A second-generation ferrocene-iminosugar hybrid with improved fucosidase binding properties

Bioorg Med Chem Lett. 2016 Mar 15;26(6):1546-1549. doi: 10.1016/j.bmcl.2016.02.017. Epub 2016 Feb 9.

Abstract

The synthesis and the biological evaluation of a new ferrocenyl-iminosugar conjugate designed for fucosidase inhibitory and anticancer activity is described. The compound showed strong affinity for fucosidase from bovine kidney (Ki=23 nM) and from Bacteroides thetaiotaomicron (Ki=150 nM), displaying a 10-fold tighter binding affinity for these enzymes than the previous analogs. The interaction pattern that improves binding has been evaluated through structural analysis of the inhibitor-enzyme complex. The ferrocenyl-iminosugar exhibits significant anticancer activity on MDA-MB-231 and SK-MEL28 cell lines at 100 μM.

Keywords: Anticancer; Ferrocene; Fucosidase; Iminosugars; Inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Bacteroides / enzymology
  • Binding Sites / drug effects
  • Cattle
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Ferrous Compounds / chemistry
  • Ferrous Compounds / pharmacology*
  • Humans
  • Imino Sugars / chemistry
  • Imino Sugars / pharmacology*
  • Kidney / enzymology
  • Metallocenes
  • Molecular Structure
  • Structure-Activity Relationship
  • alpha-L-Fucosidase / antagonists & inhibitors*
  • alpha-L-Fucosidase / metabolism

Substances

  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Ferrous Compounds
  • Imino Sugars
  • Metallocenes
  • alpha-L-Fucosidase
  • ferrocene