Ocean College, Zhoushan Campus, Zhejiang University, Zhoushan, 316021, China.
College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
Sci Rep. 2018 Jan 8;8(1):72. doi: 10.1038/s41598-017-18484-7.
Marine natural products are important resources for discovering novel anticancer drugs. In this study, an extract prepared from the culture of a sea anemone-derived actinomycete Streptomyces sp. ZZ406 in soluble starch and casein-related liquid medium was found to have activity in inhibiting the proliferation of glioma cells and reducing the production of lactate in glioma cells. Chemical investigation of this active crude extract resulted in the isolation of four new compounds and seven known ones. Structures of the new compounds were determined by a combination of extensive NMR analyses, HRESIMS and MS-MS data, electronic circular dichroism calculation, chemical degradation, and Marfey's method. New compound 1 showed potent activity against the proliferation of different glioma cells with IC values of 4.7 to 8.1 μM, high selectivity index (>12.3 to 21.3), and good stability in human liver microsomes. Western blot analysis revealed that compound 1 remarkably downregulated the expressions of several important glioma glycolytic enzymes. The data from this study suggested that compound 1 might have potential as a novel anti-glioma agent to be further investigated.
海洋天然产物是发现新型抗癌药物的重要资源。在这项研究中，从海葵衍生放线菌链霉菌 sp. ZZ406 在可溶性淀粉和酪蛋白相关液体培养基中的培养物中制备的提取物被发现具有抑制神经胶质瘤细胞增殖和减少神经胶质瘤细胞中乳酸产量的活性。对这种活性粗提取物的化学研究导致分离出了四个新化合物和七个已知化合物。新化合物的结构通过广泛的 NMR 分析、HRESIMS 和 MS-MS 数据、电子圆二色性计算、化学降解和 Marfey 法的组合来确定。新化合物 1 对不同神经胶质瘤细胞的增殖表现出很强的活性，IC 值为 4.7 至 8.1 μM，高选择性指数（>12.3 至 21.3），在人肝微粒体中稳定性良好。Western blot 分析表明，化合物 1 显著下调了几种重要的神经胶质瘤糖酵解酶的表达。这项研究的数据表明，化合物 1 可能具有作为新型抗神经胶质瘤药物的潜力，值得进一步研究。
