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Discovery of new A- and B-type laxaphycins with synergistic anticancer activity
Bioorganic & Medicinal Chemistry ( IF 3.3 ) Pub Date : 2018-03-14 , DOI: 10.1016/j.bmc.2018.03.022
Weijing Cai 1 , Susan Matthew 2 , Qi-Yin Chen 1 , Valerie J Paul 3 , Hendrik Luesch 1
Affiliation  

Two new cyclic lipopeptides termed laxaphycins B4 (1) and A2 (2) were discovered from a collection of the marine cyanobacterium Hormothamnion enteromorphoides, along with the known compound laxaphycin A. The planar structures were solved based on a combined interpretation of 1D and 2D NMR data and mass spectral data. The absolute configurations of the subunits were determined by chiral LC-MS analysis of the hydrolysates, advanced Marfey’s analysis and 1D and 2D ROESY experiments. Consistent with similar findings on other laxaphycin A- and B-type peptides, laxaphycin B4 (1) showed antiproliferative effects against human colon cancer HCT116 cells with IC50 of 1.7 µM, while laxaphycins A and A2 (2) exhibited weak activities. The two major compounds isolated from the sample, laxaphycins A and B4, were shown to act synergistically to inhibit the growth of HCT116 colorectal cancer cells.



中文翻译:

发现具有协同抗癌活性的新型 A 型和 B 型拉沙霉素

两种新的环状脂肽,称为拉沙霉素B4 ( 1 ) 和A2 ( 2 ),是从海洋蓝细菌Hormothamnion Enteromorphoides的集合中被发现的,以及已知的化合物拉沙霉素A。基于一维和二维核磁共振的综合解释,解析了平面结构。数据和质谱数据。通过水解产物的手性 LC-MS 分析、高级 Marfey 分析以及一维和二维 ROESY 实验确定亚基的绝对构型。与其他 laxaphycin A 型和 B 型肽的类似发现一致,laxaphycin B4 ( 1 ) 对人结肠癌 HCT116 细胞显示出抗增殖作用,IC 50为 1.7 µM,而 laxaphycin A 和 A2 ( 2 ) 则表现出较弱的活性。从样品中分离出的两种主要化合物,拉沙霉素 A 和 B4,显示出协同作用,抑制 HCT116 结直肠癌细胞的生长。

更新日期:2018-03-14
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