N-heterocyclic thiosemicarbazones.Analytical and bioanalytical chemistry · 2018Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
One of the most promising classes of iron chelators are α-N-heterocyclic thiosemicarbazones with Triapine as the most prominent representative. In several clinical trials Triapine showed anticancer activity against hematological diseases, however, studies on solid tumors failed due to widely unknown reasons. Some years ago, it was recognized that "terminal dimethylation" of thiosemicarbazones can lead to a more than 100-fold increased activity, probably due to interactions with cellular copper depots. To better understand the structural requirements for the switch to nanomolar cytotoxicity, we systematically synthesized all eight possible N-methylated derivatives of Triapine and investigated their potential against Triapine-sensitive as well as -resistant cell lines. While only the "completely" methylated compound exerted nanomolar activity, the data revealed that all compounds with at least one N-dimethylation were not affected by acquired Triapine resistance. In addition, these compounds were highly synergistic with copper treatment accompanied by induction of reactive oxygen species and massive necrotic cell death.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.