Synthesis and Antiangiogenic Activity of Novel Gambogic Acid Derivatives

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 <strong>4</strong>, <strong>32</strong>, <strong>35</strong>,<strong> 36</strong> 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, <strong>36</strong> was the most potent one, suggesting that it may serve as a potential new antiangiogenesis candidate with low toxicity. Additionally, <strong>36</strong> showed comparable antiproliferative activity to HUVECs and five tumor cell lines but low cytotoxicity to LO2 cells.

Keywords

• gambogic acid
• antitumor
• antiangiogenesis
• zebrafish
• toxicity