Isolation, structures, and structure-cytotoxic activity relationships of withanolides and physalins from Physalis angulata
Isolation, structures, and structure-cytotoxic activity relationships of withanolides and physalins from Physalis angulata
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DOI：
10.1021/np0701374
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发表时间：
2007-07-01
影响因子：
5.1
通讯作者：
Wu, Tian-Shung
中科院分区：
文献类型：
--
作者：
Damu, Amooru G.;Kuo, Ping-Chung;Wu, Tian-Shung
在对酸浆进行初步生物学筛选的基础上，开展了酸浆植物化学成分的研究。通过使用培养的HONE-1和NUGC细胞的体外细胞毒性活性测定来指导来自全植物的MeOH提取物的CHCl 3和n-BuOH可溶物的分级，并导致分离出七种新的睡茄内酯，睡茄素B-H（1-7），和一种新的次要酸浆素，酸浆素W（8），沿着14种已知化合物，包括physaprun A，睡茄素，二氢睡茄素E，physanestrine A，新化合物（1-8）通过光谱方法（1D和2D NMR和MS）和基于NOESY相关性和偶合常数分析的相对立体化学归属的组合来充分表征。这些化合物对一组人癌细胞系的生物学评价显示出广泛的细胞毒活性。Withangulatin B（1）和酸浆素D（10）和F（11）对一组人类癌细胞系显示出强效细胞毒活性，EC 50值范围为0.2 - 1.6 μ g/mL。构效关系分析表明，具有4 β-羟基-2-烯-1-酮和5 β，6 β-环氧基的睡茄内酯和酸浆素是潜在的细胞毒性剂。
Phytochemical investigation of Physalis angulata was initiated following primary biological screening. Fractionation of CHCl3 and n-BuOH solubles of the MeOH extract from the whole plant was guided by in vitro cytotoxic activity assay using cultured HONE-1 and NUGC cells and led to the isolation of seven new withanolides, withangulatins B-H (1-7), and a new minor physalin, physalin W (8), along with 14 known compounds, including physaprun A, withaphysanolide, dihydrowithanolide E, physanolide A, withaphysalin A, and physalins B, D, F, G, I, J, T, U, and V. New compounds (1-8) were fully characterized by a combination of spectroscopic methods (1D and 2D NMR and MS) and the relative stereochemical assignments based on NOESY correlations and analysis of coupling constants. Biological evaluation of these compounds against a panel of human cancer cell lines showed broad cytotoxic activity. Withangulatin B (1) and physalins D (10) and F (11) displayed potent cytotoxic activity against a panel of human cancer cell lines with EC50 values ranging from 0.2 to 1.6 mu g/mL. Structure-activity relationship analysis indicated that withanolides and physalins with 4 beta-hydroxy-2-en-1-one and 5 beta,6 beta-epoxy moieties are potential cytotoxic agents.