Electron affinity of tricyclic, bicyclic, and monocyclic compounds containing cyanoenones correlates with their potency as inducers of a cytoprotective enzyme.

Details

Serval ID
serval:BIB_3287B35784FA
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Electron affinity of tricyclic, bicyclic, and monocyclic compounds containing cyanoenones correlates with their potency as inducers of a cytoprotective enzyme.
Journal
Bioorganic & medicinal chemistry letters
Author(s)
Bensasson R.V., Dinkova-Kostova A.T., Zheng S., Saito A., Li W., Zoete V., Honda T.
ISSN
1464-3405 (Electronic)
ISSN-L
0960-894X
Publication state
Published
Issued date
01/09/2016
Peer-reviewed
Oui
Volume
26
Number
17
Pages
4345-4349
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Tricyclic, bicyclic, and monocyclic compounds containing cyanoenones induce various anti-inflammatory and cytoprotective enzymes through activation of the Keap1/Nrf2/ARE (antioxidant response element) pathway. The potency of these compounds as Nrf2 activators was determined using a prototypic cytoprotective enzyme
quinone oxidoreductase 1 (NQO1) in Hepa1c1c7 murine hepatoma cells. The electron affinity (EA) of the compounds, expressed as the energy of their lowest unoccupied molecular orbital [E (LUMO)], was evaluated using two types of quantum mechanical calculations: the semiempirical (AM1) and the density functional theory (DFT) methods. We observed striking linear correlations [r=0.897 (AM1) and 0.936 (DFT)] between NQO1 inducer potency of these compounds and their E (LUMO) regardless of the molecule size. Importantly and interestingly, this finding demonstrates that the EA is the essentially important factor that determines the reactivity of the cyanoenones with Keap1.

Keywords
Alkenes/chemistry, Animals, Cell Line, Tumor, Cyclization, Cytoprotection, Electrons, Enzyme Induction/drug effects, Kelch-Like ECH-Associated Protein 1/genetics, Kelch-Like ECH-Associated Protein 1/metabolism, Ketones/chemistry, Mice, Molecular Structure, NAD(P)H Dehydrogenase (Quinone)/metabolism, Nitriles/chemistry, Nitriles/pharmacology, Quantum Theory, Signal Transduction/drug effects, Sulfhydryl Compounds/chemistry, Sulfhydryl Compounds/pharmacology, Electron affinity, Energy of the lowest unoccupied molecular orbital, Keap1/Nrf2/ARE pathway, NAD(P)H:quinone oxidoreductase 1 (NQO1) inducer, Nrf2 activator, QSAR
Pubmed
Web of science
Create date
05/02/2018 13:48
Last modification date
21/08/2019 5:37
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