Matias Diogo, Nicolai Marisa, Saraiva Lucília, Pinheiro Rute, Faustino Célia, Diaz Lanza Ana, Pinto Reis Catarina, Stankovic Tijana, Dinic Jelena, Pesic Milica, Rijo Patrícia
Research Center for Biosciences & Health Technologies (CBIOS), Universidade Lusófona de Humanidades e Tecnologias, Campo Grande 376, 1749-024 Lisboa, Portugal.
Department of Biomedical Sciences, Faculty of Pharmacy, University of Alcalá, Campus Universitario, 28871 Alcalá de Henares, Spain.
ACS Omega. 2019 May 2;4(5):8094-8103. doi: 10.1021/acsomega.9b00512. eCollection 2019 May 31.
Cytotoxicity screenings have identified plants as potential sources of antitumor lead compounds. In this work, several extracts from were prepared using different solvents (acetone, methanol, and supercritical CO) and extraction techniques (maceration, ultrasound-assisted, and supercritical fluid extraction), and their chemical composition was detailed using high-performance liquid chromatography with a diode array detector. The cytotoxic activity of the major compounds identified, namely, rosmarinic acid () and abietane diterpenes 7α,6β-dihydroxyroyleanone (), 7α-formyloxy-6β-hydroxyroyleanone (), 7α-acetoxy-6β-hydroxyroyleanone (), and coleon U (), was evaluated in a battery of human cancer cell lines, including breast (MDA-MB-231, MCF-7), colon (HCT116), and lung (NCI-H460, NCI-H460/R) cancer, and also in healthy lung (MCR-5) cells. Royleanone () was isolated for the first time from , and its full spectroscopic characterization (proton and carbon nuclear magnetic resonance) was accomplished. A high selectivity for lung cancer cells was observed for royleanones (, ) with selectivity indexes of 4.3 and 3.2, respectively. The observed results combined with literature data allowed the establishment of important structure-activity relationships for substituted royleanone abietanes, such as the requirement for an electron-donating group at positions 6 and/or 7 in the abietane skeleton, and an improved cytotoxic effect for substituents with log values between 2 and 5.
细胞毒性筛选已确定植物是抗肿瘤先导化合物的潜在来源。在这项工作中，使用不同溶剂（丙酮、甲醇和超临界二氧化碳）和提取技术（浸渍法、超声辅助提取法和超临界流体萃取法）制备了几种来自[植物名称未给出]的提取物，并使用配备二极管阵列检测器的高效液相色谱详细分析了它们的化学成分。对所鉴定的主要化合物，即迷迭香酸（[具体成分未给出]）和枞烷二萜类化合物7α,6β - 二羟基瑞香烷酮（[具体成分未给出]）、7α - 甲酰氧基 - 6β - 羟基瑞香烷酮（[具体成分未给出]）、7α - 乙酰氧基 - 6β - 羟基瑞香烷酮（[具体成分未给出]）和科列昂U（[具体成分未给出]），在一系列人类癌细胞系中进行了细胞毒性活性评估，这些细胞系包括乳腺癌（MDA - MB - 231、MCF - 7）、结肠癌（HCT116）和肺癌（NCI - H460、NCI - H460/R），同时也在健康肺细胞（MCR - 5）中进行了评估。首次从[植物名称未给出]中分离出瑞香烷酮（[具体成分未给出]），并完成了其完整的光谱表征（质子和碳核磁共振）。观察到瑞香烷酮类化合物（[具体成分未给出]）对肺癌细胞具有高选择性，其选择性指数分别为4.3和3.2。观察结果与文献数据相结合，建立了取代瑞香烷酮枞烷类化合物重要的构效关系，例如在枞烷骨架的6位和/或7位需要一个供电子基团，以及对数P值在2至5之间的取代基具有更好的细胞毒性作用。
