Stefkó Dóra, Kúsz Norbert, Szemerédi Nikoletta, Barta Anita, Spengler Gabriella, Berkecz Róbert, Hohmann Judit, Vasas Andrea
Department of Pharmacognosy, Interdisciplinary Excellence Centre, University of Szeged, 6720 Szeged, Hungary.
Department of Medical Microbiology, Albert Szent-Györgyi Health Center, Albert Szent-Györgyi Medical School, University of Szeged, 6725 Szeged, Hungary.
Pharmaceutics. 2022 Mar 10;14(3):608. doi: 10.3390/pharmaceutics14030608.
Phenanthrenes are the main special metabolites of Juncaceae species from phytochemical, pharmacological, and chemotaxonomical points of view. The present study focused on the isolation, structure determination, and pharmacological investigation of phenanthrenes from Juncus ensifolius. Nineteen compounds, including 17 phenanthrenes, were identified from the methanol extract of the plant. Thirteen compounds, namely, ensifolins A−M (1−13), were obtained for the first time from natural sources. Four phenanthrenes [2-hydroxy-1,7-dimethyl-5-vinyl-9,10-dihydrophenanthrene (14), juncuenin B (15), juncatrin B (16), and sylvaticin A (17)], 4-hydroxybenzaldehyde (18) and luteolin (19) were isolated for the first time from J. ensifolius. Ensifolins A (1) and B (2) are structurally unique phenanthrenes, considering that they are flavonoid- (1) or benzaldehyde-adducts (2). The antiproliferative activity of all isolated compounds against HeLa, COLO 205, and COLO 320 cancer cells and a non-tumor (MRC-5) cell line was tested using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) viability assay. The luteolin-substituted phenanthrene ensifolin A (1) proved to be the most active against all three cancer cell lines (IC50 values 3.9−12.7 μM) and showed good selectivity (SI = 4.95) in the case of COLO 205. The best selectivity was recorded for ensifolins D (4, SI > 5.15, HeLa), H (8, SI > 8.13, HeLa), and 17 (SI > 9.43, HeLa). The synergistic activity of the compounds with doxorubicin was also tested on HeLa cells, and ensifolins E (5) and H (8) exhibited very strong synergism (CI < 0.1). In conclusion, these phenanthrenes are worthy of further investigation.
从植物化学、药理学和化学分类学的角度来看，菲类化合物是灯心草科植物的主要特殊代谢产物。本研究聚焦于从剑叶灯心草中分离菲类化合物、确定其结构并进行药理学研究。从该植物的甲醇提取物中鉴定出19种化合物，其中包括17种菲类化合物。13种化合物，即剑叶灯心草素A - M（1 - 13），首次从天然来源获得。4种菲类化合物[2 - 羟基 - 1,7 - 二甲基 - 5 - 乙烯基 - 9,10 - 二氢菲（14）、灯心草宁B（15）、灯心草卡特灵B（16）和森林灯心草素A（17）]、4 - 羟基苯甲醛（18）和木犀草素（19）首次从剑叶灯心草中分离得到。剑叶灯心草素A（1）和B（2）是结构独特的菲类化合物，因为它们分别是黄酮类加合物（1）或苯甲醛加合物（2）。使用3 -（4,5 - 二甲基噻唑 - 2 - 基）- 2,5 - 二苯基 - 2H - 四氮唑溴盐（MTT）活力测定法测试了所有分离化合物对HeLa、COLO 205和COLO 320癌细胞以及非肿瘤（MRC - 5）细胞系的抗增殖活性。木犀草素取代的菲类化合物剑叶灯心草素A（1）对所有三种癌细胞系表现出最强活性（IC50值为3.9 - 12.7 μM），并且在COLO 205细胞系中显示出良好的选择性（SI = 4.95）。剑叶灯心草素D（4，SI > 5.15，HeLa）、H（8，SI > 8.13，HeLa）和17（SI > 9.43，HeLa）记录到最佳选择性。还在HeLa细胞上测试了这些化合物与阿霉素的协同活性，剑叶灯心草素E（5）和H（8）表现出非常强的协同作用（CI < 0.1）。总之，这些菲类化合物值得进一步研究。
