Abstract
Gold(I) complexes with a 1,3-diethylbenzimidazol-2-ylidene N-heterocyclic carbene (NHC) ligand of the type NHC-Au-L (L=-Cl, -NHC, or -PPh3) were comparatively evaluated as thioredoxin reductase (TrxR) inhibitors and antimitochondrial anticancer agents. Different effects were noted in various biochemical assays (e.g., inhibition of TrxR, cellular and mitochondrial uptake, or effects on mitochondrial membrane potential), and this was related to properties of the complexes such as bond dissociation energies and overall charge. Remarkable antiproliferative effects, a strong induction of apoptosis, and enhancement of reactive oxygen species (ROS) formation as well as other effects on tumor cell metabolism confirmed the promising potential of the complexes as novel anticancer chemotherapeutics.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology
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Apoptosis / drug effects
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Benzimidazoles / chemical synthesis*
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Benzimidazoles / chemistry
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Benzimidazoles / pharmacology
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Coordination Complexes / chemical synthesis*
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Coordination Complexes / chemistry
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Coordination Complexes / pharmacology
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Drug Screening Assays, Antitumor
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Glutathione Peroxidase / antagonists & inhibitors
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Glutathione Reductase / antagonists & inhibitors
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Gold*
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Humans
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Ligands
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Membrane Potential, Mitochondrial / drug effects
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Mice
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Mitochondria / metabolism
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Reactive Oxygen Species / metabolism
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Structure-Activity Relationship
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Thioredoxin-Disulfide Reductase / antagonists & inhibitors
Substances
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Antineoplastic Agents
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Benzimidazoles
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Coordination Complexes
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Ligands
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Reactive Oxygen Species
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Gold
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Glutathione Peroxidase
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Glutathione Reductase
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Thioredoxin-Disulfide Reductase