Novel 2-[(benzylamino)methyl]pyrrolidine-3,4-diol derivatives as alpha-mannosidase inhibitors and with antitumor activities against hematological and solid malignancies

Bioorg Med Chem. 2010 May 1;18(9):3320-34. doi: 10.1016/j.bmc.2010.03.009. Epub 2010 Mar 9.

Abstract

Novel alpha-mannosidase inhibitors of the type (2R,3R,4S)-2-({[(1R)-2-hydroxy-1-arylethyl]amino}methyl)pyrrolidine-3,4-diol have been prepared and assayed for their anticancer activities. Compound 30 with the aryl group=4-trifluoromethylbiphenyl inhibits the proliferation of primary cells and cell lines of different origins, irrespective of Bcl-2 expression levels, inducing a G2/Mcell cycle arrest and by modification of genes involved in cell cycle progression and survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Hematologic Neoplasms*
  • Humans
  • Inhibitory Concentration 50
  • Molecular Structure
  • Neoplasms*
  • Teprotide* / chemical synthesis
  • Teprotide* / chemistry
  • Teprotide* / pharmacology
  • alpha-Mannosidase / antagonists & inhibitors*

Substances

  • Antineoplastic Agents
  • Teprotide
  • alpha-Mannosidase