Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, Center for Biostatistics, The Ohio State University, Columbus, Ohio 43210, United States.
J Nat Prod. 2011 Oct 28;74(10):2193-9. doi: 10.1021/np200557e. Epub 2011 Oct 5.
Bioassay-guided fractionation was conducted on a chloroform-soluble extract of the aerial parts of Piper sarmentosum collected in Vietnam, monitored by a mitochondrial transmembrane potential assay using HT-29 human colon cancer cells. This led to the isolation of four new C-benzylated dihydroflavones, sarmentosumins A-D (1-4), as well as 14 known compounds. The structures of the new compounds were elucidated on the basis of spectroscopic data interpretation. Among these compounds, 1-4 as well as five known C-benzylated dihydroflavones (5-9) and a piperamide, pipercallosine (11), were found to induce apoptosis in HT-29 cells by moderately reducing the mitochondrial transmembrane potential (ΔΨm), with ED50 values ranging from 1.6 to 13.6 μM. Furthermore, 7-methoxydichamanetin (8) and pinocembrin (10) exhibited proteasome inhibitory activities in a human 20S proteasome bioassay with IC50 values of 3.45±0.18 and 2.87±0.26 μM, respectively. This is the first time that C-benzylated dihydroflavones have been reported to demonstrate an apoptotic effect associated with disruption of the mitochondrial transmembrane potential.
生物测定指导的分馏是在越南采集的 Piper sarmentosum 地上部分的氯仿可溶提取物上进行的，使用 HT-29 人结肠癌细胞的线粒体跨膜电位测定进行监测。这导致了四个新的 C-苄基二氢黄酮，sarmentosumins A-D（1-4）的分离，以及 14 种已知化合物。根据光谱数据解释，确定了新化合物的结构。在这些化合物中，1-4 以及五种已知的 C-苄基二氢黄酮（5-9）和一种哌酰胺，pipercallosine（11）被发现通过适度降低线粒体跨膜电位（ΔΨm）诱导 HT-29 细胞凋亡，ED50 值范围为 1.6 至 13.6 μM。此外，7-甲氧基二氢桑辛素（8）和 pinocembrin（10）在人 20S 蛋白酶体生物测定中表现出蛋白酶体抑制活性，IC50 值分别为 3.45±0.18 和 2.87±0.26 μM。这是首次报道 C-苄基二氢黄酮具有与线粒体跨膜电位破坏相关的凋亡作用。
