ArticleBioorganic & medicinal chemistry letters2018
Polyamine-containing etoposide derivatives as poisons of human type II topoisomerases: Differential effects on topoisomerase IIα and IIβ.
Article in Bioorganic & medicinal chemistry letters, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 16 citations in OpenAlex.
- Design and Synthesis of Polyamine-Proteolysis Targeting Chimera Conjugates for Histone Deacetylase (HDAC) Degradation with Enhanced Cellular Uptake.ChemistryOpen · 2026Article
- Tetrahydropyrido[4,3-d]pyrimidines as a new active scaffold for human topoisomerase II inhibitors.Scientific reports · 2025Article
- Etoposide, cisplatin, and sintilimab combined with anlotinib in successful treatment of adrenocortical carcinoma with lung metastasis: a case report.Frontiers in oncology · 2024Article
- Podophyllotoxin: Recent Advances in the Development of Hybridization Strategies to Enhance Its Antitumoral Profile.Pharmaceutics · 2023Review
- Polyamine-Drug Conjugates: Do They Boost Drug Activity?Molecules (Basel, Switzerland) · 2023Review
- A Mini Review of Novel Topoisomerase II Inhibitors as Future Anticancer Agents.International journal of molecular sciences · 2023Review
- EDP-M plus sintilimab in the treatment of adrenocortical carcinoma: a case report.Translational cancer research · 2022Article
- Novel, Potent, and Druglike Tetrahydroquinazoline Inhibitor That Is Highly Selective for Human Topoisomerase II α over β.Journal of medicinal chemistry · 2020Article
- Design, Synthesis, Dynamic Docking, Biochemical Characterization, andJournal of medicinal chemistry · 2020Article
- Covalent Complex of DNA and Bacterial Topoisomerase: Implications in Antibacterial Drug Development.ChemMedChem · 2020Article
- Article
- Smoothed Potential MD Simulations for Dissociation Kinetics of Etoposide To Unravel Isoform Specificity in Targeting Human Topoisomerase II.Journal of chemical information and modeling · 2019Article
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Etoposide is an anticancer drug that acts by inducing topoisomerase II-mediated DNA cleavage. Despite its wide use, etoposide is associated with some very serious side-effects including the development of treatment-related acute myelogenous leukemias. Etoposide targets both human topoisomerase IIα and IIβ. However, the contributions of the two enzyme isoforms to the therapeutic vs. leukemogenic properties of the drug are unclear. In order to develop an etoposide-based drug with specificity for cancer cells that express an active polyamine transport system, the sugar moiety of the drug has been replaced with a polyamine tail. To analyze the effects of this substitution on the specificity of hybrid molecules toward the two enzyme isoforms, we analyzed the activity of a series of etoposide-polyamine hybrids toward human topoisomerase IIα and IIβ. All of the compounds displayed an ability to induce enzyme-mediated DNA cleavage that was comparable to or higher than that of etoposide. Relative to the parent drug, the hybrid compounds displayed substantially higher activity toward topoisomerase IIβ than IIα. Modeling studies suggest that the enhanced specificity may result from interactions with Gln778 in topoisomerase IIβ. The corresponding residue in the α isoform is a methionine.
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