Abstract
This paper reports the synthesis of a series of evodiamine derivatives. We assayed the ability to inhibit cell growth on three human tumour cell lines (H460, MCF-7 and HepG2) and we evaluated the capacity to interfere with the catalytic activity of topoisomerase I both by the relaxation assay and the occurrence of the cleavable complex. Moreover, whose effect on sirtuins 1, 2 and 3 was investigated. Finally, molecular docking analyses were performed in an attempt to rationalize the biological results.
Keywords:
Evodiamine; Quinazolinecarboline alkaloids; Sirtuins; Topoisomerase I; enantiomer; ent; epi; epimer.
Copyright © 2013 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alkaloids / chemistry
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Binding Sites
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Carbolines / chemistry
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Cell Line, Tumor
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Cell Proliferation / drug effects
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DNA Topoisomerases, Type I / chemistry*
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DNA Topoisomerases, Type I / metabolism
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Enzyme Activation / drug effects
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Hep G2 Cells
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Humans
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MCF-7 Cells
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Molecular Docking Simulation
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Protein Structure, Tertiary
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Quinazolines / chemical synthesis
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Quinazolines / chemistry*
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Quinazolines / pharmacology
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Sirtuins / antagonists & inhibitors*
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Sirtuins / metabolism
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Topoisomerase I Inhibitors / chemical synthesis
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Topoisomerase I Inhibitors / chemistry*
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Topoisomerase I Inhibitors / pharmacology
Substances
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Alkaloids
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Carbolines
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Quinazolines
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Topoisomerase I Inhibitors
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evodiamine
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Sirtuins
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DNA Topoisomerases, Type I
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TOP1 protein, human