Fang Liqiong, Ito Aiko, Chai Hee-Byung, Mi Qiuwen, Jones William P, Madulid Domingo R, Oliveros Mildred B, Gao Qi, Orjala Jimmy, Farnsworth Norman R, Soejarto Djaja D, Cordell Geoffrey A, Swanson Steven M, Pezzuto John M, Kinghorn A Douglas
Program for Collaborative Research in the Pharmaceutical Sciences, and the Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, 60612, USA.
J Nat Prod. 2006 Mar;69(3):332-7. doi: 10.1021/np058083q.
Fractionation of an ethyl acetate-soluble extract of the stem bark of Dichapetalum gelonioides, collected in the Philippines, using the LNCaP (hormone-dependent human prostate) cell line as a monitor, led to the purification of three dichapetalin-type triterpenoids [dichapetalins A (1), I (2), and J (3)], along with two dolabrane norditerpenoids (6, 7), and the additional triterpenoids zeylanol (8), 28-hydroxyzeylanol (9), and betulinic acid. Since compounds 1-3 exhibited promising selectivity against the SW626 (human ovarian cancer) cell line, a re-collection of the plant material was carried out, to obtain more of these compounds for additional biological testing. Two further phenylpyranotriterpenoids [dichapetalins K (4) and L (5)] were isolated from the re-collected plant material. The structures of the new compounds 2-5 and 9 were determined on the basis of spectroscopic data interpretation, and the relative configuration of 6 was confirmed using X-ray crystallography. Compounds 4-6 and the methyl ester, 6a, exhibited broad cytotoxic activity when tested against a panel of human tumor cell lines. Dichapetalin A (1) was not active when evaluated in an in vivo hollow fiber assay in the dose range 1-6 mg/kg.
以菲律宾采集的 Dichapetalum gelonioides 茎皮的乙酸乙酯可溶提取物为原料，以 LNCaP（激素依赖性人前列腺）细胞系为监测指标进行分馏，得到了三种地茶素型三萜类化合物 [地茶素 A (1)、I (2) 和 J (3)]，以及两种多拉烷降二萜类化合物 (6, 7)，还有另外的三萜类化合物齐墩果醇 (8)、28 - 羟基齐墩果醇 (9) 和桦木酸。由于化合物 1 - 3 对 SW626（人卵巢癌）细胞系表现出有前景的选择性，因此重新采集了植物材料，以获取更多这些化合物用于进一步的生物学测试。从重新采集的植物材料中又分离出了另外两种苯基吡喃三萜类化合物 [地茶素 K (4) 和 L (5)]。新化合物 2 - 5 和 9 的结构通过光谱数据解析确定，6 的相对构型通过 X 射线晶体学得到证实。化合物 4 - 6 及其甲酯 6a 在针对一组人肿瘤细胞系进行测试时表现出广泛的细胞毒性活性。地茶素 A (1) 在 1 - 6 mg/kg 的剂量范围内进行体内中空纤维试验评估时没有活性。
