- Aurones as histone deacetylase inhibitors: Identification of key features
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In this study, a total of 22 flavonoids were tested for their HDAC inhibitory activity using fluorimetric and BRET-based assays. Four aurones were found to be active in both assays and showed IC50 values below 20 μM in the enzymatic assay. Molecular modelling revealed that the presence of hydroxyl groups was responsible for good compound orientation within the isoenzyme catalytic site and zinc chelation.
- Zwick, Vincent,Chatzivasileiou, Alkiviadis-Orfefs,Deschamps, Nathalie,Roussaki, Marina,Simes-Pires, Claudia A.,Nurisso, Alessandra,Denis, Iza,Blanquart, Christophe,Martinet, Nadine,Carrupt, Pierre-Alain,Detsi, Anastasia,Cuendet, Muriel
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supporting information
p. 5497 - 5501
(2014/12/12)
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- Functionalized aurones as inducers of NAD(P)H:quinone oxidoreductase 1 that activate AhR/XRE and Nrf2/ARE signaling pathways: Synthesis, evaluation and SAR
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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.
- Lee, Chong-Yew,Chew, Eng-Hui,Go, Mei-Lin
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experimental part
p. 2957 - 2971
(2010/09/03)
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- Natural and synthetic 2′-hydroxy-chalcones and aurones: Synthesis, characterization and evaluation of the antioxidant and soybean lipoxygenase inhibitory activity
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A series of 2′-hydroxy-chalcones and their oxidative cyclization products, aurones, have been synthesized and tested for their antioxidant and lipoxygenase inhibitory activity. The natural product aureusidin (31) was synthesized in high yield by a new approach. An extensive structure-relationship study was performed and revealed that several chalcones and aurones possess an appealing pharmacological profile combining high antioxidant and lipid peroxidation activity with potent soybean LOX inhibition.
- Detsi, Anastasia,Majdalani, Maya,Kontogiorgis, Christos A.,Hadjipavlou-Litina, Dimitra,Kefalas, Panagiotis
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experimental part
p. 8073 - 8085
(2010/03/24)
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- Dimethoxyaurones: Potent inhibitors of ABCG2 (breast cancer resistance protein)
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A series of 4,6-dimethoxyaurones were synthesized by reacting 4,6-dimethoxybenzofuran-3(2H)-one with various benzaldehydes in a base-catalyzed aldol reaction. A Z configuration was assigned to the aurones based on spectroscopic and crystallographic data.
- Sim, Hong-May,Lee, Chong-Yew,Ee, Pui Lai Rachel,Go, Mei-Lin
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p. 293 - 306
(2008/12/23)
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