Synthesis and Evaluation of the Analogues for Galactosyl Donors as Inhibitors of β-1,4-Galactosyltransferase

Abstract

The design and synthesis of analogs of galactosyl donors as potent and selective inhibitors of β-1,4-galactosyltransferase (β-1,4-GalT) are described. We employed a new strategy by incorporating 5-fluorouracil and an appropriate amino acid to galactose to prepare selective glycosyltransferase inhibitors. The in vitro cell assay showed that these compounds exhibited high cytotoxicity against the human leukemia cell line HL-60, human lung epithelial cell line A-549, and human liver cancer cell line BEL-7402, but low cytotoxicity against the murine leukemia cell line P388.

Keywords:

• Antitumor activity
• donor analog
• β-1,4-galactosyltransferase inhibitors
• synthesis

ACKNOWLEDGMENTS

We thank the Key International Cooperation Project of Ministry of Sciences and Technology, China (Grant No. 2008DFA31040) and National Basic Research Program (Grant No. 2003CB716403) for financial support. We also thank the National Center for Drug Screening in Shanghai Institute of Materia Medica, China, for biological testing.

Notes

^a No inhibitory rate at 100 µM.