ArticlePharmaceutical research2017
Why Have Clinical Trials of Antioxidants to Prevent Neurodegeneration Failed? - A Cellular Investigation of Novel Phenothiazine-Type Antioxidants Reveals Competing Objectives for Pharmaceutical Neuroprotection.
Article in Pharmaceutical research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
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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.
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Who cites it
13 citing papers in PubMed, 24 citations in OpenAlex.
- Exploring the Interplay of Antioxidants, Inflammation, and Oxidative Stress: Mechanisms, Therapeutic Potential, and Clinical Implications.Diseases (Basel, Switzerland) · 2025Review
- 2-Aminomethyl phenothiazine, its alkyl and triphenylphosphonium derivatives suppress erastin-induced ferroptosis in BT-474 cells but exhibit distinct cytotoxic activities.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Prolactin protects hippocampal neurons against H2O2-induced neurotoxicity by suppressing BAX and NOX4 via the NF-κB signaling pathway.PloS one · 2024Article
- Functionalization of Morin-Loaded PLGA Nanoparticles with Phenylalanine Dipeptide Targeting the Brain.Pharmaceutics · 2022Article
- Cannabidiol modulation of oxidative stress and signalling.Neuronal signaling · 2021Review
- Article
- Dietary Antioxidants and the Mitochondrial Quality Control: Their Potential Roles in Parkinson's Disease Treatment.Antioxidants (Basel, Switzerland) · 2020Review
- Repositioning Natural Antioxidants for Therapeutic Applications in Tissue Engineering.Bioengineering (Basel, Switzerland) · 2020Review
- NChemical biology & drug design · 2019Article
- Therapeutic Applications of Cysteamine and Cystamine in Neurodegenerative and Neuropsychiatric Diseases.Frontiers in neurology · 2019Review
- Neuroprotection through flavonoid: Enhancement of the glyoxalase pathway.Redox biology · 2018Review
- Neuroprotective Natural Molecules, From Food to Brain.Frontiers in neuroscience · 2018Review
- Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeOnly a fraction of the currently established low-molecular weight antioxidants exhibit cytoprotective activity in living cells, which is considered a prerequisite for their potential clinical usefulness in Parkinson's disease or stroke. Post hoc structure-activity relationship analyses have predicted that increased lipophilicity and enhanced radical stabilization could contribute to such cytoprotective activity.
methodsWe have synthesized a series of novel phenothiazine-type antioxidants exhibiting systematic variation in their lipophilicity and radical stabilization. Phenothiazine was chosen as lead structure for its superior activity at baseline. The novel compounds were evaluated for their neuroprotective potency in cell culture, and for their primary molecular targets.
resultsLipophilicity was associated with enhanced cytoprotective activity, but only to a certain threshold (logP ≈ 7). Benzannulation likewise produced improved cytoprotectants that exhibited very low EC
conclusionsLipophilicity, radical stabilization and molecular weight appear to form an uneasy triangle, in which a slightly faulty selection may readily abolish neuroprotective activity.
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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.