ArticleChemistry (Weinheim an der Bergstrasse, Germany)2022
Synthesis and Biological Evaluation of Flavonoid-Cinnamic Acid Amide Hybrids with Distinct Activity against Neurodegeneration in Vitro and in Vivo.
Article in Chemistry (Weinheim an der Bergstrasse, Germany), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 19 citations in OpenAlex.
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- Quercetin Hybrids and their Biological Potential.Mini reviews in medicinal chemistry · 2026Review
- Visualizing Intracellular Localization of Natural-Product-Based Chemical Probes Using Click-Correlative Light and Electron Microscopy.ACS chemical biology · 2025Article
- Bee Pollen Potential to Modulate Ferroptosis: Phytochemical Insights for Age-Related Diseases.Antioxidants (Basel, Switzerland) · 2025Review
- Cinnamic Acid Derivatives: Recent Discoveries and Development Strategies for Alzheimer's Disease.Mini reviews in medicinal chemistry · 2025Review
- Mannosamine-Engineered Nanoparticles for Precision Rifapentine Delivery to Macrophages: Advancing Targeted Therapy Against Mycobacterium Tuberculosis.Drug design, development and therapy · 2025Article
- Study ofInternational journal of molecular sciences · 2024Article
- Silibinin promotes healing in spinal cord injury through anti-ferroptotic mechanisms.JOR spine · 2024Article
- Regulation of Keap1-Nrf2 signaling in health and diseases.Molecular biology reports · 2024Review
- Hormetic Nutrition and Redox Regulation in Gut-Brain Axis Disorders.Antioxidants (Basel, Switzerland) · 2024Review
- Flavonoid-Phenolic Acid Hybrids Are Potent Inhibitors of Ferroptosis via Attenuation of Mitochondrial Impairment.Antioxidants (Basel, Switzerland) · 2023Article
- Dual-Acting Small Molecules: Subtype-Selective Cannabinoid Receptor 2 Agonist/Butyrylcholinesterase Inhibitor Hybrids Show Neuroprotection in an Alzheimer's Disease Mouse Model.Journal of medicinal chemistry · 2023Article
- Flavonoids Are Intra- and Inter-Kingdom Modulator Signals.Microorganisms · 2022Review
- Synthesis and Biological Evaluation of Flavonoid-Cinnamic Acid Amide Hybrids with Distinct Activity against Neurodegeneration in Vitro and in Vivo.Chemistry (Weinheim an der Bergstrasse, Germany) · 2022Article
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Flavonoids are polyphenolic natural products and have shown significant potential as disease-modifying agents against neurodegenerative disorders like Alzheimer's disease (AD), with activities even in vivo. Hybridization of the natural products taxifolin and silibinin with cinnamic acid led to an overadditive effect of these compounds in several phenotypic screening assays related to neurodegeneration and AD. Therefore, we have exchanged the flavonoid part of the hybrids with different flavonoids, which show higher efficacy than taxifolin or silibinin, to improve the activity of the respective hybrids. Chemical connection between the flavonoid and cinnamic acid was realized by an amide instead of a labile ester bond to improve stability towards hydrolysis. To investigate the influence of a double bond at the C-ring of the flavonoid, the dehydro analogues of the respective hybrids were also synthesized. All compounds obtained show neuroprotection against oxytosis, ferroptosis and ATP-depletion, respectively, in the murine hippocampal cell line HT22. Interestingly, the taxifolin and the quercetin derivatives are the most active compounds, whereby the quercetin derivate shows even more pronounced activity than the taxifolin one in all assays applied. As aimed for, no hydrolysis product was found in cellular uptake experiments after 4 h whereas different metabolites were detected. Furthermore, the quercetin-cinnamic acid amide showed pronounced activity in an in vivo AD mouse model at a remarkably low dose of 0.3 mg/kg.
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