Abstract
Both Topoisomerase I and angiogenesis factors have caught pharmaceutical chemists' attention in antitumor chemotherapy field. A series of indenoisoquinoline derivatives with high Top I inhibitory from our previous work were evaluated for their anti-angiogenesis property using classic in vitro and vivo models. The results demonstrated that all the compounds could significantly decrease the proliferation of endothelial cells in a concentration-dependent manner. Besides, compound 1 exerted marked inhibition of angiogenesis in vivo and in vitro models. The HIF signaling pathway in HUVECs was affected by compound 1 in a time-dependent manner. These data suggest that the tested compound 1 could serve as promising lead compound for further development and optimization.
Keywords:
Anti-angiogenesis; HIF-1α; Indenoisoquinoline derivatives.
Copyright © 2013 Elsevier Masson SAS. All rights reserved.
MeSH terms
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Angiogenesis Inhibitors / chemistry
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Angiogenesis Inhibitors / pharmacology*
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Animals
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Cell Movement / drug effects
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Cell Proliferation / drug effects
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Chickens
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Chorioallantoic Membrane / blood supply
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Chorioallantoic Membrane / drug effects
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Dose-Response Relationship, Drug
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Drug Discovery
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Human Umbilical Vein Endothelial Cells
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Humans
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Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
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Indenes / chemistry
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Indenes / pharmacology*
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Isoquinolines / chemistry
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Isoquinolines / pharmacology*
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Molecular Structure
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Neovascularization, Physiologic / drug effects*
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Rats
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Signal Transduction / drug effects
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Time Factors
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Topoisomerase I Inhibitors / chemistry
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Topoisomerase I Inhibitors / pharmacology*
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Zygote / drug effects
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Zygote / ultrastructure
Substances
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Angiogenesis Inhibitors
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HIF1A protein, human
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Hypoxia-Inducible Factor 1, alpha Subunit
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Indenes
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Isoquinolines
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Topoisomerase I Inhibitors