Computationally-Assisted Discovery and Assignment of a New Class of 6/6/5/5 Fused-Ring Diterpene Acting as Pregnane X Receptor Ligands from Isodon serra.

IF 3.3 2区生物学 Q2 CHEMISTRY, MEDICINAL Journal of Natural Products Pub Date : 2024-10-25 Epub Date: 2024-09-24 DOI:10.1021/acs.jnatprod.4c00759

Zhiwei Bian, Xiaoying Liu, Shian Hu, Hongyi Li, Jared S Wood, R Thomas Williamson, Jiabao Liu, Ying Chen, Jin Shi, Carolyn L Cummins, Daneel Ferreira, Yeun-Mun Choo, Shengpeng Wang, Mark T Hamann, Xiaojuan Wang

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Abstract

We report here the orchestration of molecular ion networking (MoIN) and a set of computationally assisted structural elucidation approaches in the discovery and assignment of a new class of rearranged 4,5-seco-abietane diterpenoids including serra A (1), which possesses an unusual 6/6/5/5 fused-ring skeleton system, together with two previously unreported diterpenoids serras B-C (2-3) and five known compounds were isolated from Isodon serra (I. serra). The structures were elucidated by spectroscopic analysis in conjunction with computationally assisted structure elucidation tools. In silico, serras A-C (1-3) bind well to PXR, suggesting their potential role in reducing inflammation. The results of serra A (1) with hPXR demonstrated agonist activity with an EC₅₀ value of 15 μM. Serra A (1), graciliflorin F (4), gerardianin C (5), 11,12,15-trihydroxy-8,11,13-abietatrien-7-one (6), rabdosin D (7), and 15-hydroxysalprionin (8) exhibited promising anti-inflammatory activities in lipopolysaccharide (LPS)-induced RAW 267.4 cells, and their inhibition rates on NO production were more than 65% at 10 μM.

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通过计算辅助从 Isodon serra 中发现并鉴定一类可作为孕烷 X 受体配体的新型 6/6/5/5 Fused-Ring Diterpene。

我们在此报告了分子离子网络（MoIN）和一套计算辅助结构阐释方法在发现和分配一类新的重新排列的 4,5-seco-abietane二萜类化合物中的协调作用，其中包括 Serra A (1)，它拥有一个不寻常的 6/6/5/5 熔环骨架系统，以及两个以前未报道过的二萜类化合物 serras B-C (2-3)，还有从 Isodon serra (I. serra) 中分离出的五个已知化合物。这些化合物的结构是通过光谱分析结合计算辅助结构阐明工具阐明的。在硅学中，丝氨酸 A-C （1-3）与 PXR 结合良好，表明它们在减少炎症方面具有潜在作用。血清 A（1）与 hPXR 的结合结果显示了激动剂活性，EC50 值为 15 μM。在脂多糖（LPS）诱导的 RAW 267.4 细胞中，Serra A (1)、蟛蜞菊素 F (4)、刺五加素 C (5)、11,12,15-三羟基-8,11,13-阿片三烯-7-酮 (6)、鸦胆子素 D (7) 和 15-hydroxysalprionin (8) 表现出良好的抗炎活性，在 10 μM 时对 NO 生成的抑制率超过 65%。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Natural Products 生物-药学

CiteScore

9.10

自引率

5.90%

发文量

294

审稿时长

2.3 months

期刊介绍： The Journal of Natural Products invites and publishes papers that make substantial and scholarly contributions to the area of natural products research. Contributions may relate to the chemistry and/or biochemistry of naturally occurring compounds or the biology of living systems from which they are obtained. Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin. When new compounds are reported, manuscripts describing their biological activity are much preferred. Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin.