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Anti-Inflammatory Lindenane Sesquiterpenoid Dimers from the Roots of Sarcandra glabra
Yunpeng Sun1, Yaqi Li1, Letian Cui1
1Jiangsu Key Laboratory of Bioactive Natural Product Research, State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, People's Republic of China.
Abstract:
Sarglaroids A-H (1-8), eight new lindenane dimers, and a monomer sarglaroid I (9), along with fourteen known analogues (10-23), were isolated from the roots of Sarcandra glabra. The planar structures and the absolute configurations were elucidated by HR-MS, NMR, ECD calculations, and X-ray diffraction crystallography. Sarglaroid A (1) was identified as a rare 8,9-seco lindenane dimer with a unique 5/5/5 tricyclic system. The biological evaluation showed that compounds 1 and 13 potently inhibited NO production with IC50 values at 19.8 ± 1.06 and 10.7 ± 0.25 μM, respectively, and had no cytotoxicity to RAW264.7 cells. Compound 6 significantly inhibited the LPS-/ATP-induced IL-1β release by inactivating the NLRP3 inflammasome through inhibiting the initiation and assembly by affecting the K+ efflux. Compounds 2 and 3 inhibited the proliferation of MCF-7 and MDA-MB-231 with IC50 values ranging from 5.4 to 10.2 μM.

