目的 研究小酸浆Physalin minima中醉茄内酯（withanolides）类化学成分，并评价其对结肠癌细胞（HCT-116）、三阴性乳腺癌细胞（MDA-MB-231）和红白血病细胞（HEL）的体外抗肿瘤活性。方法 综合运用多种色谱技术进行分离纯化，结合红外、高分辨质谱、核磁共振及电子圆二色谱等波谱方法进行结构鉴定，采用MTT法测定所得化合物对上述3种肿瘤细胞的增殖抑制活性。结果 从小酸浆地上部分中分离鉴定8个withanolides类化合物，分别鉴定为 (8R,9S,10R,13R, 14R,16S,17R,20S,22R,24S)-14α,17α:16α,24α-二环氧-13α,14β,22α-三羟基-1,15-二酮-13,14-开环麦角甾-2,5-二烯-18,20-内酯（1）、(8R,9S,10R,13R,14R,16S,17R,20S,22R,24R,25R)-14α,17α:14,27-二环氧-13α,22α-二羟基-1,15-二酮-13,14-开环麦角甾-2,5-二烯-18,20-内酯-24-丙酸（2）、5α-乙氧基-6β-羟基-5,6-二氢酸浆素B（3）、physalin VI（4）、physaminin F（5）、physagulide D（6）、pubesenolide（7）、physaminilide I（8）。体外抗肿瘤活性表明，化合物1、3和5对HCT-116细胞具有良好的抑制活性，半数抑制浓度（median inhibition concentration，IC₅₀）值为（10.97±1.62）～（39.20±2.17）μmol/L；化合物3对MDA-MB-231细胞的IC₅₀值为（19.36±1.03）μmol/L；化合物1、3和4对HEL细胞的IC₅₀值为（8.27±0.37）～（38.97±1.77）μmol/L。结论 化合物1和2为新化合物，化合物1是首个22,26-开环/降碳酸浆苦素，命名为酸浆内酯A；而化合物2是首个具有24-丙酸结构以及C-14与C-27之间形成醚桥的22,26-开环酸浆苦素，命名为酸浆内酯B。化合物1、3～5对3种不同肿瘤细胞系表现出不同程度的抑制作用，表明该类化合物具备开发成为抗肿瘤药物的潜力，值得深入研究。

Objective To investigate the withanolides from the aerial parts of Physalis minima and evaluate their in vitro anti-tumor activities against human colon cancer (HCT-116), triple-negative breast cancer (MDA-MB-231), and human erythroleukemia (HEL) cell lines. Methods The chemical constituents were isolated and purified using various chromatographic techniques. Their structures were elucidated through a comprehensive analysis of spectroscopic data, including infrared (IR), high-resolution mass spectrometry (HRMS), nuclear magnetic resonance (NMR), and electronic circular dichroism (ECD). The proliferation inhibitory activitiesof the isolated compounds against the above three cancer cell lines were evaluated using the MTT assay. Results Eight withanolides were isolated and identified from the aerial parts of P. minima, including two new compounds (1 and 2), which were characterized as (8R,9S,10R,13R,14R,16S,17R,20S,22R,24S)-14α,17α:16α,24α-diepoxy-13α,14β,22α-trihydroxy-1,15-dione-13,14-seco-ergosta-2,5-diene- 18,20-olide (1) and (8R,9S,10R,13R,14R,16S,17R,20S,22R,24R,25R)-14α,17α:14,27-diepoxy-13α,22α-dihydroxy-1,15-dione-13,14-seco-ergosta-2,5-diene-18,20-olide-24-propionic acid (2). The known compounds were identified as 5α-ethoxy-6β-hydroxy-5,6-dihydrophysalin B (3), physalin VI (4), physaminin F (5), physagulide D (6), pubesenolide (7), and physaminilide I (8). The in vitro bioassay results demonstrated that three compounds (1, 3, and 5) exhibited potent inhibitory activities against HCT-116 cells, with IC₅₀ values ranging from (10.97 ±1.62) to (39.20 ±2.17) μmol/L. Compound 3 displayed an IC₅₀ value of (19.36 ±1.03) μmol/L against MDA-MB-231 cells. Additionally, three compounds (1, 3, and 4) showed inhibitory effects on HEL cells, with IC₅₀ values ranging from (8.27 ±0.37) to (38.97 ±1.77) μmol/L. Conclusion Compounds 1 and 2 are new compounds. Compound 1 represents the first reported 22, 26-seco-nor-physalin, named phyminate A , while compound 2 is the first 22,26-seco-physalin featuring a 24-propionic acid moiety and a C-14/C-27 ether bridge, named phyminate B. The inhibitory activities of compounds 1, 3—5 against three tumor cell lines indicate their potential as anti-cancer candidates, justifying in-depth study.

R284.1

国家自然科学基金资助项目（32270413）；国家自然科学基金资助项目（82360826）；国家自然科学基金资助项目（82560693）