Natural and Semisynthetic Immunomodulatory Luakuliide Labdane Diterpenoids.

IF 3.3 2区生物学 Q2 CHEMISTRY, MEDICINAL Journal of Natural Products Pub 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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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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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.