ArticleBiochemistry2012
Amsacrine as a topoisomerase II poison: importance of drug-DNA interactions.
Article in Biochemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 105 citations in OpenAlex.
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- Complex mechanisms of topoisomerase II poisons revealed by whole-genome analysis.Communications biology · 2026Article
- Design and Multi-Level Biological Evaluation of Naphthyridine-Based Derivatives as Topoisomerase I/II-Targeted Anticancer Agents with Anti-Fowlpox Virus Activity Supported by In Silico Analysis.International journal of molecular sciences · 2026Article
- Quantitative high-throughput screening identifies small-molecule modulators of Wnt/β-catenin signaling.Frontiers in pharmacology · 2026Article
- A Review on Sulfonamide Complexes with Metals: Their Pharmacological Potential as Anticancer Drugs.Pharmaceuticals (Basel, Switzerland) · 2025Review
- An Overview of Acridine Analogs: Pharmacological Significance and Recent Developments.Current medicinal chemistry · 2025Review
- Role of Natural Binding Proteins in Therapy and Diagnostics.Life (Basel, Switzerland) · 2024Article
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- Targeting yeast topoisomerase II by imidazo and triazoloacridinone derivatives resulting in their antifungal activity.Scientific reports · 2024Article
- Design, synthesis and biological evaluation of tetrahydroquinoxaline sulfonamide derivatives as colchicine binding site inhibitors.RSC advances · 2023Article
- Design and synthesis of novel cytotoxic fluoroquinolone analogs through topoisomerase inhibition, cell cycle arrest, and apoptosis.Scientific reports · 2023Article
- Novel 3,9-Disubstituted Acridines with Strong Inhibition Activity against Topoisomerase I: Synthesis, Biological Evaluation and Molecular Docking Study.Molecules (Basel, Switzerland) · 2023Article
- A Mini Review of Novel Topoisomerase II Inhibitors as Future Anticancer Agents.International journal of molecular sciences · 2023Review
- Synthesis and Evaluation of Antiproliferative Activity, Topoisomerase IIα Inhibition, DNA Binding and Non-Clinical Toxicity of New Acridine-Thiosemicarbazone Derivatives.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Prostate Apoptosis Response-4 (Par-4): A Novel Target in Pyronaridine-Induced Apoptosis in Glioblastoma (GBM) Cells.Cancers · 2022Article
- Dietary Intake of Polyphenols and the Risk of Breast Cancer: a Case-Control Study.Clinical nutrition research · 2021Article
- Molecular docking analysis of α-Topoisomerase II with δ-Carboline derivatives as potential anticancer agents.Bioinformation · 2021Article
- DNA topoisomerases as molecular targets for anticancer drugs.Journal of enzyme inhibition and medicinal chemistry · 2020Review
- The GeneG3 (Bethesda, Md.) · 2020Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
Amsacrine (m-AMSA) is an anticancer agent that displays activity against refractory acute leukemias as well as Hodgkin's and non-Hodgkin's lymphomas. The drug is comprised of an intercalative acridine moiety coupled to a 4'-amino-methanesulfon-m-anisidide headgroup. m-AMSA is historically significant in that it was the first drug demonstrated to function as a topoisomerase II poison. Although m-AMSA was designed as a DNA binding agent, the ability to intercalate does not appear to be the sole determinant of drug activity. Therefore, to more fully analyze structure-function relationships and the role of DNA binding in the action of m-AMSA, we analyzed a series of derivatives for the ability to enhance DNA cleavage mediated by human topoisomerase IIα and topoisomerase IIβ and to intercalate DNA. Results indicate that the 3'-methoxy (m-AMSA) positively affects drug function, potentially by restricting the rotation of the headgroup in a favorable orientation. Shifting the methoxy to the 2'-position (o-AMSA), which abrogates drug function, appears to increase the degree of rotational freedom of the headgroup and may impair interactions of the 1'-substituent or other portions of the headgroup within the ternary complex. Finally, the nonintercalative m-AMSA headgroup enhanced enzyme-mediated DNA cleavage when it was detached from the acridine moiety, albeit with 100-fold lower affinity. Taken together, our results suggest that much of the activity and specificity of m-AMSA as a topoisomerase II poison is embodied in the headgroup, while DNA intercalation is used primarily to increase the affinity of m-AMSA for the topoisomerase II-DNA cleavage complex.
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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.