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
Abstract:
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[5.4.0.11,4]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:
Service
PDF(KB) Free
Print
0
Authors
Faliang An
Xiaobing Wang
Minghua Yang
Jun Luo
Lingyi Kong

References:
1. Guo Z. The modification of natural products for medical use. Acta Pharm Sin B 2017;7:119-36.
2. Tan QG, Luo XD. Meliaceous limonoids:chemistry and biological activities. Chem Rev 2011;111:7437-522.
3. Han ML, Shen Y, Wang GC, Leng Y, Zhang H, Yue JM. 11β-HSD1 inhibitors from Walsura cochinchinensis. J Nat Prod 2013;76:1319-27.
4. Ji KL, Zhang P, Hu HB, Hua S, Liao SG, Xu YK. Limonoids from the leaves and twigs of Walsura yunnanensis. J Nat Prod 2014;77:1764-9.
5. Luo XD, Wu SH, Ma YB, Wu DG. Tetranortriterpenoids from Walsura yunnanensis. J Nat Prod 2000;63:947-51.
6. Wang GC, Yu JH, Shen Y, Leng Y, Zhang H, Yue JM. Limonoids and triterpenoids as 11β-HSD1 inhibitors from Walsura robusta. J Nat Prod 2016;79:899-906.
7. Han ML, Shen Y, Leng Y, Zhang H, Yue JM. New rearranged limonoids from Walsura cochinchinensis. RSC Adv 2014;4:19150-8.
8. Nugroho AE, Okuda M, Yamamoto Y, Hirasawa Y, Wong CP, Kaneda T, et al. Walsogynes B-G, limonoids from Walsura chrysogyne. Tetrahedron 2013;69:4139-45.
9. Rao MS, Suresh G, Yadav PA, Prasad KR, Rani PU, Rao CV, et al. Piscidinols H-L, apotirucallane triterpenes from the leaves of Walsura trifoliata and their insecticidal activity. Tetrahedron 2015;71:1431-7.
10. An FL, Sun DM, Li RJ, Zhou MM, Yang MH, Yin Y, et al. Walrobsins A and B, two anti-inflammatory limonoids from root barks of Walsura robusta. Org Lett 2017;19:4568-71.
11. Zhang Y, An FL, Huang SS, Yang L, Gu YC, Luo J, et al. Diverse tritepenoids from the fruits of Walsura robusta and their reversal of multidrug resistance phenotype in human breast cancer cells. Phytochemistry 2017;136:108-18.
12. Yin S, Wang XN, Fan CQ, Liao SG, Yue JM. The first limonoid peroxide in the meliaceae family:walsuronoid A from Walsura robusta. Org Lett 2007;9:2353-6.
13. Zhou ZW, Yin S, Zhang HY, Fu Y, Yang SP, Wang XN, et al. Walsucochins A and B with an unprecedented skeleton isolated from Walsura cochinchinensis. Org Lett 2006;10:465-8.
14. Grkovic T, Pouwer RH, Vial ML, Gambini L, Noël A, Hooper JN, et al. NMR fingerprints of the drug-like natural-product space identify iotrochotazine A:a chemical probe to study parkinson's disease. Angew Chem Int Ed 2014;53:6070-4.
15. Liu Y, Zhou JL, Liu P, Sun S, Li P. Chemical markers' fishing and knockout for holistic activity and interaction evaluation of the components in herbal medicines. J Chromatogr A 2010;1217:5239-45.
16. Song HP, Wu SQ, Qi LW, Long F, Jiang LF, Liu K, et al. A strategy for screening active lead compounds and functional compound combinations from herbal medicines based on pharmacophore filtering and knockout/knockin chromatography. J Chromatogr A 2016;1456:176-86.
17. Jiang L. Three tetranortriterpenoids from Walsura yunnanensis. Chem Nat Compd 2013;48:1013-6.
18. O'Boyle NM, Vandermeersch T, Flynn CJ, Maguire AR, Hutchison GR. Confab-systematic generation of diverse low-energy conformers. J Cheminform 2011;3:8.
19. Li RJ, Gao CY, Guo C, Zhou MM, Luo J, Kong LY. The antiinflammatory activities of two major withanolides from Physalis minima via acting on NF-κB, STAT3, and HO-1 in LPS-stimulated RAW264.7 cells. Inflammation 2017;40:401-13.
20. Guo MM, An FL, Yu HY, Wei X, Hong MH, Lu YH. Comparative effects of schisandrin A, B, and C on Propionibacterium acnesinduced, NLRP3 inflammasome activation-mediated IL-1β secretion and pyroptosis. Biomed Pharmacother 2017;96:129-36.
21. Guo MM, An FL, Wei X, Hong MH, Lu YH. Comparative effects of schisandrin A, B, and C on acne-related inflammation. Inflammation 2017;40:2163-72.
22. Dolomanov OV, Bourhis LJ, Gildea RJ, Howard JAK, Puschmann H. J Appl Cryst 2009;42:339-41.