ArticleJournal of chemical information and modeling2020
Substituted 4,5'-Bithiazoles as Catalytic Inhibitors of Human DNA Topoisomerase IIα.
Article in Journal of chemical information and modeling, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed.
- Discovery of Bis-Thiourea Derivatives as Human DNA Topoisomerase IIα Inhibitors with Potent Anticancer Effects.ACS omega · 2026Article
- Topoisomerase I/II inhibitors: from established drugs to next-generation therapeutics.Inflammopharmacology · 2026Review
- Farnesiferol C enhances the effects of chemotherapy and ionising radiation in human melanoma cells via targeting topoisomerase II alpha.Journal of enzyme inhibition and medicinal chemistry · 2025Article
- Synthesis,Journal of enzyme inhibition and medicinal chemistry · 2025Article
- Advances in research on malignant tumors and targeted agents for TOP2A (Review).Molecular medicine reports · 2025Review
- Palindromic carbazole derivatives: unveiling their antiproliferative effect via topoisomerase II catalytic inhibition and apoptosis induction.Journal of enzyme inhibition and medicinal chemistry · 2024Article
- Simulation- and AI-directed optimization of 4,6-substituted 1,3,5-triazin-2(1Computational and structural biotechnology journal · 2024Article
- Chemical composition of anti-microbially active fractions derived from extract of filamentous fungus Keratinophyton Lemmensii including three novel bioactive compounds.Scientific reports · 2024Article
- Synthesis of Tetracyclic Spirooxindolepyrrolidine-Engrafted Hydantoin Scaffolds: Crystallographic Analysis, Molecular Docking Studies and Evaluation of Their Antimicrobial, Anti-Inflammatory and Analgesic Activities.Molecules (Basel, Switzerland) · 2023Article
- Novel Thiazolidine-2,4-dione-trimethoxybenzene-thiazole Hybrids as Human Topoisomerases Inhibitors.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Phenotypic Discovery of Thiocarbohydrazone with Anticancer Properties and Catalytic Inhibition of Human DNA Topoisomerase IIα.Pharmaceuticals (Basel, Switzerland) · 2023Article
- A Mini Review of Novel Topoisomerase II Inhibitors as Future Anticancer Agents.International journal of molecular sciences · 2023Review
- Lestaurtinib induces DNA damage that is related to estrogen receptor activation.Current research in toxicology · 2023Article
- Unveiling the interdomain dynamics of type II DNA topoisomerase through all-atom simulations: Implications for understanding its catalytic cycle.Computational and structural biotechnology journal · 2023Article
- Catalytic Mechanism of ATP Hydrolysis in the ATPase Domain of Human DNA Topoisomerase IIα.Journal of chemical information and modeling · 2022Article
- Dynophore-Based Approach in Virtual Screening: A Case of Human DNA Topoisomerase IIα.International journal of molecular sciences · 2021Article
- Anticancer Activity of Indeno[1,2-b]-Pyridinol Derivative as a New DNA Minor Groove Binding Catalytic Inhibitor of Topoisomerase IIα.Biomolecules & therapeutics · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human type II topoisomerases, molecular motors that alter the DNA topology, are a major target of modern chemotherapy. Groups of catalytic inhibitors represent a new approach to overcome the known limitations of topoisomerase II poisons such as cardiotoxicity and induction of secondary tumors. Here, we present a class of substituted 4,5'-bithiazoles as catalytic inhibitors targeting the human DNA topoisomerase IIα. Based on a structural comparison of the ATPase domains of human and bacterial type II topoisomerase, a focused chemical library of 4,5'-bithiazoles was assembled and screened to identify compounds that better fit the topology of the human topo IIα adenosine 5'-triphosphate (ATP) binding site. Selected compounds showed inhibition of human topo IIα comparable to that of the etoposide topo II drug, revealing a new class of inhibitors targeting this molecular motor. Further investigations showed that compounds act as catalytic inhibitors via competitive ATP inhibition. We also confirmed binding to the truncated ATPase domain of topo IIα and modeled the inhibitor molecular recognition with molecular simulations and dynophore models. The compounds also displayed promising cytotoxicity against HepG2 and MCF-7 cell lines comparable to that of etoposide. In a more detailed study with the HepG2 cell line, there was no induction of DNA double-strand breaks (DSBs), and the compounds were able to reduce cell proliferation and stop the cell cycle mainly in the G1 phase. This confirms the mechanism of action of these compounds, which differs from topo II poisons also at the cellular level. Substituted 4,5'-bithiazoles appear to be a promising class for further development toward efficient and potentially safer cancer therapies exploiting the alternative topo II inhibition paradigm.
Indexed as
Identifiers
What OpenQuestion holds
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.