Abstract
A series of six osmium(ii) complexes of the type [(η6-p-cymene)Os(C^N)X] (X = chlorido or acetato) containing benzimidazole C^N ligands with an ester group as a handle for further functionalization have been synthesized. They exhibit IC50 values in the low micromolar range in a panel of cisplatin (CDDP)-resistant cancer cells (approximately 10× more cytotoxic than CDDP in MCF-7), decrease the levels of intracellular ROS and reduce the NAD+ coenzyme, and inhibit tubulin polymerization. This discovery could open the door to a new large family of osmium(ii)-based bioconjugates with diverse modes of action.
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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Antioxidants / chemical synthesis
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Antioxidants / chemistry
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Antioxidants / 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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Chlorocebus aethiops
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Cisplatin / pharmacology
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Colchicine / pharmacology
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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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G1 Phase Cell Cycle Checkpoints / drug effects
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Humans
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Ligands
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NAD / metabolism
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Necrosis / chemically induced
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Osmium / chemistry*
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Reactive Oxygen Species / metabolism
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Tubulin Modulators / chemical synthesis
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Tubulin Modulators / chemistry
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Tubulin Modulators / pharmacology
Substances
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Antineoplastic Agents
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Antioxidants
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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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Tubulin Modulators
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NAD
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Osmium
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Cisplatin
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Colchicine