Τίτλος:
Biological and computational evaluation of resveratrol inhibitors against Alzheimer’s disease
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
It has been reported that beta amyloid induces production of radical oxygen species and
oxidative stress in neuronal cells, which in turn upregulates b-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 timeresolved 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.
Συγγραφείς:
C. Koukoulitsa, C.V.Barber, R, Csonka, X. Alexi, G. Leonis, D. Dellis, E. Hamelink, O. Belda, B.R. Steele, M.M.Screttas, M. N. Alexis, M. G. Papadopoulos, T. Mavromoustakos
Περιοδικό:
Journal of Enzyme Inhibition and Medicinal Chemistry
Εκδότης:
Informa Healthcare
Λέξεις-κλειδιά:
Alzheimer’s disease, BACE-1, docking, free energy calculations, MM–PBSA, molecular dynamics, resveratrol analogs
Κύρια θεματική κατηγορία:
Θετικές Επιστήμες
DOI:
10.3109/14756366.2014.1003928
Αρχείο:
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koukoulitsa2016.pdf
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