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Biological and computational evaluation of resveratrol inhibitors against Alzheimer’s disease

journal contribution
posted on 2023-06-08, 21:37 authored by Catherine Koukoulitsa, Carolina Villalonga-Barber, Robert Csonka, Xanthippi Alexi, Georgios Leonis, Dimitris Dellis, Elizabeth Hamelink, Oscar Belda, Barry R Steele, Maria Micha-Screttas, Michael N Alexis, Manthos G Papadopoulos, Thomas Mavromoustakos
It has been reported that beta amyloid induces production of radical oxygen species and oxidative stress in neuronal cells, which in turn upregulates ß-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.

History

Publication status

  • Published

File Version

  • Published version

Journal

Journal of Enzyme Inhibition and Medicinal Chemistry

ISSN

1475-6366

Publisher

Informa Healthcare

Issue

1

Volume

31

Page range

67-77

Department affiliated with

  • Chemistry Publications

Full text available

  • No

Peer reviewed?

  • Yes

Legacy Posted Date

2015-07-14

First Compliant Deposit (FCD) Date

2015-07-14

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