Ocean College, Zhoushan Campus, Zhejiang University, Zhoushan, 316021, China.
College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
Sci Rep. 2017 May 10;7(1):1703. doi: 10.1038/s41598-017-01912-z.
Bioactive natural products from mangrove-derived actinomycetes are important sources for discovery of drug lead compounds. In this study, an extract prepared from culture of an actinomycete Streptomyces sp. ZQ4BG isolated from mangrove soils was found to have activity in inhibiting proliferation of glioma cells. Large culture of this mangrove actinomycete in Gause's liquid medium resulted in isolation of seven novel polyene-polyol macrolides, named as flavofungins III-IX (3-9), together with known flavofungins I (1) and II (2) and spectinabilin (10). Structures of these isolated compounds were elucidated by extensive NMR analyses and HRESIMS data. The stereochemical assignments were achieved by a combination of NOE information, universal NMR database, and chemical reactions including preparation of acetonide derivatives and Mosher esters. Flavofungins IV-VIII (4-8) are rare 32-membered polyene-polyol macrolides with a tetrahydrofuran ring, while flavofungin IX (9) represents the first example of this type of macrolide with a unique oxepane ring. Flavofungins I (1) and II (2) and spectinabilin (10) showed anti-glioma and antifungal activities.
从红树林来源的放线菌中分离得到的生物活性天然产物是发现药物先导化合物的重要来源。在本研究中,从红树林土壤中分离得到的链霉菌属放线菌 ZQ4BG 的培养物提取物被发现具有抑制神经胶质瘤细胞增殖的活性。该红树林放线菌的大量培养导致分离出了 7 种新型多烯-多元醇大环内酯,分别命名为 flavofungins III-IX(3-9),以及已知的 flavofungins I(1)和 II(2)和 spectinabilin(10)。通过广泛的 NMR 分析和 HRESIMS 数据确定了这些分离化合物的结构。通过结合 NOE 信息、通用 NMR 数据库以及包括制备缩酮衍生物和 Mosher 酯在内的化学反应,实现了立体化学分配。Flavofungins IV-VIII(4-8)是罕见的具有四氢呋喃环的 32 元多烯-多元醇大环内酯,而 flavofungin IX(9)代表了具有独特环氧丙烷环的此类大环内酯的首例。Flavofungins I(1)和 II(2)和 spectinabilin(10)表现出抗神经胶质瘤和抗真菌活性。