Abstract
A D-ring contracted analogue of the strongly cytotoxic marine pyrrole alkaloid lamellarin D was synthesized and investigated for its antiproliferative action towards a wild type and a multidrug resistant (MDR) cancer cell line. The compound was found to inhibit tumor cell growth at submicromolar concentrations and showed a lower relative resistance in the MDR cell line than the antitumor drug camptothecin to which lamellarin D shows cross resistance and with which lamellarin D shares the same binding site.
Keywords:
Alkaloid synthesis; Antitumor activity; Molecular docking; Natural product mimetics; Transition metal catalysis.
Copyright © 2017 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents / chemical synthesis
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Antineoplastic Agents / metabolism
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Antineoplastic Agents / pharmacology
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Binding Sites
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Cell Line, Tumor
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Cell Survival / drug effects
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Coumarins / chemical synthesis*
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Coumarins / metabolism
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Coumarins / pharmacology*
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DNA Topoisomerases, Type I / chemistry
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DNA Topoisomerases, Type I / genetics
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DNA Topoisomerases, Type I / metabolism
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Drug Resistance, Neoplasm / drug effects
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G2 Phase Cell Cycle Checkpoints / drug effects
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Heterocyclic Compounds, 4 or More Rings / chemical synthesis*
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Heterocyclic Compounds, 4 or More Rings / metabolism
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Heterocyclic Compounds, 4 or More Rings / pharmacology*
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Humans
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Isoquinolines / chemical synthesis*
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Isoquinolines / metabolism
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Isoquinolines / pharmacology*
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M Phase Cell Cycle Checkpoints / drug effects
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Molecular Docking Simulation
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Mutagenesis
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Protein Structure, Tertiary
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Topoisomerase I Inhibitors / chemical synthesis*
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Topoisomerase I Inhibitors / metabolism
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Topoisomerase I Inhibitors / pharmacology
Substances
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Antineoplastic Agents
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Coumarins
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Heterocyclic Compounds, 4 or More Rings
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Isoquinolines
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Topoisomerase I Inhibitors
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lamellarin D
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DNA Topoisomerases, Type I