ArticleACS chemical neuroscience2014
Discovery of 5-(4-hydroxyphenyl)-3-oxo-pentanoic acid [2-(5-methoxy-1H-indol-3-yl)-ethyl]-amide as a neuroprotectant for Alzheimer's disease by hybridization of curcumin and melatonin.
Article in ACS chemical neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 73 citations in OpenAlex.
- Neuroprotective Effects of Sorghum Polyphenol in Alzheimer's Disease: In Vitro and In Silico Analyses.Nutrients · 2026Article
- Protective Activity of Melatonin Combinations and Melatonin-Based Hybrid Molecules in Neurodegenerative Diseases.Journal of pineal research · 2024Review
- Innovations in Nuclear Medicine Imaging for Reactive Oxygen Species: Applications and Radiopharmaceuticals.Antioxidants (Basel, Switzerland) · 2024Review
- Curcumin, Resveratrol and Cannabidiol as Natural Key Prototypes in Drug Design for Neuroprotective Agents.Current neuropharmacology · 2022Review
- Novel Positron Emission Tomography Radiotracers for Imaging Mitochondrial Complex I.ACS chemical neuroscience · 2021Article
- Rosmarinic Acid Potently Detoxifies Amylin Amyloid and Ameliorates Diabetic Pathology in a Transgenic Rat Model of Type 2 Diabetes.ACS pharmacology & translational science · 2021Article
- Structural understanding of 5-(4-hydroxy-phenyl)-N-(2-(5-methoxy-1H-indol-3-yl)-ethyl)-3-oxopentanamide as a neuroprotectant for Alzheimer's disease.Bioorganic & medicinal chemistry letters · 2021Article
- Curcumin as Scaffold for Drug Discovery against Neurodegenerative Diseases.Biomedicines · 2021Review
- From Hybrids to New Scaffolds: The Latest Medicinal Chemistry Goals in Multi-target Directed Ligands for Alzheimer's Disease.Current neuropharmacology · 2021Review
- Antioxidants and Neuron-Astrocyte Interplay in Brain Physiology: Melatonin, a Neighbor to Rely on.Neurochemical research · 2021Review
- Curcumin and Its Derivatives as Theranostic Agents in Alzheimer's Disease: The Implication of Nanotechnology.International journal of molecular sciences · 2020Review
- Characterization and Discovery of a Selective Small-Molecule Modulator of Mitochondrial Complex I Targeting a Unique Binding Site.Journal of medicinal chemistry · 2020Article
- Anti-fibrotic effects of curcumin and some of its analogues in the heart.Heart failure reviews · 2020Review
- Curcumin in Health and Diseases: Alzheimer's Disease and Curcumin Analogues, Derivatives, and Hybrids.International journal of molecular sciences · 2020Review
- Molecular Hybridization as a Tool in the Design of Multi-target Directed Drug Candidates for Neurodegenerative Diseases.Current neuropharmacology · 2020Review
- Development of bivalent compounds as potential neuroprotectants for Alzheimer's disease.Bioorganic & medicinal chemistry letters · 2019Article
- Role of immune-pineal axis in neurodegenerative diseases, unraveling novel hybrid dark hormone therapies.Heliyon · 2019Review
- Melatonin receptors: molecular pharmacology and signalling in the context of system bias.British journal of pharmacology · 2018Review
- Recent Advances in Neurogenic Small Molecules as Innovative Treatments for Neurodegenerative Diseases.Molecules (Basel, Switzerland) · 2016Review
- Mechanistic Insight of Bivalent Compound 21MO as Potential Neuroprotectant for Alzheimer's Disease.Molecules (Basel, Switzerland) · 2016Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
In our effort to develop effective neuroprotectants as potential treatments for Alzheimer's disease (AD), hybrid compounds of curcumin and melatonin, two natural products that have been extensively studied in various AD models, were designed, synthesized, and biologically characterized. A lead hybrid compound (7) was discovered to show significant neuroprotection with nanomolar potency (EC50 = 27.60 ± 9.4 nM) in MC65 cells, a cellular AD model. Multiple in vitro assay results established that 7 exhibited moderate inhibitory effects on the production of amyloid-β oligomers (AβOs) in MC65 cells, but not on the aggregation of Aβ species. It also exhibited significant antioxidative properties. Further mechanistic studies demonstrated that 7's antioxidant effects correlate well with its neuroprotective potency for MC65 cells, and these effects might be due to its interference with the interactions of AβOs within the mitochondria of MC65 cells. Furthermore, 7 was confirmed to cross the blood-brain barrier (BBB) and deliver a sufficient amount to brain tissue after oral administration. Collectively, these results strongly support the hybridization approach as an efficient strategy to help identify novel scaffolds with a desired pharmacology, and strongly encourage further optimization of 7 to develop more potent neuroprotectants for AD.
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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.