PDF(Pubmed)
Abstract：
Sea stars or starfish (class Asteroidea) and holothurians or sea cucumbers (class Holothuroidea), belonging to the phylum Echinodermata (echinoderms), are characterized by different sets of glycosidic metabolites: the steroid type in starfish and the triterpene type in holothurians. However, herein we report the isolation of eight new triterpene glycosides, pacificusosides D−K (1−3, 5−9) along with the known cucumarioside D (4), from the alcoholic extract of the Far Eastern starfish Solaster pacificus. The isolated new compounds are closely related to the metabolites of sea cucumbers, and their structures of 1−3 and 5−9 were determined by extensive NMR and ESIMS techniques. Compounds 2, 5, and 8 have a new type of tetrasaccharide chain with a terminal non-methylated monosaccharide unit. Compounds 3, 6, and 9 contain another new type of tetrasaccharide chain, having 6-O-SO3-Glc as one of the sugar units. The cytotoxic activity of 1−9 against non-cancerous mouse epidermal cells JB6 Cl41 and human melanoma cell lines SK-MEL-2, SK-MEL-28, and RPMI-7951 was determined by MTS assay. Compounds 1, 3, 4, 6, and 9 showed potent cytotoxicity against these cell lines, but the cancer selectivity (SI > 9) was observed only against the SK-MEL-2 cell line. Compounds 1, 3, 4, 6, and 9 at the non-toxic concentration of 0.1 μM significantly inhibited neoplastic cell transformation of JB6 Cl41 cells induced by chemical carcinogens (EGF, TPA) or ionizing radiation (X-rays and UVB). Moreover, compounds 1 and 4 at the non-toxic concentration of 0.1 µM possessed the highest inhibiting activity on colony formation among the investigated compounds and decreased the colonies number of SK-MEL-2 cells by 64% and 70%, respectively. Thus, triterpene glycosides 1 and 4 can be considered as prospective cancer-preventive and anticancer-compound leaders.
摘要：
海星或海星（类Asteroidea）和Holothurians或海参（类Holothuroidea），属于棘皮动物门（棘皮动物），其特征在于不同组的糖苷代谢产物：海星中的类固醇类型和四萜中的三萜类型。然而,本文报道了八种新的三萜苷的分离，太平洋皂甙D−K（1−3，5−9）以及已知的黄瓜皂甙D（4），来自远东海星Solasterpacificus的酒精提取物。分离出的新化合物与海参的代谢产物密切相关，通过广泛的NMR和ESIMS技术确定了它们的1-3和5-9结构。化合物2、5和8具有新型的四糖链,其末端具有非甲基化单糖单元。化合物3、6和9含有另一种新型的四糖链，具有6-O-SO3-Glc作为糖单元之一。通过MTS测定确定1-9对非癌小鼠表皮细胞JB6Cl41和人黑素瘤细胞系SK-MEL-2，SK-MEL-28和RPMI-7951的细胞毒性活性。化合物1、3、4、6和9对这些细胞系显示出有效的细胞毒性，但仅针对SK-MEL-2细胞系观察到癌症选择性(SI>9)。化合物1、3、4、6和9在0.1μM的无毒浓度下显着抑制化学致癌物诱导的JB6Cl41细胞的肿瘤细胞转化（EGF，TPA）或电离辐射（X射线和UVB）。此外，化合物1和4在0.1μM的无毒浓度下对集落形成的抑制活性最高，并使SK-MEL-2细胞的集落数量减少了64％和70％，分别。因此，三萜苷1和4可以被认为是前瞻性的癌症预防和抗癌化合物的领导者。
