Cytotoxic Clerodane Diterpenoids from the Leaves of <i>Casearia grewiifolia</i>

Two new clerodane diterpenoids (1 and 2) and the known compound caseanigrescen D (3) were isolated from the leaves of Casearia grewiifolia by bioassay-guided fractionation. Their structures were determined by analyses of MS and 2D NMR data. The absolute configurations of 1 and 3 were established by analysis of X-ray diffraction data. Compounds 1–3 were evaluated for their cytotoxicity against four cancer cell lines, KB (mouth epidermal carcinoma cells), HepG-2 (human liver hepatocellular carcinoma cells), LU-1 (human lung adenocarcinoma cells), and MCF-7 (human breast cancer cells). Caseagrewifolin B (2) had inhibitory activity against KB and HepG-2 cell lines with IC50 values of 6.2 to 7.0 μM, respectively. When tested against the normal cells (NIH/3T3), caseagrewifolin B (2) exhibited a significant selective inhibition against cancer cells in comparison with the normal cells. Caseanigrescen D (3) was cytotoxic against four cancer cell lines; however it had no selective inhibition compared with normal cells.本研究通过生物活性导向分离法，从大叶脚骨脆（Casearia grewiifolia）的叶片中分离得到2个新的克罗烷型二萜（clerodane diterpenoids，化合物1和2）以及1个已知化合物caseanigrescen D（化合物3）。通过质谱（MS）和二维核磁共振（2D NMR）数据分析，确定了所有化合物的平面结构。化合物1和3的绝对构型通过X射线衍射（X-ray diffraction）数据分析得以确立。对化合物1至3开展了针对4种癌细胞系的细胞毒性评价，所测试的癌细胞系包括KB细胞（人口腔表皮癌细胞）、HepG-2细胞（人肝癌细胞）、LU-1细胞（人肺腺癌细胞）以及MCF-7细胞（人乳腺癌细胞）。其中caseagrewifolin B（2）对KB和HepG-2细胞系具有抑制活性，半数抑制浓度（IC50）分别为6.2 μM和7.0 μM。以正常细胞NIH/3T3为对照进行测试时，相较于正常细胞，caseagrewifolin B（2）对癌细胞展现出显著的选择性抑制作用。caseanigrescen D（3）对4种癌细胞系均具有细胞毒性，但相较于正常细胞，其未表现出选择性抑制活性。