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Cyclic Cystine-Bridged Peptides from the Marine Sponge Clathria basilana Induce Apoptosis in Tumor Cells and Depolarize the Bacterial Cytoplasmic Membrane
Journal of Natural Products ( IF 3.3 ) Pub Date : 2017-11-02 00:00:00 , DOI: 10.1021/acs.jnatprod.7b00477
Amin Mokhlesi 1, 2 , Fabian Stuhldreier 3 , Katharina W. Wex 4 , Anne Berscheid 4 , Rudolf Hartmann 5 , Nidja Rehberg 1 , Parichat Sureechatchaiyan 6 , Chaidir Chaidir 7 , Matthias U. Kassack 6 , Rainer Kalscheuer 1 , Heike Brötz-Oesterhelt 4 , Sebastian Wesselborg 3 , Björn Stork 3 , Georgios Daletos 1 , Peter Proksch 1
Affiliation  

Investigation of the sponge Clathria basilana collected in Indonesia afforded five new peptides, including microcionamides C (1) and D (2), gombamides B (4), C (5), and D (6), and an unusual amide, (E)-2-amino-3-methyl-N-styrylbutanamide (7), along with 11 known compounds, among them microcionamide A (3). The structures of the new compounds were elucidated by one- and two-dimensional NMR spectroscopy as well as by high-resolution mass spectrometry. The absolute configurations of the constituent amino acid residues in 17 were determined by Marfey’s analysis. Microcionamides A, C, and D (13) showed in vitro cytotoxicity against lymphoma (Ramos) and leukemia cell lines (HL-60, Nomo-1, Jurkat J16), as well as against a human ovarian carcinoma cell line (A2780) with IC50 values ranging from 0.45 to 28 μM. Mechanistic studies showed that compounds 13 rapidly induce apoptotic cell death in Jurkat J16 and Ramos cells and that 1 and 2 potently block autophagy upon starvation conditions, thereby impairing pro-survival signaling of cancer cells. In addition, microcionamides C and A (1 and 3) inhibited bacterial growth of Staphylococcus aureus and Enterococcus faecium with minimal inhibitory concentrations between 6.2 and 12 μM. Mechanistic studies indicate dissipation of the bacterial membrane potential.

中文翻译:

海洋海绵笼草的环状胱氨酸桥肽诱导肿瘤细胞凋亡并使细菌细胞质膜去极化。

对在印度尼西亚收集的海绵笼形藻的研究发现了五种新肽,包括微杀螨酰胺C(1)和D(2),gombamides B(4),C(5)和D(6),以及一种不寻常的酰胺(E)-2-氨基-3-甲基-N-苯乙烯基丁酰胺(7),以及11种已知化合物,其中包括微硫酰胺A(3)。通过一维和二维NMR光谱以及高分辨率质谱对新化合物的结构进行了阐明。组成氨基酸残基在17中的绝对构型是由Marfey的分析确定的。Microcionamides A,C,和d(1 - 3)显示出在体外针对淋巴瘤(拉莫斯)白血病细胞系(HL-60,诺莫-1,的Jurkat J16),以及针对人类卵巢癌细胞系(A2780细胞毒性和)的IC 50值范围为0.45至28μM。机制研究表明,化合物1 - 3迅速诱导凋亡性细胞死亡在Jurkat J16和Ramos细胞和12在饥饿条件有力块自噬,从而损害癌细胞的促存活信号转导。此外,微杀虫剂C和A(13)抑制金黄色葡萄球菌粪肠球菌的细菌生长,最小抑制浓度在6.2和12μM之间。机理研究表明细菌膜电位的耗散。
更新日期:2017-11-02
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