Original articles
Faliang An, Xiaobing Wang, Minghua Yang, Jun Luo, Lingyi Kong. Bioactive A-ring rearranged limonoids from the root barks of Walsura robusta[J]. Acta Pharmaceutica Sinica B, 2019, 9(3): 545-556

Bioactive A-ring rearranged limonoids from the root barks of Walsura robusta
Faliang An, Xiaobing Wang, Minghua Yang, Jun Luo, Lingyi Kong
Jiangsu Key Laboratory of Bioactive Natural Product Research and State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China
Screening active natural products, rapid identification, and accurate isolation are of great important for modern natural lead compounds discovery1. We hereby reported the isolation of seven new neotecleanin-type limonoids (1-7), seven new limonoids with 5-oxatricyclo[,4]hendecane ring system (8-14), and two new precursors (15-16) together with four known limonoids (17-20) from the root barks of Walsura robusta. Their structures, including their absolute configurations, were elucidated based on analyses of HR-ESI-MS, 1D/2D NMR, ECD spectrum calculations and singlecrystal X-ray diffraction techniques. Compounds 2, 8, 9, 11, 13, 14, 18 showed significant anti-inflammatory activities in LPS-induced RAW 264.7 cell line, BV2 microglial cells, and Propionibacterium acnes-stimulated THP-1 human monocytic cells. Walrobsin M (11) exhibited anti-inflammatory activity with IC50 value of 7.96±0.36 μmol/L, and down-regulated phosphorylation levels of ERK and p38 in a dose-dependent manner.
Key words:    Walsura robusta    limonoid    Neotecleanin-type    ECD spectrum calculation    Single-crystal X-ray diffraction    Anti-inflammatory activity    Propionibacterium acnes    THP-1 human monocytic cell   
Received: 2018-11-22     Revised:
DOI: 10.1016/j.apsb.2019.02.009
Funds: Financial support for this study by the National Natural Science Foundation of China (31470416, China), the Outstanding Youth Fund of the Basic Research Program of Jiangsu Province (BK20160077, China), the Program for Changjiang Scholars and Innovative Research Team in University (IRT_15R63, China), and the "Double First-Class" University project (CPU2018GY08, China).
Corresponding author: Lingyi Kong, Jun Luo     Email:cpu_lykong@126.com;luojun@cpu.edu.cn
Author description:
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Faliang An
Xiaobing Wang
Minghua Yang
Jun Luo
Lingyi Kong

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