Abstract
Incorporation of curcumin and beta-ionone into one chemical entity led to identification of a novel antiandrogen with two bulky side chains, 6, which is a pure antagonist of the wild-type and the T877A, W741C, and H874Y mutated androgen receptors (AR), showing no cross-reactivity with progesterone receptor and low micromolar cytotoxicity in LNCaP, PCa-2b, 22Rv1, and C4-2B prostate cancer cells. Molecular modeling indicates 6 adopts a "Y"-shape conformation and forms multiple hydrogen bonds with AR backbone.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Androgen Antagonists / chemical synthesis
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Androgen Antagonists / chemistry*
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Androgen Antagonists / metabolism
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Androgen Antagonists / pharmacology*
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Androgen Receptor Antagonists*
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Binding, Competitive
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Curcumin / chemistry
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Dihydrotestosterone / pharmacology
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Drug Design*
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Drug Resistance / drug effects*
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Humans
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Hydrogen Bonding
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Ligands
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Models, Molecular
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Molecular Conformation
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Mutation
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Norisoprenoids / chemistry
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Protein Structure, Tertiary
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Receptors, Androgen / chemistry
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Receptors, Androgen / genetics
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Receptors, Androgen / metabolism
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Transcriptional Activation / drug effects
Substances
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Androgen Antagonists
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Androgen Receptor Antagonists
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Ligands
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Norisoprenoids
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Receptors, Androgen
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Dihydrotestosterone
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Curcumin