Abstract
We present here the first synthesis of organometallic complexes derived from the nonsteroidal antiandrogen nilutamide, bearing a ferrocenyl substituent at position N(1) or at C(5) of the hydantoin ring; for comparison, we also describe the C(5) p-anisyl organic analogue. All of these complexes retain a modest affinity for the androgen receptor. The N-substituted complexes show a weak or moderate antiproliferative effect (IC 50 around 68 microM) on hormone-dependent and -independent prostate cancer cells, while the C(5)-substituted compounds exhibit toxicity levels 10 times higher (IC 50 around 5.4 microM). This strong antiproliferative effect is probably due to a structural effect linked to the aromatic character of the ferrocene rather than to its organometallic feature. In addition, it seems connected to a cytotoxic effect rather than an antihormonal one. These results open the way toward a new family of molecules that are active against both hormone-dependent and hormone-independent prostate cancer cells.
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 / pharmacology*
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Anilides / chemistry
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Anilides / pharmacology
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Binding, Competitive
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Cell Proliferation / drug effects
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Crystallography, X-Ray
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Dose-Response Relationship, Drug
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Drug Screening Assays, Antitumor
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Ferrous Compounds / chemical synthesis*
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Ferrous Compounds / chemistry
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Ferrous Compounds / pharmacology*
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Humans
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Hydantoins / chemistry*
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Hydantoins / pharmacology
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Imidazolidines / chemistry*
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Imidazolidines / pharmacology
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Male
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Models, Molecular
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Molecular Structure
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Nitriles / chemistry
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Nitriles / pharmacology
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Prostatic Neoplasms / drug therapy*
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Receptors, Androgen / drug effects
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Recombinant Proteins / drug effects
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Stereoisomerism
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Structure-Activity Relationship
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Tosyl Compounds / chemistry
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Tosyl Compounds / pharmacology
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Tumor Cells, Cultured
Substances
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Androgen Antagonists
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Anilides
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Ferrous Compounds
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Hydantoins
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Imidazolidines
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Nitriles
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Receptors, Androgen
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Recombinant Proteins
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Tosyl Compounds
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nilutamide
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bicalutamide