Abstract
A series of azaisoflavone analogs were designed and synthesized and their transactivation activities and binding affinities for ERα and ERβ were investigated. Among these compounds, 2b and 3a were the most potent with 6.5 and 1.1 μM of EC50, respectively. Molecular modeling study showed putative binding modes of the compound 3a in the active site of ERα and ERβ, which were similar with that of genistein and provided insight of the effect of N-alkyl substitution of azaisoflavones on ERβ activity. Also, a biphasic effect of azaisoflavone analogs on MCF-7 cell growth depending on their concentrations was investigated.
Keywords:
Azaisoflavones; ER agonist; Estrogen receptor; Proliferation.
Copyright © 2014 Elsevier Masson SAS. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Catalytic Domain
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Cell Proliferation / drug effects
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Chemistry Techniques, Synthetic
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Dose-Response Relationship, Drug
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Drug Design*
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Estrogen Receptor alpha / chemistry
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Estrogen Receptor alpha / genetics
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Estrogen Receptor alpha / metabolism
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Estrogen Receptor beta / chemistry
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Estrogen Receptor beta / genetics
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Estrogen Receptor beta / metabolism
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Flavones / chemical synthesis*
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Flavones / chemistry
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Flavones / metabolism
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Flavones / pharmacology*
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Humans
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MCF-7 Cells
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Molecular Docking Simulation
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Phytoestrogens / chemical synthesis*
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Phytoestrogens / chemistry
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Phytoestrogens / metabolism
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Phytoestrogens / pharmacology*
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Quinolones / chemical synthesis*
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Quinolones / chemistry
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Quinolones / metabolism
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Quinolones / pharmacology*
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Structure-Activity Relationship
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Transcriptional Activation / drug effects
Substances
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Estrogen Receptor alpha
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Estrogen Receptor beta
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Flavones
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Phytoestrogens
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Quinolones