Brujavanoids A–U, structurally diverse apotirucallane-type triterpenoids from Brucea javanica and their anti-inflammatory effects

• Published in: Bioorganic chemistry 2022-10, Vol.127, p.106012-106012, Article 106012
• Main Authors: Hu, Zhuo-Fan, Su, Jun-Cheng, Sun, Xing, Xia, Ru-Feng, Wu, Jia-Le, Fu, Xiao-Na, Zhang, Bing-Zhu, Chen, Jia-Chun, Wan, Luo-Sheng
• Format: Article
• Language: English
• Subjects: Anti-inflammatory; Apotirucallane; Brucea javanica; Simaroubaceae; Triterpenoid
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2022.106012

Extensive phytochemical investigation on the methanol extract of the inflorescences, twigs, and leaves of Brucea javanica led to the isolation and identification of 27 triterpenoids, including21 previously undescribed ones, named brujavanoids A–U (1–21). Their structures were determined based on comprehensive spectroscopic analysis and single-crystal X-ray diffraction. Of these compounds, brujavanoid A (1) represents the first apotirucallane-type triterpenoid with a novel 19(10→9)abeo motif, and brujavanoids B and C (2–3) are the first apotirucallane-type triterpenoids with a rarely occurring 14-hydorxy-15,16-epoxy fragment. All the isolates were evaluated for their anti-inflammatory effect in an LPS-activated RAW264.7 cells model. Furthermore, the most active one, brujavanoid E (5), can suppress the transcriptional expression of typical proinflammatory mediators and inhibit the nuclear translocation of NF-κB p65 in the LPS- activated RAW264.7 cells. [Display omitted] •27 Apotirucallane-type triterpenoids including 21 undescribed ones were isolated from Brucea javanica.•The absolute configurations of compounds 1–2, 6, 18 and 11 were established by X-ray diffraction.•Compound 1 represents the first apotirucallane-type triterpenoid with a novel 19(10 → 9)abeo motif.•Compounds 2 and 3 are the first apotirucallane-type triterpenoids with a rarely occurring 14-hydorxy-15,16-epoxy fragment.•Compounds 5, 7, 16, and 20 displayed moderate to significant anti-inflammatory effect.•Compound 5 can suppress the transcriptional expression of typical pro-inflammatory mediators and inhibit the nuclear translocation of NF-κB p65. Extensive phytochemical investigation on the methanol extract of the inflorescences, twigs, and leaves of Brucea javanica led to the isolation and identification of 27 triterpenoids, including 21 previously undescribed ones, named brujavanoids A–U (1–21). Their structures were determined based on comprehensive spectroscopic analysis and single-crystal X-ray diffraction. Of these compounds, brujavanoid A (1) represents the first apotirucallane-type triterpenoid with a novel 19(10 → 9)abeo motif, and brujavanoids B and C (2–3) are the first apotirucallane-type triterpenoids with a rarely occurring 14-hydorxy-15,16-epoxy fragment. All the isolates were evaluated for their anti-inflammatory effect in an LPS-activated RAW264.7 cells model. Furthermore, the most active one, brujavanoid E (5), can suppress the transcriptional expression of typical pro-inf