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Garcinia Xanthones as Orally Active Antitumor Agents

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journal contribution
posted on 10.01.2013, 00:00 by Xiaojin Zhang, Xiang Li, Haopeng Sun, Xiaojian Wang, Li Zhao, Yuan Gao, Xiaorong Liu, Shenglie Zhang, Yanyan Wang, Yingrui Yang, Su Zeng, Qinglong Guo, Qidong You
Using a newly developed strategy whose key step is the regioselective propargylation of hydroxyxanthone substrates, 99 structurally diverse Garcinia natural-product-like xanthones based on gambogic acid were designed and synthesized and their in vitro antitumor activity was evaluated. A set of 40 related compounds was chosen for determination of their physicochemical properties including polar surface area, log D7.4, aqueous solubility, and permeability at pH 7.4. In the light of the in vitro antitumor activity and the physicochemical properties, two compounds were advanced into in vivo efficacy experiments. The antitumor activity of compound 112, administered po, showed more potent in vivo oral antitumor activity than gambogic acid.