Natural and Semisynthetic Immunomodulatory Luakuliide Labdane Diterpenoids.

IF 3.3 2区生物学 Q2 CHEMISTRY, MEDICINAL

Journal of Natural Products Pub Date : 2025-01-24 Epub Date: 2024-12-23 DOI:10.1021/acs.jnatprod.4c01218

Jennie L Ramirez-Garcia, Elysha-Rose K Grant, Antonio Salamat, Mathew D Anker, Scott A Cameron, Michelle Kelly, S Vailala Matoto, Jacqueline M Barber, Peter T Northcote, Jenni W Williams-Spence, Anne C La Flamme, Joanne E Harvey, A Jonathan Singh, Robert A Keyzers

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引用次数: 0

Abstract

Spectroscopy-guided isolation of extracts of the Tongan marine sponge Hyattella cf. intestinalis (Lamarck, 1814) has resulted in the reisolation of the labdane diterpenoid luakuliide A (1) and one new congener, luakulialactam A (2). In addition to establishing the absolute configuration of 1, synthetic modifications to the luakuliide framework at key positions has created a set of six derivatives (3-8) which were used to interrogate a structure-activity relationship relating to the immunomodulatory effects of luakuliide A. This revealed that compounds 4, 5, and 6, bearing substituted furan motifs, show potent activity in primary macrophages by inhibiting pro-inflammatory cytokine production, while upregulating cellular metabolism and anti-inflammatory IL-10 production at nanomolar concentrations. This is an activity profile consistent with macrophages modulated toward an anti-inflammatory phenotype associated with wound-healing and resolution of inflammation.

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天然和半合成免疫调节的陆库利特二萜。

光谱引导下对汤安海绵体Hyattella cf. ntestinalis （Lamarck, 1814）提取物进行了分离，重新分离出了labdane二萜类化合物luakuliide A(1)和一个新的同族化合物luakulialactam A(2)。对陆库利特框架关键位置的合成修饰产生了一组6个衍生物（3-8），用于探究陆库利特a免疫调节作用的结构-活性关系。这表明，含有取代呋喃基序的化合物4、5和6通过抑制促炎细胞因子的产生，在原代巨噬细胞中显示出强大的活性。同时在纳摩尔浓度下上调细胞代谢和抗炎IL-10的产生。这是一种与巨噬细胞向与伤口愈合和炎症消退相关的抗炎表型调节一致的活性谱。

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.