1. Academic Validation
  2. Structurally diversified ent-kaurane and abietane diterpenoids from the stems of Tripterygium wilfordii and their anti-inflammatory activity

Structurally diversified ent-kaurane and abietane diterpenoids from the stems of Tripterygium wilfordii and their anti-inflammatory activity

  • Bioorg Chem. 2021 Oct;115:105178. doi: 10.1016/j.bioorg.2021.105178.
Xiao-Qiong Zhou 1 Si-Qi Li 1 Cai-Ceng Liao 1 Wei-Feng Dai 1 Kai-Rui Rao 1 Xiu-Rong Ma 1 Rong-Tao Li 2 Xuan-Qin Chen 3
Affiliations

Affiliations

  • 1 Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, Yunnan, P.R. China.
  • 2 Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, Yunnan, P.R. China. Electronic address: rongtaolikm@163.com.
  • 3 Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, Yunnan, P.R. China. Electronic address: chenxuanqin12@sina.com.
Abstract

Four undescribed ent-kaurane Diterpenoids, wilkaunoids A - D (1-4), and three undescribed abietane Diterpenoids, wilabinoids A - C (13-15), along with thirteen known ones (5-12 and 16-20), were isolated from Tripterygium wilfordii. Their structures were elucidated by extensive spectroscopic methods, electroniccirculardichroism calculation, and X-ray diffraction analysis. Compounds 1 and 2 were a pair of C-19 epimers of ent-kaurane Diterpenoids, featuring a rare 19,20-epoxy-19,20-dimethoxy-kaurane fragment. Compound 3 possessed a rare naturally occurring 1,3-dioxacyclohexane moiety. Compounds 13 and 15 represented the first example of abietane Diterpenoids with an isovalerate substitution from the genus of Tripterygium. The possible biosynthetic pathways of 1-3 were postulated. The effect of 1-20 on nitric oxide production was examined in lipopolysaccharide-stimulated RAW 264.7 cells. Abietane diterpenoid Quinones 7-13 (IC50: 1.9-10.2 μM) exhibited the significant activity to inhibit nitric oxide production versus positive control (NG-monomethyl-l-arginine acetate salt, IC50 = 24.9 μM). The structure activity relationship of 7-13 in inhibiting nitric oxide production was then discussed. The most potent 7 and 8 were found to significantly suppress the expression of cyclooxygenase-2 and inducible nitric oxide synthase proteins, showing a good anti-inflammatory potential. The findings provided some valuable insights for the discovery and structural modification of abietane Diterpenoids towards anti-inflammatory lead compounds.

Keywords

Abietane diterpenoids; Anti-inflammatory activity; Ent-kaurane diterpenoids; Tripterygium wilfordii; Wilabinoids A−C; Wilkaunoids A−D.

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