YM-254890 analogues, novel cyclic depsipeptides with Gαq/11 inhibitory activity from Chromobacterium sp QS3666
YM-254890 analogues, novel cyclic depsipeptides with Gαq/11 inhibitory activity from Chromobacterium sp QS3666
复制标题
DOI：
10.1016/j.bmc.2004.04.006
复制
发表时间：
2004-06-15
影响因子：
3.5
通讯作者：
Suzuki, K
中科院分区：
文献类型：
--
作者：
Taniguchi, M;Suzumura, K;Suzuki, K
描述了新型YM-254890（1）类似物和半合成衍生物的结构鉴定和生物活性。从产色杆菌QS 3666的发酵液中分离得到三种天然类似物YM-254891（2）、YM-254892（3）和YM-280193（4），并从YM-254890合成了两种氢化衍生物YM-385780（5）和YM-385781（6）。通过一维和二维NMR研究和质谱法确定了它们的结构。在这些化合物中，在β-HyLeu-1上具有酰基的两个天然类似物2-3和构象与1相似的一个衍生物6显示出与1相当的Galpha（q/11）抑制活性。这表明酰基β-HyLeu残基在活性中起重要作用，并且N-MeDha残基的α，β-不饱和羰基对活性不是关键的。另一个氢化衍生物5具有显著更低的活性，这可以归因于构象差异。(C)2004 Elsevier Ltd.保留所有权利。
The structure elucidation and biological activity of novel YM-254890 (1) analogues and semi-synthetic derivatives are described. Three natural analogues, YM-254891 (2), YM-254892 (3), and YM-280193 (4), were isolated from the fermentation broth of Chromobacterium sp. QS3666, and two hydrogenated derivatives, YM-385780 (5) and YM-385781 (6), were synthesized from YM-254890. Their structures were determined by one- and two-dimensional NMR studies and mass spectrometry. Among these compounds, two natural analogues 2-3 which possessed acyl groups at beta-HyLeu-1 and one derivative 6 whose conformation was similar to that of 1 showed comparable Galpha(q/11) inhibitory activity to that of 1. This indicates that the acyl beta-HyLeu residue plays an important role in activity and also that the alpha,beta-unsaturated carbonyl group of the N-MeDha residue is not critical to activity. The other hydrogenated derivative 5 had significantly less activity, which could be attributed to conformational differences. (C) 2004 Elsevier Ltd. All rights reserved.