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Structures and Activities of Tiahuramides A–C, Cyclic Depsipeptides from a Tahitian Collection of the Marine Cyanobacterium Lyngbya majuscula
Journal of Natural Products ( IF 5.1 ) Pub Date : 2018-05-24 00:00:00 , DOI: 10.1021/acs.jnatprod.7b00751
Annabel Levert 1 , Rebeca Alvariño 2 , Louis Bornancin 1 , Eliane Abou Mansour 1 , Adam M. Burja 3 , Anne-Marie Genevière 4 , Isabelle Bonnard 1, 5 , Eva Alonso 2 , Luis Botana 2 , Bernard Banaigs 1, 5
Affiliation  

The structures of three new cyclic depsipeptides, tiahuramides A (1), B (2), and C (3), from a French Polynesian collection of the marine cyanobacterium Lyngbya majuscula are described. The planar structures of these compounds were established by a combination of mass spectrometry and 1D and 2D NMR experiments. Absolute configurations of natural and nonproteinogenic amino acids were determined through a combination of acid hydrolysis, derivitization with Marfey’s reagent, and HPLC. The absolute configuration of hydroxy acids was confirmed by Mosher’s method. The antibacterial activities of tiahuramides against three marine bacteria were evaluated. Compound 3 was the most active compound of the series, with an MIC of 6.7 μM on one of the three tested bacteria. The three peptides inhibit the first cell division of sea urchin fertilized eggs with IC50 values in the range from 3.9 to 11 μM. Tiahuramide B (2), the most potent compound, causes cellular alteration characteristics of apoptotic cells, blebbing, DNA condensation, and fragmentation, already at the first egg cleavage. The cytotoxic activity of compounds 13 was tested in SH-SY5Y human neuroblastoma cells. Compounds 2 and 3 showed an IC50 of 14 and 6.0 μM, respectively, whereas compound 1 displayed no toxicity in this cell line at 100 μM. To determine the type of cell death induced by tiahuramide C (3), SH-SY5Y cells were costained with annexin V–FITC and propidium iodide and analyzed by flow cytometry. The double staining indicated that the cytotoxicity of compound 3 in this cell line is produced by necrosis.

中文翻译:

ia虫酰胺AC的结构和活性,来自海洋蓝藻Lyngbya majuscula大溪地馆藏的环状二

描述了来自法国波利尼西亚海洋蓝藻Lyngbya majuscula集合的三个新的环状二肽肽,噻呋酰胺A(1),B(2)和C(3)的结构。这些化合物的平面结构是通过质谱以及1D和2D NMR实验的组合而建立的。天然和非蛋白质氨基酸的绝对构型是通过酸水解,用Marfey试剂衍生化和HPLC的组合来确定的。羟基酸的绝对构型通过Mosher方法得到证实。评价了噻呋酰胺对三种海洋细菌的抗菌活性。化合物3是该系列中活性最高的化合物,对三种被测细菌之一的MIC为6.7μM。这三种肽抑制海胆受精卵的首次细胞分裂,IC 50值在3.9至11μM的范围内。最有效的化合物Tiahuramide B(2)会在第一次卵裂时引起凋亡细胞的细胞改变,起泡,DNA浓缩和断裂。化合物的细胞毒性活性1 - 3中的SH-SY5Y成神经细胞瘤的人类细胞进行了测试。化合物23的IC 50分别为14和6.0μM,而化合物1在此细胞系中100μM时无毒性。为了确定由噻草酰胺C(3)诱导的细胞死亡类型,将SH-SY5Y细胞与膜联蛋白V–FITC和碘化丙啶共染色,并通过流式细胞仪进行分析。双重染色表明化合物3在该细胞系中的细胞毒性是由坏死产生的。
更新日期:2018-05-24
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