Cited by 37Alzheimer's disease research and treatmentsCholinesterase and Neurodegenerative DiseasesComputational Drug Discovery Methods

Biological and Computational Evaluation of Resveratrol Inhibitors against Alzheimer's Disease

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Koukoulitsa, Catherine, Villalonga-Barber, Caroline, Csonka, Robert, Alexi, Xanthippi, Leonis, Georgios, Dellis, Dimitris, Hamelink, Elizabeth, Belda, Oscar +5 more·2016·Journal of Enzyme Inhibition and Medicinal Chemistry

Abstract

It has been reported that beta amyloid induces production of radical oxygen species and oxidative stress in neuronal cells, which in turn upregulates β-secretase (BACE-1) expression and beta amyloid levels, thereby propagating oxidative stress and increasing neuronal injury. A series of resveratrol derivatives, known to be inhibitors of oxidative stress-induced neuronal cell death (oxytosis) were biologically evaluated against BACE-1 using homogeneous time-resolved fluorescence (TRF) assay. Correlation between oxytosis inhibitory and BACE-1 inhibitory activity of resveratrol derivatives was statistically significant, supporting the notion that BACE-1 may act as pivotal mediator of neuronal cell oxytosis. Four of the biologically evaluated resveratrol analogs demonstrated considerably higher activity than resveratrol in either assay. The discovery of some "hits" led us to initiate detailed docking studies associated with Molecular Dynamics in order to provide a plausible explanation for the experimental results and understand their molecular basis of action.

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  1. Olsson MHM, Søndergard CR, Rostkowski M, Jensen JH. PROPKA3: consistent treatment of internal and surface residues in empirical pKa predictions. J Chem Theory Comput 2011;7:525-37.
  2. Wang J, Wolf RM, Caldwell JW, et al. Development and testing of a general Amber forcefield. J Comput Chem 2004;25:1157-74.
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Authors
Koukoulitsa, C., Villalonga-Barber, C., Csonka, R., Alexi, X., Leonis, G., Dellis, D., Hamelink, E., Belda, O., Steele, B. R., Micha-Screttas, M., Alexis, M. N., Papadopoulos, M. G., & Mavromoustakos, T.
Affiliations
  • National and Kapodistrian University of Athens (GR)
  • National Hellenic Research Foundation (GR)
  • Institute of Accelerating Systems and Applications (GR)
  • Medivir (Sweden) (SE)
Corresponding author
  • Koukoulitsa, Catherine
  • Mavromoustakos, Thomas
Venue
Journal of Enzyme Inhibition and Medicinal Chemistry
Published
2015-07-06
Volume
31
Issue
1
Pages
67-77
ISSN
  • 1475-6366 (ISSN-L)
  • 1475-6374
OpenAlex
W1884115466
Cited by
37
References
69
Citations by year
2025: 3 · 2023: 2 · 2022: 6 · 2021: 8 · 2020: 4 · 2019: 4 · 2018: 2 · 2017: 5 · 2016: 3
FWCI
2.45
Type
journal article
Language
en
Open access
Locations
  • Journal of Enzyme Inhibition and Medicinal Chemistry (publishedVersion)
  • PubMed (publishedVersion)
  • Sussex Research Online (University of Sussex) (submittedVersion)
  • Figshare (submittedVersion, cc-by)
  • National Hellenic Research Foundation Helios Repository (National Hellenic Research Foundation) (submittedVersion)
Funders
  • European Commission
  • Università degli Studi di Perugia
  • Serbian Academy of Sciences and Arts
  • European Social Fund
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
  • Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
Keywords
resveratrol derivatives, Alzheimer's disease, amyloid-beta, BACE1, beta-secretase inhibition, oxytosis, oxidative stress, neuronal cell death, resveratrol analogues, molecular docking, molecular dynamics simulation
MeSH terms
Resveratrol, Alzheimer Disease, Animals, Cell Line, Dose-Response Relationship, Drug, Neurons, Stilbenes, Structure-Activity Relationship, Molecular Structure, Aspartic Acid Endopeptidases, Cell Death, Oxidative Stress, Mice, Amyloid Precursor Protein Secretases, Molecular Dynamics Simulation

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