Abstract
A series of imidazole based platinum(II) complexes were synthesised and evaluated for their cytotoxicity in HCT-116 cancer cell line, known for being partially resistant to cisplatin but sensitive to oxaliplatin. Lipophilicity was modulated by introducing differently long saturated and unsaturated chains at the N1 of the imidazole moiety. Pt-I displayed the higher cytotoxic effect achieving a IC50=38.0±14.1μM, comparable to the oxaliplatin value. The interaction between the imidazole platinum(II) complexes and the octapeptide called Mets7, the methionine-rich motif mimicking the N-terminal domain of the yCtr-1, was evaluated in order to have a major insight of the uptake and the eventual resistance mechanisms for the so-synthesised novel platinum compounds.
Keywords:
Antiproliferative compound; HCT-116; Imidzazole; Mets7; Platinum(II) complex.
Copyright © 2015 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Motifs
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / pharmacology
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Biological Transport
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Cation Transport Proteins / chemistry
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Cell Proliferation / drug effects
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Cell Survival / drug effects
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Cisplatin / pharmacology
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Coordination Complexes / chemical synthesis*
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Coordination Complexes / pharmacology
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Copper Transporter 1
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Drug Design
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Drug Resistance, Neoplasm / drug effects
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HCT116 Cells
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Humans
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Hydrophobic and Hydrophilic Interactions
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Imidazoles / chemistry*
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Inhibitory Concentration 50
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Molecular Sequence Data
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Oligopeptides / chemical synthesis
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Oligopeptides / chemistry*
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Organoplatinum Compounds / chemical synthesis*
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Organoplatinum Compounds / pharmacology
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Oxaliplatin
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Protein Structure, Tertiary
Substances
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Antineoplastic Agents
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Cation Transport Proteins
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Coordination Complexes
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Copper Transporter 1
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Imidazoles
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Oligopeptides
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Organoplatinum Compounds
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SLC31A1 protein, human
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Oxaliplatin
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imidazole
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Cisplatin