Abstract
Gambogic acid (GA) is in a phase II clinical trial as an antitumor and antiangiogenesis agent. In this study, 36 GA derivatives were synthesized and screened in a zebrafish model to evaluate their antiangiogenic activity and toxicity. Derivatives 4, 32, 35, 36 effectively suppressed the formation of newly grown blood vessels and showed lower toxicities than GA as evaluated by zebrafish heart rates and mortalities. They also exhibited more potent migration and HUVEC tube formation inhibiting activities than GA. Among them, 36 was the most potent one, suggesting that it may serve as a potential new antiangiogenesis candidate with low toxicity. Additionally, 36 showed comparable antiproliferative activity to HUVECs and five tumor cell lines but low cytotoxicity to LO2 cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Angiogenesis Inhibitors / chemical synthesis*
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Angiogenesis Inhibitors / chemistry
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Angiogenesis Inhibitors / pharmacology*
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Animals
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Animals, Genetically Modified
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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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Cell Line, Tumor
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Cell Movement / drug effects
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Cell Proliferation / drug effects
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Embryo, Nonmammalian / drug effects
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Heart Rate / drug effects
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Human Umbilical Vein Endothelial Cells / drug effects
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Human Umbilical Vein Endothelial Cells / metabolism
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Humans
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Inhibitory Concentration 50
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Neovascularization, Physiologic / drug effects
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Structure-Activity Relationship
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Xanthones / chemical synthesis*
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Xanthones / chemistry
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Xanthones / pharmacology*
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Zebrafish
Substances
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Angiogenesis Inhibitors
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Antineoplastic Agents
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Xanthones
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gambogic acid