Abstract
The synthesis and the biological evaluation of a new ferrocenyl-iminosugar conjugate designed for fucosidase inhibitory and anticancer activity is described. The compound showed strong affinity for fucosidase from bovine kidney (Ki=23 nM) and from Bacteroides thetaiotaomicron (Ki=150 nM), displaying a 10-fold tighter binding affinity for these enzymes than the previous analogs. The interaction pattern that improves binding has been evaluated through structural analysis of the inhibitor-enzyme complex. The ferrocenyl-iminosugar exhibits significant anticancer activity on MDA-MB-231 and SK-MEL28 cell lines at 100 μM.
Keywords:
Anticancer; Ferrocene; Fucosidase; Iminosugars; Inhibitors.
Copyright © 2016 Elsevier Ltd. All rights reserved.
Publication types
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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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Bacteroides / enzymology
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Binding Sites / drug effects
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Cattle
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Cell Survival / drug effects
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Dose-Response Relationship, Drug
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Drug Screening Assays, Antitumor
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology*
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Ferrous Compounds / chemistry
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Ferrous Compounds / pharmacology*
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Humans
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Imino Sugars / chemistry
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Imino Sugars / pharmacology*
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Kidney / enzymology
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Metallocenes
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Molecular Structure
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Structure-Activity Relationship
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alpha-L-Fucosidase / antagonists & inhibitors*
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alpha-L-Fucosidase / metabolism
Substances
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Antineoplastic Agents
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Enzyme Inhibitors
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Ferrous Compounds
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Imino Sugars
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Metallocenes
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alpha-L-Fucosidase
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ferrocene