Potent Cytotoxic Arylnaphthalene Lignan Lactones from Phyllanthus poilanei
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- 作者：Yulin Ren ; Daniel D. Lantvit ; Youcai Deng ; Ragu Kanagasabai ; Judith C. Gallucci ; Tran Ngoc Ninh ; Hee-Byung Chai ; Djaja D. Soejarto ; James R. Fuchs ; Jack C. Yalowich ; Jianhua Yu ; Steven M. Swanson ; A. Douglas Kinghorn
- 刊名：Journal of Natural Products
- 出版年：2014
- 出版时间：June 27, 2014
- 年：2014
- 卷：77
- 期：6
- 页码：1494-1504
- 全文大小：603K
- ISSN：1520-6025
文摘
Two new (1 and 2) and four known arylnaphthalene lignan lactones (3鈥?b>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)-伪-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 II伪 activity.