Damu Amooru G, Kuo Ping-Chung, Su Chung-Ren, Kuo Tsung-Hsiao, Chen Tzu-Hsuan, Bastow Kenneth F, Lee Kuo-Hsiung, Wu Tian-Shung
Department of Chemistry, National Cheng Kung University, Tainan 701, Taiwan, Republic of China.
J Nat Prod. 2007 Jul;70(7):1146-52. doi: 10.1021/np0701374. Epub 2007 Jun 20.
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 microg/mL. Structure-activity relationship analysis indicated that withanolides and physalins with 4beta-hydroxy-2-en-1-one and 5beta,6beta-epoxy moieties are potential cytotoxic agents.
在初步生物筛选之后，开始了对酸浆的植物化学研究。采用体外细胞毒性活性测定法，以培养的HONE-1和NUGC细胞为指标，对全株甲醇提取物的氯仿可溶物和正丁醇可溶物进行分馏，从而分离出7种新的维A醇类化合物，即酸浆角素B-H（1-7），以及一种新的微量酸浆苦素，酸浆苦素W（8），同时还得到了14种已知化合物，包括酸浆普伦A、酸浆醇内酯、二氢维A醇内酯E、酸浆醇内酯A、酸浆苦素A，以及酸浆苦素B、D、F、G、I、J、T、U和V。通过光谱方法（一维和二维核磁共振及质谱）以及基于核Overhauser效应光谱（NOESY）相关和耦合常数分析的相对立体化学归属，对新化合物（1-8）进行了全面表征。对这些化合物针对一组人类癌细胞系的生物学评价显示出广泛的细胞毒性活性。酸浆角素B（1）、酸浆苦素D（10）和F（11）对一组人类癌细胞系表现出强效细胞毒性活性，半数有效浓度（EC50）值范围为0.2至1.6微克/毫升。构效关系分析表明，具有4β-羟基-2-烯-1-酮和5β,6β-环氧部分的维A醇类化合物和酸浆苦素是潜在的细胞毒性剂。
