Stachybotrydial, a potent inhibitor of fucosyltransferase and sialyltransferase.

Abstract

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 alpha1,3-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 microM, respectively. In addition, all three compounds also possess inhibitory activity against sialyltransferase (ST) but not against beta1,4-galactosyltransferase. These observations provide novel chemical structure information that will help in the design of novel Fuc-T and ST inhibitors.

• Authors: Tzu-Wen Lin, Wei-Wei Chang, Chien-Chih Chen, Ying-Chieh Tsai
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 331 Issue 4 Pg. 953-7 (Jun 17 2005) ISSN: 0006-291X [Print] United States
• PMID: 15882970 (Publication Type: Journal Article)

Chemical References

• Benzofurans
• Enzyme Inhibitors
• Spiro Compounds
• stachybotrydial
• Fucosyltransferases
• Sialyltransferases

Topics

• Benzofurans (pharmacology)
• Enzyme Inhibitors (pharmacology)
• Fucosyltransferases (antagonists & inhibitors)
• Kinetics
• Sialyltransferases (antagonists & inhibitors)
• Spiro Compounds (pharmacology)