Applying Molecular Networking for the Detection of Natural Sources and Analogues of the Selective Gq Protein Inhibitor FR900359

文献类型： 外文期刊

第一作者： Reher, Raphael

作者： Reher, Raphael;Kehraus, Stefan;Koenig, Gabriele M.;Cruesemann, Max;Heycke, Nina;Annala, Suvi;Kostenis, Evi;Kuschak, Markus;Mueller, Christa E.;Dai, Hao-Fu

作者机构：

期刊名称：JOURNAL OF NATURAL PRODUCTS （ 影响因子：4.05； 五年影响因子：4.603 ）

ISSN： 0163-3864

年卷期： 2018 年 81 卷 7 期

页码：

收录情况： SCI

摘要： The cyclic depsipeptide FR900359 (FR), isolated from the traditional Chinese medicine plant Ardisia crenata, is a potent Gq protein inhibitor and thus a valuable tool to study Gq-mediated signaling of G protein-coupled receptors. Two new FR analogues (3 and 4) were isolated from A. crenata together with the known analogues 1 and 2. The structures of compounds 3 and 4 were established by NMR spectroscopic data and MS-based molecular networking followed by in-depth LCMS2 analysis. The latter approach led to the annotation of further FR analogues 5-9. Comparative bioactivity tests of compounds 1-4 along with the parent molecule FR showed high-affinity binding to Gq proteins in the low nanomolar range (IC50 = 2.3-16.8 nM) for all analogues as well as equipotent inhibition of Gq signaling, which gives important SAR insights into this valuable natural product. Additionally, FR was detected from leaves of five other Ardisia species, among them the non-nodulated leaves of Ardisia lucida, implying a much broader distribution of FR than originally anticipated.

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