State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
J Med Chem. 2013 Jan 10;56(1):276-92. doi: 10.1021/jm301593r. Epub 2012 Dec 31.
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.
采用一种新开发的策略，其关键步骤是对羟基黄烷酮底物进行区域选择性炔丙基化，设计和合成了 99 种结构多样的基于藤黄酸的藤黄天然产物类似物黄烷酮，并评估了它们的体外抗肿瘤活性。选择了一组 40 种相关化合物来确定它们的物理化学性质，包括极性表面积、log D₇.₄、水溶解度和在 pH 7.4 时的渗透性。根据体外抗肿瘤活性和物理化学性质，两种化合物被推进到体内疗效实验中。化合物 112 的口服抗肿瘤活性显示出比藤黄酸更强的体内口服抗肿瘤活性。
