Felegyi Kristóf, Garádi Zsófia, Rácz Bálint, Tóth Gábor, Papp Viktor, Boldizsár Imre, Dancsó András, Spengler Gabriella, Béni Szabolcs, Ványolós Attila
Department of Pharmacognosy, Semmelweis University, 1085 Budapest, Hungary.
Directorate of Drug Substance Development, Egis Pharmaceuticals Plc., 1475 Budapest, Hungary.
J Fungi (Basel). 2023 Sep 13;9(9):923. doi: 10.3390/jof9090923.
Polyporenic acids N-R (-), five novel 24-methylene lanostane triterpenes along with seven known polyporenic acids (-), were identified from the fruiting bodies of . The isolation of compounds - was performed by a combination of multistep flash chromatography and reversed-phase high-performance liquid chromatography (HPLC). The structure determination was carried out by extensive spectroscopic analysis, including 1D and 2D nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) experiments. The isolated fungal metabolites were investigated for their antiproliferative activity in vitro by 3-(4,5-dimethylthiazol2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay on the resistant Colo 320 human colon adenocarcinoma cell line expressing P-glycoprotein (ABCB1). The lanostane triterpenes exerted moderate antiproliferative activity with IC values in the range of 20.7-106.2 μM. A P-glycoprotein efflux pump modulatory test on resistant Colo 320 cells highlighted that fungal metabolites , , , and - have the ability to inhibit the efflux pump activity of cancer cells. Moreover, the drug interactions of triterpenes with doxorubicin were studied by the checkerboard method. Compounds -, and - interacted in a synergistic manner, while an outstanding potency was detected for compound , which was defined as strong synergism (CI = 0.276). The current study reveals that is a remarkable source of fungal steroids with considerable chemosensitizing activity on cancer cells.
从……的子实体中鉴定出了多孔酸N - R（-），五种新型的24 - 亚甲基羊毛甾烷三萜以及七种已知的多孔酸（-）。化合物……的分离通过多步快速柱色谱和反相高效液相色谱（HPLC）相结合的方法进行。结构测定通过广泛的光谱分析进行，包括一维和二维核磁共振（NMR）以及高分辨率电喷雾电离质谱（HR - ESI - MS）实验。通过在表达P - 糖蛋白（ABCB1）的耐药性Colo 320人结肠腺癌细胞系上进行3 -（4,5 - 二甲基噻唑 - 2 - 基）- 2,5 - 二苯基四氮唑溴盐（MTT）试验，对分离出的真菌代谢产物进行体外抗增殖活性研究。羊毛甾烷三萜表现出中等的抗增殖活性，IC值在20.7 - 106.2 μM范围内。对耐药性Colo 320细胞进行的P - 糖蛋白外排泵调节试验表明，真菌代谢产物……具有抑制癌细胞外排泵活性的能力。此外，通过棋盘法研究了三萜与阿霉素的药物相互作用。化合物……以协同方式相互作用，而化合物……检测到具有显著的效力，被定义为强协同作用（CI = 0.276）。当前研究表明，……是真菌甾体的一个重要来源，对癌细胞具有相当大的化学增敏活性。
