Stachybotrydial, a potent inhibitor of fucosyltransferase and sialyltransferase
- 作者：Lin ; Tzu-Wen ; Chang ; Wei-Wei ; Chen ; Chien-Chih ; Tsai ; Ying-Chieh
- 刊名：Biochemical and Biophysical Research Communications
- 出版年：2005
- 期刊代码：159_0006291x
- 类别：bio
- 出版时间：June 17, 2005
- 卷：331
- 期：4
- 页码：953-957
- 文件大小：157 K
摘要
Elevated expression of fucosylated glycoconjugates and fucosyltransferases (Fuc-Ts) is found in various tumor cells and has been correlated with aspects of tumor progression such as cell adhesion and metastasis. Thus, fucosyltransferase inhibitors are potentially useful as anti-tumor agents. In the present study, three known spirocyclic drimanes (1, 2, and 3) were isolated from the culture broth of the fungus Stachybotrys cylindrospora. Compound 1 (stachybotrydial) exhibits potent inhibitory activity against α1,3-fucosyltransferase (Fuc-TV) during screening, while compounds 2 and 3 show no such inhibitory activity. Kinetic analysis indicates that compound 1 is an uncompetitive inhibitor with respect to GDP-fucose and a noncompetitive inhibitor with respect to N-acetyllactosamine with Ki values of 10.7 and 9.7 μM, respectively. In addition, all three compounds also possess inhibitory activity against sialyltransferase (ST) but not against β1,4-galactosyltransferase. These observations provide novel chemical structure information that will help in the design of novel Fuc-T and ST inhibitors.