ArticleJournal of the American Chemical Society2014
Rational design of a structural framework with potential use to develop chemical reagents that target and modulate multiple facets of Alzheimer's disease.
Article in Journal of the American Chemical Society, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed.
- Alzheimer's Disease: From Molecular Mechanisms to Promising Therapeutic Strategies.International journal of molecular sciences · 2025Review
- Leveraging heterocycle-fused 1,4-benzoquinone to design chemical modulators for both metal-free and metal-bound amyloid-β.Chemical science · 2025Article
- Evaluation of Anti-Alzheimer's Potential of Azo-Stilbene-Thioflavin-T derived Multifunctional Molecules: Synthesis, Metal and Aβ Species Binding and Cholinesterase Activity.Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Article
- Therapeutic Potential of Ramalin Derivatives with Enhanced Stability in the Treatment of Alzheimer's Disease.Molecules (Basel, Switzerland) · 2024Article
- Targeting Biometals in Alzheimer's Disease with Metal Chelating Agents Including Coumarin Derivatives.CNS drugs · 2024Review
- Role of Metal Cations of Copper, Iron, and Aluminum and Multifunctional Ligands in Alzheimer's Disease: Experimental and Computational Insights.ACS omega · 2023Review
- Article
- Design, synthesis, and evaluation of chalcone-Vitamin E-donepezil hybrids as multi-target-directed ligands for the treatment of Alzheimer's disease.Journal of enzyme inhibition and medicinal chemistry · 2022Article
- Multipronged diagnostic and therapeutic strategies for Alzheimer's disease.Chemical science · 2022Review
- Concurrent suppression of Aβ aggregation and NLRP3 inflammasome activation for treating Alzheimer's disease.Chemical science · 2022Article
- Rational Design of a Cu Chelator That Mitigates Cu-Induced ROS Production by Amyloid Beta.Chembiochem : a European journal of chemical biology · 2022Article
- Novel hydroxybenzylamine-deoxyvasicinone hybrids as anticholinesterase therapeutics for Alzheimer's disease.Bioorganic & medicinal chemistry · 2021Article
- Redox-Active Metal Ions and Amyloid-Degrading Enzymes in Alzheimer's Disease.International journal of molecular sciences · 2021Review
- The nickel-chelator dimethylglyoxime inhibits human amyloid beta peptide in vitro aggregation.Scientific reports · 2021Article
- Amyloid Oligomers: A Joint Experimental/Computational Perspective on Alzheimer's Disease, Parkinson's Disease, Type II Diabetes, and Amyotrophic Lateral Sclerosis.Chemical reviews · 2021Review
- Different Inhibitors of Aβ42-Induced Toxicity Have Distinct Metal-Ion Dependency.ACS chemical neuroscience · 2020Article
- High-Throughput Screening at the Membrane Interface Reveals Inhibitors of Amyloid-β.Biochemistry · 2020Article
- Alleviation of symptoms of Alzheimer's disease by diminishing Aβ neurotoxicity and neuroinflammation.Chemical science · 2019Article
- The Outliers: Metal-Mediated Radical Reagents for Biological Substrate Degradation.Accounts of chemical research · 2019Article
- Recent Developments in Metal-Based Drugs and Chelating Agents for Neurodegenerative Diseases Treatments.International journal of molecular sciences · 2019Review
Corrections and comments
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Authors and funding
14 authors.
Funding
Abstract
Alzheimer's disease (AD) is characterized by multiple, intertwined pathological features, including amyloid-β (Aβ) aggregation, metal ion dyshomeostasis, and oxidative stress. We report a novel compound (ML) prototype of a rationally designed molecule obtained by integrating structural elements for Aβ aggregation control, metal chelation, reactive oxygen species (ROS) regulation, and antioxidant activity within a single molecule. Chemical, biochemical, ion mobility mass spectrometric, and NMR studies indicate that the compound ML targets metal-free and metal-bound Aβ (metal-Aβ) species, suppresses Aβ aggregation in vitro, and diminishes toxicity induced by Aβ and metal-treated Aβ in living cells. Comparison of ML to its structural moieties (i.e., 4-(dimethylamino)phenol (DAP) and (8-aminoquinolin-2-yl)methanol (1)) for reactivity with Aβ and metal-Aβ suggests the synergy of incorporating structural components for both metal chelation and Aβ interaction. Moreover, ML is water-soluble and potentially brain permeable, as well as regulates the formation and presence of free radicals. Overall, we demonstrate that a rational structure-based design strategy can generate a small molecule that can target and modulate multiple factors, providing a new tool to uncover and address AD complexity.
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