Department of Applied Biology, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan.
Bioorg Med Chem Lett. 2012 Jan 1;22(1):207-11. doi: 10.1016/j.bmcl.2011.11.029. Epub 2011 Nov 16.
Inflammatory cytokines, such as interleukin-1α (IL-1α) and tumor necrosis factor-α (TNF-α), induce the intracellular signaling pathway leading to the activation of nuclear factor κB (NF-κB). A series of eudesmane-type sesquiterpene lactones possessing an α-methylene γ-lactone group and/or an α-bromo ketone group were synthesized and evaluated for their inhibitory effects on the NF-κB-dependent gene expression and signaling pathway. Our present study reveals that eudesmane-type α-methylene γ-lactones and α-bromo ketones inhibit multiple steps in the NF-κB signaling pathway induced by IL-1α and TNF-α.
炎症细胞因子，如白细胞介素-1α（IL-1α）和肿瘤坏死因子-α（TNF-α），诱导导致核因子 κB（NF-κB）激活的细胞内信号通路。一系列具有α-亚甲基γ-内酯基团和/或α-溴酮基团的艾里莫芬烷型倍半萜内酯被合成并评估其对 NF-κB 依赖性基因表达和信号通路的抑制作用。本研究揭示艾里莫芬烷型α-亚甲基γ-内酯和α-溴酮抑制由 IL-1α 和 TNF-α 诱导的 NF-κB 信号通路中的多个步骤。
