Sturm S, Gil R R, Chai H B, Ngassapa O D, Santisuk T, Reutrakul V, Howe A, Moss M, Besterman J M, Yang S L, Farthing J E, Tait R M, Lewis J A, O'Neill M J, Farnsworth N R, Cordell G A, Pezzuto J M, Kinghorn A D
Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago 60612, USA.
J Nat Prod. 1996 Jul;59(7):658-63. doi: 10.1021/np960370u.
Chloroform-soluble extracts of the stems and of the mixed stems and stem bark of Lophopetalum wallichii were found to be inhibitory in a farnesyl protein transferase (FPTase) bioassay system. During the course of activity-guided fractionation, the known lupane-type triterpenes, ochraceolide A (1), ochraceolide B (2), betulin, and lupeol and the new lupane lactone, dihydro ochraceolide A (4), were isolated. The stereochemistry of the epoxide group of ochraceolide B (2) was determined by preparation of both epoxide isomers [2, and the new semisynthetic derivative, 20-epi-ochraceolide B (3)] from 1. The structure of 4 was established by reduction of 1 with sodium borohydride. Compounds 1 and 2 exhibited significant inhibitory activity in the FPTase assay (IC50 values of 1.0 and 0.7 microgram/mL, respectively). Lupeol was found to be weakly active (IC50 65.0 micrograms/mL) in this test system, whereas no significant inhibition was detected for betulin or compounds 3 or 4. When evaluated against a panel of human cancer cells in culture, compounds 1 and 4 were modestly cytotoxic. Compounds 2 and 3 were not active in the panel.
在法尼基蛋白转移酶（FPTase）生物测定系统中，发现了锡叶藤茎以及茎与茎皮混合物的氯仿可溶提取物具有抑制作用。在活性导向的分馏过程中，分离出了已知的羽扇豆烷型三萜类化合物，赭曲霉内酯A（1）、赭曲霉内酯B（2）、桦木醇和羽扇豆醇，以及新的羽扇豆烷内酯二氢赭曲霉内酯A（4）。通过从1制备两种环氧化物异构体[2和新的半合成衍生物20-表赭曲霉内酯B（3）]，确定了赭曲霉内酯B（2）环氧基团的立体化学。通过用硼氢化钠还原1确定了4的结构。化合物1和2在FPTase测定中表现出显著的抑制活性（IC50值分别为1.0和0.7微克/毫升）。在该测试系统中发现羽扇豆醇活性较弱（IC50为65.0微克/毫升），而未检测到桦木醇或化合物3和4有显著抑制作用。在针对一组培养的人类癌细胞进行评估时，化合物1和4具有适度的细胞毒性。化合物2和3在该组中无活性。
