Synthetic lactulose amines: novel class of anticancer agents that induce tumor-cell apoptosis and inhibit galectin-mediated homotypic cell aggregation and endothelial cell morphogenesis

Glycobiology. 2006 Mar;16(3):210-20. doi: 10.1093/glycob/cwj056. Epub 2005 Nov 10.


Galectins, a family of structurally related carbohydrate-binding proteins, contribute to different events associated with cancer biology, including apoptosis, homotypic cell aggregation, angiogenesis and tumor-immune escape. To interfere with galectin-carbohydrate interactions during tumor progression, a current challenge is the design of specific galectin inhibitors for therapeutic purposes. Here, we report the synthesis of three novel low molecular weight synthetic lactulose amines (SLA): (1) N-lactulose-octamethylenediamine (LDO), (2) N,N'-dilactulose-octamethylenediamine (D-LDO), and (3) N,N'-dilactulose-dodecamethylenediamine (D-LDD). These compounds showed a differential ability to inhibit binding of galectin-1 and/or galectin-3 to the highly glycosylated protein 90K in solid-phase assays. In addition, each compound demonstrated selective regulatory effects in different events linked to tumor progression including tumor-cell apoptosis, homotypic cell aggregation, and endothelial cell morphogenesis. Our results suggest that galectin inhibitors with subtle differences in their carbohydrate structures may be potentially used to specifically block different steps of tumor growth and metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amines / blood
  • Amines / chemical synthesis*
  • Amines / chemistry
  • Amines / pharmacology*
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / classification
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects*
  • Cell Aggregation / drug effects
  • Cell Shape / drug effects
  • Cells, Cultured
  • Endothelial Cells / cytology
  • Endothelial Cells / drug effects*
  • Galectins / antagonists & inhibitors*
  • Galectins / pharmacology
  • Glycosylation
  • Humans
  • Lactulose / chemistry*
  • Molecular Structure


  • Amines
  • Antineoplastic Agents
  • Galectins
  • Lactulose