Ma Chao-Mei, Cai Shao-Qing, Cui Jing-Rong, Wang Rui-Qing, Tu Peng-Fei, Hattori Masao, Daneshtalab Mohsen
School of Pharmaceutical Sciences, Peking University, No. 38 Xueyuan Road, Haidian District, Beijing 100083, China.
Eur J Med Chem. 2005 Jun;40(6):582-9. doi: 10.1016/j.ejmech.2005.01.001.
Ursolic acid and 2alpha-hydroxyursolic acid isolated from apple peels were found to show growth inhibitory activity against four tumor cell lines, HL-60, BGC, Bel-7402 and Hela. Structural modifications were performed on the C-3, C-28 and C-11 positions of ursolic acid and the cytotoxicity of the derivatives was evaluated. The SAR revealed that the triterpenes possessing two hydrogen-bond forming groups (an H-donor and a carbonyl group) at positions 3 and 28 exhibit cytotoxic activity. The configuration at C-3 was found to be important for the activity. Introduction of an amino group increased the cytotoxicity greatly. A 3beta-amino derivative was 20 times more potent than the parent ursolic acid. The 28-aminoalkyl dimer compounds showed selective cytotoxicity.
从苹果皮中分离出的熊果酸和2α-羟基熊果酸对四种肿瘤细胞系HL-60、BGC、Bel-7402和Hela显示出生长抑制活性。对熊果酸的C-3、C-28和C-11位进行了结构修饰，并评估了衍生物的细胞毒性。构效关系研究表明，在3位和28位具有两个氢键形成基团（一个氢供体和一个羰基）的三萜类化合物具有细胞毒性活性。发现C-3位的构型对活性很重要。引入氨基大大增加了细胞毒性。一种3β-氨基衍生物的活性比母体熊果酸高20倍。28-氨基烷基二聚体化合物表现出选择性细胞毒性。
