ArticleNucleic acids research2006
Differential induction of Leishmania donovani bi-subunit topoisomerase I-DNA cleavage complex by selected flavones and camptothecin: activity of flavones against camptothecin-resistant topoisomerase I.
Article in Nucleic acids research, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It carries an expression of concern. Cited by 22 papers, 1 of them a synthesis that pooled it.
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
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 80 citations in OpenAlex.
- The Search for Drugs Derived from Natural Products forCurrent topics in medicinal chemistry · 2024Pooled it
- Arginine methylation of human DNA topoisomerase I by PRMT5 facilitates DNA relaxation.Nucleic acids research · 2026Article
- Flavonoids as Dual Topoisomerase I and II Inhibitors: Mechanistic Insights and Emerging Anticancer Strategies.Chemistry & biodiversity · 2026Review
- Inhibition of Antioxidant Genes Expression in Echinococcus Granulosus by Baicalein: Implications for Novel Antiparasitic Strategies.Acta parasitologica · 2026Article
- Therapeutic effect of baicalein as an antiparasitic agent againstJournal of Zhejiang University. Science. B · 2025Article
- Quercetin as a Promising Antiprotozoan Phytochemical: Current Knowledge and Future Research Avenues.BioMed research international · 2024Review
- Baicalein as Promising Anticancer Agent: A Comprehensive Analysis on Molecular Mechanisms and Therapeutic Perspectives.Cancers · 2023Review
- Chemical Characterization and Leishmanicidal Activity In Vitro and In Silico of Natural Products Obtained from Leaves ofMetabolites · 2023Article
- Natural Products That Target the Arginase inMicroorganisms · 2021Review
- Article
- Analysis of Base Excision and Single-Strand Break Repair Activities in Trypanosomatid Extracts.Methods in molecular biology (Clifton, N.J.) · 2020Article
- Neutral Porphyrin Derivative Exerts Anticancer Activity by Targeting Cellular Topoisomerase I (Top1) and Promotes Apoptotic Cell Death without Stabilizing Top1-DNA Cleavage Complexes.Journal of medicinal chemistry · 2018Article
- A Novel Spirooxindole Derivative Inhibits the Growth of Leishmania donovani Parasites both In Vitro and In Vivo by Targeting Type IB Topoisomerase.Antimicrobial agents and chemotherapy · 2016Article
- Poly(ADP-ribose) polymers regulate DNA topoisomerase I (Top1) nuclear dynamics and camptothecin sensitivity in living cells.Nucleic acids research · 2016Article
- Identification of Leishmania donovani Topoisomerase 1 inhibitors via intuitive scaffold hopping and bioisosteric modification of known Top 1 inhibitors.Scientific reports · 2016Article
- Trypanosomatids topoisomerase re-visited. New structural findings and role in drug discovery.International journal for parasitology. Drugs and drug resistance · 2014Review
- Isobenzofuranone derivatives exhibit antileishmanial effect by inhibiting type II DNA topoisomerase and inducing host response.Pharmacology research & perspectives · 2014Article
- Flavone-resistant Leishmania donovani overexpresses LdMRP2 transporter in the parasite and activates host MRP2 on macrophages to circumvent the flavone-mediated cell death.The Journal of biological chemistry · 2014Article
- Fluorescence spectroscopic and calorimetry based approaches to characterize the mode of interaction of small molecules with DNA.Journal of fluorescence · 2013Article
- The lignan niranthin poisons Leishmania donovani topoisomerase IB and favours a Th1 immune response in mice.EMBO molecular medicine · 2012Article
Corrections and comments
- Expression of concern
Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Emergence of the bi-subunit topoisomerase I in the kinetoplastid family (Trypanosoma and Leishmania) has brought a new twist in topoisomerase research related to evolution, functional conservation and preferential sensitivities to the specific inhibitors of type IB topoisomerase family. In the present study, we describe that naturally occurring flavones baicalein, luteolin and quercetin are potent inhibitors of the recombinant Leishmania donovani topoisomerase I. These compounds bind to the free enzyme and also intercalate into the DNA at a very high concentration (300 microM) without binding to the minor grove. Here, we show that inhibition of topoisomerase I by these flavones is due to stabilization of topoisomerase I-DNA cleavage complexes, which subsequently inhibit the religation step. Their ability to stabilize the covalent topoisomerase I-DNA complex in vitro and in living cells is similar to that of the known topoisomerase I inhibitor camptothecin (CPT). However, in contrast to CPT, baicalein and luteolin failed to inhibit the religation step when the drugs were added to pre-formed enzyme substrate binary complex. This differential mechanism to induce the stabilization of cleavable complex with topoisomerase I and DNA by these selected flavones and CPT led us to investigate the effect of baicalein and luteolin on CPT-resistant mutant enzyme LdTOP1Delta39LS lacking 1-39 amino acids of the large subunit [B. B. Das, N. Sen, S. B. Dasgupta, A. Ganguly and H. K. Majumder (2005) J. Biol. Chem. 280, 16335-16344]. Baicalein and luteolin stabilize duplex oligonucleotide cleavage with LdTOP1Delta39LS. This observation was further supported by the stabilization of in vivo cleavable complex by baicalein and luteolin with highly CPT-resistant L.donovani strain. Taken together, our data suggest that the interacting amino acid residues of topoisomerase I may be partially overlapping or different for flavones and CPT. This study illuminates new properties of the flavones and provide additional insights into the ligand binding properties of L.donovani topoisomerase I.
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.