Semisynthesis, an Anti-Inflammatory Effect of Derivatives of 1β-Hydroxy Alantolactone from Inula britannica

• Main Authors: Lin Chen, Jian-Ping Zhang, Xin Liu, Jiang-Jiang Tang, Ping Xiang, Xing-Ming Ma
• Format: Article
• Language: English
• Published: MDPI AG 2017-10-01
• Series: Molecules
• Subjects: 1β-hydroxy alantolactone; semisynthesis; anti-inflammatory activity
• Online Access: https://www.mdpi.com/1420-3049/22/11/1835
• ISSN: 1420-3049

1β-hydroxy alantolactone, a sesquiterpene lactone mainly isolated from Inula genus plants, exhibits potent anti-inflammatory and anticancer activities. In this work, 1β-hydroxy alantolactone was isolated and five derivatives were prepared through different reactions at the C1-OH and C13-methylene motifs. The structure–activity relationships (SAR) of anti-inflammatory effects against NO production in RAW264.7 cells showed that the α-methylene-γ-butyrolactone motif was essential for NO production suppression and that retaining the C1-OH group can remarkably improve this effect. The NF-κB signaling pathway plays a pivotal role in the regulation of NO expression. Moreover, the levels of p65 and p50 phosphorylation were investigated and active compound 1 inhibited phosphorylation of p65 and p50 in TNF-α-induced NF-κB signaling. Further molecular docking suggested that 1 may target the p65 of NF-κB.