Stachybotrydial, a potent inhibitor of fucosyltransferase and sialyltransferase.
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.
Lin
Tzu-Wen
TW
Institute of Biochemistry, National Yang-Ming University, Taipei, Taiwan, ROC.
Chang
Wei-Wei
WW
Chen
Chien-Chih
CC
Tsai
Ying-Chieh
YC
D001572:Benzofurans / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005647:Fucosyltransferases / Q000037:antagonists & inhibitors*; D007700:Kinetics; D012799:Sialyltransferases / Q000037:antagonists & inhibitors*; D013141:Spiro Compounds / Q000494:pharmacology*
D001572:Benzofurans; D004791:Enzyme Inhibitors; D013141:Spiro Compounds; C094818:stachybotrydial; D005647:Fucosyltransferases; D012799:Sialyltransferases