ArticleBiochemistry2011
Interactions between the etoposide derivative F14512 and human type II topoisomerases: implications for the C4 spermine moiety in promoting enzyme-mediated DNA cleavage.
Article in Biochemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 63 citations in OpenAlex.
- Molecular mechanism of a triazole-containing inhibitor ofiScience · 2024Article
- Interactions between Gepotidacin andACS infectious diseases · 2024Article
- Podophyllotoxin: Recent Advances in the Development of Hybridization Strategies to Enhance Its Antitumoral Profile.Pharmaceutics · 2023Review
- Telling Your Right Hand from Your Left: The Effects of DNA Supercoil Handedness on the Actions of Type II Topoisomerases.International journal of molecular sciences · 2023Review
- Polyamine-Drug Conjugates: Do They Boost Drug Activity?Molecules (Basel, Switzerland) · 2023Review
- Basis for the discrimination of supercoil handedness during DNA cleavage by human and bacterial type II topoisomerases.Nucleic acids research · 2023Article
- 1,2-Naphthoquinone as a Poison of Human Type II Topoisomerases.Chemical research in toxicology · 2021Article
- DNA topoisomerases as molecular targets for anticancer drugs.Journal of enzyme inhibition and medicinal chemistry · 2020Review
- 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
- Phase I dose-escalation study of F14512, a polyamine-vectorized topoisomerase II inhibitor, in patients with platinum-refractory or resistant ovarian cancer.Investigational new drugs · 2019Article
- Medicinal plants commonly used against cancer in traditional medicine formulae in Sri Lanka.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2019Review
- Polyamine-containing etoposide derivatives as poisons of human type II topoisomerases: Differential effects on topoisomerase IIα and IIβ.Bioorganic & medicinal chemistry letters · 2018Article
- Novel xanthone-polyamine conjugates as catalytic inhibitors of human topoisomerase IIα.Bioorganic & medicinal chemistry letters · 2017Article
- Article
- Effects of Secondary Metabolites from the Fungus Septofusidium berolinense on DNA Cleavage Mediated by Human Topoisomerase IIα.Chemical research in toxicology · 2016Article
- Fluoroquinolone interactions with Mycobacterium tuberculosis gyrase: Enhancing drug activity against wild-type and resistant gyrase.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Crystal structure and stability of gyrase-fluoroquinolone cleaved complexes from Mycobacterium tuberculosis.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Structural basis of DNA gyrase inhibition by antibacterial QPT-1, anticancer drug etoposide and moxifloxacin.Nature communications · 2015Article
- Effects of Olive Metabolites on DNA Cleavage Mediated by Human Type II Topoisomerases.Biochemistry · 2015Article
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
F14512 is a novel etoposide derivative that contains a spermine in place of the C4 glycosidic moiety. The drug was designed to exploit the polyamine transport system that is upregulated in some cancers. However, a preliminary study suggests that it is also a more efficacious topoisomerase II poison than etoposide [Barret et al. (2008) Cancer Res. 68, 9845-9853]. Therefore, we undertook a more complete study of the actions of F14512 against human type II topoisomerases. As determined by saturation transfer difference (1)H NMR spectroscopy, contacts between F14512 and human topoisomerase IIα in the binary enzyme-drug complex are similar to those of etoposide. Although the spermine of F14512 does not interact with the enzyme, it converts the drug to a DNA binder [Barret et al. (2008)]. Consequently, the influence of the C4 spermine on drug activity was assessed. F14512 is a highly active topoisomerase II poison and stimulates DNA cleavage mediated by human topoisomerase IIα or topoisomerase IIβ. The drug is more potent and efficacious than etoposide or TOP-53, an etoposide derivative that contains a C4 aminoalkyl group that strengthens drug-enzyme binding. Unlike the other drugs, F14512 maintains robust activity in the absence of ATP. The enhanced activity of F14512 correlates with a tighter binding and an increased stability of the ternary topoisomerase II-drug-DNA complex. The spermine-drug core linkage is critical for these attributes. These findings demonstrate the utility of a C4 DNA binding group and provide a rational basis for the development of novel and more active etoposide-based topoisomerase II poisons.
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