Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University , Columbus, Ohio 43210, United States.
J Nat Prod. 2014 Jun 27;77(6):1494-504. doi: 10.1021/np5002785. Epub 2014 Jun 12.
Two new (1 and 2) and four known arylnaphthalene lignan lactones (3-6) were isolated from different plant parts of Phyllanthus poilanei collected in Vietnam, with two further known analogues (7 and 8) being prepared from phyllanthusmin C (4). The structures of the new compounds were determined by interpretation of their spectroscopic data and by chemical methods, and the structure of phyllanthusmin D (1) was confirmed by single-crystal X-ray diffraction analysis. Several of these arylnaphthalene lignan lactones were cytotoxic toward HT-29 human colon cancer cells, with compounds 1 and 7-O-[(2,3,4-tri-O-acetyl)-α-L-arabinopyranosyl)]diphyllin (7) found to be the most potent, exhibiting IC50 values of 170 and 110 nM, respectively. Compound 1 showed activity when tested in an in vivo hollow fiber assay using HT-29 cells implanted in immunodeficient NCr nu/nu mice. Mechanistic studies showed that this compound mediated its cytotoxic effects by inducing tumor cell apoptosis through activation of caspase-3, but it did not inhibit DNA topoisomerase IIα activity.
从越南采集的 Phyllanthus poilanei 的不同植物部分中分离得到了两个新的（1 和 2）和四个已知的芳基萘木脂素内酯（3-6），并从 phyllanthusmin C（4）制备了另外两个已知类似物（7 和 8）。通过解析其光谱数据和化学方法确定了新化合物的结构，并且通过单晶 X 射线衍射分析确定了 phyllanthusmin D（1）的结构。这些芳基萘木脂素内酯中的几种对 HT-29 人结肠癌细胞具有细胞毒性，化合物 1 和 7-O-[(2,3,4-三-O-乙酰基)-α-L-阿拉伯吡喃糖基)]二菲林（7）表现出最强的活性，IC50 值分别为 170 和 110 nM。在使用植入免疫缺陷 NCr nu/nu 小鼠的 HT-29 细胞的体内中空纤维测定中，化合物 1 显示出活性。机制研究表明，该化合物通过激活 caspase-3 诱导肿瘤细胞凋亡来介导其细胞毒性作用，但它不抑制 DNA 拓扑异构酶 IIα 活性。
