三种新的单硫酸化聚羟基类固醇糖苷,香菇总皂苷A(1),B(2)、C(3)以及新的相关未硫酸化的单糖苷,香菇苷D(4),从在鄂霍次克海收集的海星Henricialeviusculaspiculifica的乙醇提取物中分离出来。化合物1-3含有两个碳水化合物部分,其中一个连接到类固醇四环核的C-3,而另一个位于苷元侧链的C-24。两个糖苷(2,3)是生物苷,和一个糖苷(1),不像他们,包括三个单糖残基。这种类型的三糖苷是一组罕见的海星极性类固醇。此外,首次在海星的类固醇糖苷中发现了5-取代的3-OSO3-α-L-Araf单元。细胞活力分析表明,1-3(浓度高达100μM)对人胚肾HEK293,黑色素瘤SK-MEL-28,乳腺癌MDA-MB-231和结肠直肠癌HCT116细胞的细胞毒性可忽略不计。这些化合物在无毒浓度下显着抑制HCT116细胞的增殖和集落形成,化合物3的效果最大。化合物3通过在G2/M期诱导剂量依赖性细胞周期停滞对HCT116细胞发挥抗增殖作用。调节细胞周期蛋白CDK2,CDK4,细胞周期蛋白D1,p21的表达和抑制蛋白激酶c-Raf的磷酸化,MEK1/2、ERK1/2的MAPK/ERK1/2通路。
Three new monosulfated polyhydroxysteroid glycosides, spiculiferosides A (1), B (2), and C (3), along with new related unsulfated monoglycoside, spiculiferoside D (4), were isolated from an ethanolic extract of the
starfish Henricia leviuscula spiculifera collected in the Sea of Okhotsk. Compounds 1-3 contain two carbohydrate moieties, one of which is attached to C-3 of the steroid tetracyclic core, whereas another is located at C-24 of the side chain of aglycon. Two glycosides (2, 3) are biosides, and one glycoside (1), unlike them, includes three monosaccharide residues. Such type triosides are a rare group of polar steroids of sea stars. In addition, the 5-substituted 3-OSO3-α-L-Araf unit was found in steroid glycosides from
starfish for the first time. Cell viability analysis showed that 1-3 (at concentrations up to 100 μM) had negligible cytotoxicity against human embryonic kidney HEK293, melanoma SK-MEL-28, breast cancer MDA-MB-231, and colorectal carcinoma HCT 116 cells. These compounds significantly inhibited proliferation and colony formation in HCT 116 cells at non-toxic concentrations, with compound 3 having the greatest effect. Compound 3 exerted anti-proliferative effects on HCT 116 cells through the induction of dose-dependent cell cycle arrest at the G2/M phase, regulation of expression of cell cycle proteins CDK2, CDK4, cyclin D1, p21, and inhibition of phosphorylation of protein kinases c-Raf, MEK1/2, ERK1/2 of the MAPK/ERK1/2 pathway.