Diterpenoids with a novel 6/5-5 spiro tricyclic skeleton from Orthosiphon wulfenioides and their NLRP3 inflammasome inhibitory activity

Authors：Tu, Wen-Chao; Zhang, Xing-Jie; Zhao, Ying-Xin; Chen, Wei-Chi; Zhang, Xing-Yu; Yang, Chang-Lin; Zeb, Muhammad Aurang; Li, Xiao-Li^*; Sakah, Kaunda-Joseph; Zhang, Rui-Han; Liu, Mei-Feng^*; Xiao, Wei-Lie^*

Source：Organic Chemistry Frontiers, 2023, 10(12): 2898-2906.

DOI：10.1039/d3qo00247k

• REARRANGED TRITERPENOIDS
• NATURAL-PRODUCT
• STRATEGIES
• ACTIVATION

Wulfenioidins A-C (1-3) with an unprecedented 6/5-5 tricyclic skeleton featuring the unusual spiro[4.4] nonane were isolated from the whole plant of Orthosiphon wulfenioides. Their structures were elucidated by X-ray diffraction, quantum chemical calculations, and extensive spectroscopic methods. Putative biosynthetic pathways of 1-3 were proposed. Compound 3 showed a potent inhibitory effect against the NLRP3 inflammasome with an IC50 value of 1.05 mu M and significantly blocked the NLRP3 inflammasomeinduced pyroptosis by inhibiting caspase-1 activation, GSDMD-NT production, and IL-1 beta secretion in J774A.1 cells.

• Institution
  云南大学