Meyers Ross O, Lambert Joshua D, Hajicek Nicole, Pourpak Alan, Kalaitzis John A, Dorr Robert T
University of Arizona Cancer Center, Tucson, AZ 85724, USA.
Bioorg Med Chem Lett. 2009 Aug 15;19(16):4752-5. doi: 10.1016/j.bmcl.2009.06.063. Epub 2009 Jun 21.
Synthesis of seven semi-synthetic analogs of NDGA is described. An approach to NDGA derivatization is described in which the ortho-phenolic groups are tethered together by one atom, forming a 5-membered heterocyclic ring. The analogs were evaluated for cytotoxicity in four cancer cell lines and compared to NDGA and tetra-O-methyl-NDGA (M4N) (1a). NDGA bis-cyclic sulfate (2a), NDGA bis-cyclic carbonate (2b), and methylenedioxyphenyl-NDGA (2d) and NDGA tetra acetate (1b) showed anti-cancer activity in vitro. Two compounds, (1b) and (2b), were evaluated for anticancer activity in a mouse xenograft model of human melanoma and showed dose-dependent activity.
本文描述了七种去甲二氢愈创木酸（NDGA）半合成类似物的合成方法。文中介绍了一种NDGA衍生化方法，即邻位酚羟基通过一个原子连接在一起，形成一个五元杂环。对这些类似物在四种癌细胞系中的细胞毒性进行了评估，并与NDGA和四-O-甲基-NDGA（M4N）（1a）进行了比较。NDGA双环硫酸酯（2a）、NDGA双环碳酸酯（2b）、亚甲二氧基苯基-NDGA（2d）和NDGA四乙酸酯（1b）在体外显示出抗癌活性。两种化合物，（1b）和（2b），在人黑色素瘤小鼠异种移植模型中进行了抗癌活性评估，并显示出剂量依赖性活性。
