ArticleBritish journal of pharmacology2013
Identification through high-throughput screening of 4'-methoxyflavone and 3',4'-dimethoxyflavone as novel neuroprotective inhibitors of parthanatos.
Article in British journal of pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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
23 citing papers in PubMed, 41 citations in OpenAlex.
- Exploring the metabolic characteristics of fresh-cut sweet potatoes at different storage times based on untargeted metabolomics.Food chemistry: X · 2026Article
- Bruceine E, a natural quassinoid from Brucea javanica, inhibits PARthanatos via targeting PARP1 in ischemic stroke.Frontiers in pharmacology · 2026Article
- Anticancer Activity ofBiomolecules · 2025Article
- Investigating blood-brain barrier penetration and neurotoxicity of natural products for central nervous system drug development.Scientific reports · 2025Article
- The therapeutic potential of targeting regulated non-apoptotic cell death.Nature reviews. Drug discovery · 2023Review
- Oxidation of 3'-methoxyflavone, 4'-methoxyflavone, and 3',4'-dimethoxyflavone and their derivatives having 5,7-dihydroxyl moieties by human cytochromes P450 1B1 and 2A13.Xenobiotica; the fate of foreign compounds in biological systems · 2022Article
- PARP-1-Associated Pathological Processes: Inhibition by Natural Polyphenols.International journal of molecular sciences · 2021Review
- Potent Nrf2-inducing, antioxidant, and anti-inflammatory effects and identification of constituents validate the anti-cancer use of Uvaria chamae and Olax subscorpioidea.BMC complementary medicine and therapies · 2021Article
- PARIS farnesylation prevents neurodegeneration in models of Parkinson's disease.Science translational medicine · 2021Article
- Physiological and Pathological Factors Affecting Drug Delivery to the Brain by Nanoparticles.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Review
- Preference forXenobiotica; the fate of foreign compounds in biological systems · 2020Article
- Biotransformation of Methoxyflavones by Selected Entomopathogenic Filamentous Fungi.International journal of molecular sciences · 2020Article
- Functional Group-Dependent Induction of Astrocytogenesis and Neurogenesis by Flavone Derivatives.Biomolecules · 2019Article
- Development of Fluorogenic Substrates of α-l-Fucosidase Useful for Inhibitor Screening and Gene-expression Profiling.ACS medicinal chemistry letters · 2019Article
- Recent advances in our understanding of mast cell activation - or should it be mast cell mediator disorders?Expert review of clinical immunology · 2019Review
- Scalable Production of iPSC-Derived Human Neurons to Identify Tau-Lowering Compounds by High-Content Screening.Stem cell reports · 2017Article
- Mesenchymal stem cells protect neurons against hypoxic-ischemic injury via inhibiting parthanatos, necroptosis, and apoptosis, but not autophagy.Cellular and molecular neurobiology · 2017Article
- Molecular cloning and characterization of a flavonoid-O-methyltransferase with broad substrate specificity and regioselectivity from Citrus depressa.BMC plant biology · 2016Article
- Regulated necrosis: disease relevance and therapeutic opportunities.Nature reviews. Drug discovery · 2016Review
- Identification of Antiviral Agents Targeting Hepatitis B Virus Promoter from Extracts of Indonesian Marine Organisms by a Novel Cell-Based Screening Assay.Marine drugs · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
background and purposeThe current lack of disease-modifying therapeutics to manage neurological and neurodegenerative conditions justifies the development of more efficacious agents. One distinct pathway leading to neuronal death in these conditions and which represents a very promising and attractive therapeutic target is parthanatos, involving overactivation of PARP-1. We therefore sought to identify small molecules that could be neuroprotective by targeting the pathway. EXPERIMENTAL APPROACH: Using HeLa cells, we developed and optimized an assay for high-throughput screening of about 5120 small molecules. Structure-activity relationship (SAR) study was carried out in HeLa and SH-SY5Y cells for molecules related to the initial active compound. The neuroprotective ability of each active compound was tested in cortical neuronal cultures. KEY
results4'-Methoxyflavone (4MF) showed activity by preventing the decrease in cell viability of HeLa and SH-SY5Y cells caused by the DNA-alkylating agent, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), which induces parthanatos. A similar compound from the SAR study, 3',4'-dimethoxyflavone (DMF), also showed significant activity. Both compounds reduced the synthesis and accumulation of poly (ADP-ribose) polymer and protected cortical neurones against cell death induced by NMDA. CONCLUSIONS AND IMPLICATIONS: Our data reveal additional neuroprotective members of the flavone class of flavonoids and show that methoxylation of the parent flavone structure at position 4' confers parthanatos-inhibiting activity while additional methoxylation at position 3', reported by others to improve metabolic stability, does not destroy the activity. These molecules may therefore serve as leads for the development of novel neurotherapeutics for the management of neurological and neurodegenerative conditions.
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.