Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.ejmech.2010.03.023
Title: Functionalized aurones as inducers of NAD(P)H:quinone oxidoreductase 1 that activate AhR/XRE and Nrf2/ARE signaling pathways: Synthesis, evaluation and SAR
Authors: Lee, C.-Y. 
Chew, E.-H. 
Go, M.-L. 
Keywords: Aurones
Chemoprevention
NAD(P)H:quinone oxidoreductase 1
Phase II enzyme inducers
Issue Date: Jul-2010
Citation: Lee, C.-Y., Chew, E.-H., Go, M.-L. (2010-07). Functionalized aurones as inducers of NAD(P)H:quinone oxidoreductase 1 that activate AhR/XRE and Nrf2/ARE signaling pathways: Synthesis, evaluation and SAR. European Journal of Medicinal Chemistry 45 (7) : 2957-2971. ScholarBank@NUS Repository. https://doi.org/10.1016/j.ejmech.2010.03.023
Abstract: The chemopreventive potential of functionalized aurones and related compounds as inducers of NAD(P)H:quinone oxidoreductase 1 (NQO1, EC 1.6.99.2) are described. Several 4,6-dimethoxy and 5-hydroxyaurones induced NQO1 activity of Hepa1c1c7 cells by 2-fold at submicromolar concentrations, making these the most potent inducers to be identified from this class. Mechanistically, induction of NQO1 was mediated by the activation of AhR/XRE and Nrf2/ARE pathways, indicating that aurones may be mixed activators of NQO1 induction or agents capable of exploiting the proposed cross-talk between the AhR and Nrf2 gene batteries. QSAR analysis by partial least squares projection to latent structures (PLS) identified size parameters, in particular those associated with non-polar surface areas, as an important determinant of induction activity. These were largely determined by the substitution on rings A and B. A stereoelectronic role for the exocyclic double bond as reflected in the E LUMO term was also identified. The electrophilicity of the double bond or its effect on the conformation of the target compound are possible key features for induction activity. © 2010 Elsevier Masson SAS.
Source Title: European Journal of Medicinal Chemistry
URI: http://scholarbank.nus.edu.sg/handle/10635/105973
ISSN: 02235234
DOI: 10.1016/j.ejmech.2010.03.023
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