Ramirez-Garcia Jennie L, Grant Elysha-Rose K, Salamat Antonio, Anker Mathew D, Cameron Scott A, Kelly Michelle, Matoto S Vailala, Barber Jacqueline M, Northcote Peter T, Williams-Spence Jenni W, La Flamme Anne C, Harvey Joanne E, Singh A Jonathan, Keyzers Robert A
School of Chemical and Physical Sciences, Victoria University of Wellington, P.O. Box 600, 6140 Wellington, New Zealand.
Centre for Biodiscovery, Victoria University of Wellington, P.O. Box 600, 6140 Wellington, New Zealand.
J Nat Prod. 2025 Jan 24;88(1):162-174. doi: 10.1021/acs.jnatprod.4c01218. Epub 2024 Dec 23.
Spectroscopy-guided isolation of extracts of the Tongan marine sponge cf. (Lamarck, 1814) has resulted in the reisolation of the labdane diterpenoid luakuliide A () and one new congener, luakulialactam A (). In addition to establishing the absolute configuration of , synthetic modifications to the luakuliide framework at key positions has created a set of six derivatives (-) which were used to interrogate a structure-activity relationship relating to the immunomodulatory effects of luakuliide A. This revealed that compounds , , and , 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.
对汤加海洋海绵cf. （拉马克，1814年）提取物进行光谱引导分离，重新分离出了半日花烷二萜鲁库利德A（）和一个新的同系物鲁库利阿内酰胺A（）。除了确定的绝对构型外，在关键位置对鲁库利德骨架进行的合成修饰产生了一组六个衍生物（-），用于研究与鲁库利德A免疫调节作用相关的构效关系。结果表明，带有取代呋喃基序的化合物、和在原代巨噬细胞中表现出强大活性，通过抑制促炎细胞因子的产生，同时在纳摩尔浓度下上调细胞代谢和抗炎性白细胞介素-10的产生。这是一种与向与伤口愈合和炎症消退相关的抗炎表型调节的巨噬细胞一致的活性谱。
