水合 Hygrocins C-G，细胞毒性萘醌类 ansamycins 来自 gdmAI 破坏链霉菌 sp.LZ35。

Hygrocins C-G, cytotoxic naphthoquinone ansamycins from gdmAI-disrupted Streptomyces sp. LZ35.

机构信息

Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University , Jinan 250012, China.

出版信息

J Nat Prod. 2013 Dec 27;76(12):2175-9. doi: 10.1021/np400474s. Epub 2013 Nov 18.

DOI:10.1021/np400474s

PMID:24490633

Abstract

Six hygrocins, polyketides of ansamycin class, were isolated from the gdmAI-disrupted Streptomyces sp. LZ35. The planar structure of hygrocins C-E (1-3) was determined by one-dimensional and two-dimensional NMR spectroscopy and high-resolution mass spectrometry. They are derivatives of hygrocin A but differ in the configuration at C-2 and the orientation of the C-3,4 double bond. Hygrocin F(4) and G(5) were shown to be isomers of hygrocin C (1) and B (6), respectively, due to the different alkyl oxygen participating in the macrolide ester linkage. Hygrocins C, D, and F were found to be toxic to human breast cancer MDA-MB-431 cells (IC50 = 0.5, 3.0, and 3.3 μM, respectively) and prostate cancer PC3 cells (IC50 = 1.9, 5.0, and 4.5 μM, respectively), while hygrocins B, E, and G were inactive.

摘要

从 gdmAI 缺失的链霉菌 sp. LZ35 中分离到六种聚酮类化合物 hygrocins，它们是 ansamycin 类的多酮化合物。通过一维和二维 NMR 光谱和高分辨率质谱确定了 hygrocins C-E（1-3）的平面结构。它们是 hygrocin A 的衍生物，但在 C-2 构型和 C-3,4 双键的取向上有所不同。Hygrocin F（4）和 G（5）分别被证明是 hygrocin C（1）和 B（6）的异构体，这是由于参与大环酯键的烷基氧不同。发现 hygrocins C、D 和 F 对人乳腺癌 MDA-MB-431 细胞（IC50 分别为 0.5、3.0 和 3.3 μM）和前列腺癌 PC3 细胞（IC50 分别为 1.9、5.0 和 4.5 μM）具有毒性，而 hygrocins B、E 和 G 则没有活性。