Discovery of novel indole derivatives as allosteric inhibitors of fructose-1,6-bisphosphatase

Eur J Med Chem. 2015 Jan 27:90:394-405. doi: 10.1016/j.ejmech.2014.11.049. Epub 2014 Nov 25.

Abstract

A series of novel indole derivatives was designed and synthesized as inhibitors of fructose-1,6-bisphosphatase (FBPase). The most potent compound 14c was identified with an IC50 value of 0.10 μM by testing the inhibitory activity against recombinant human FBPase. The structure-activity relationships were investigated on the substitution at 4- and 5-position of the indole scaffold. The binding interactions of the title compounds at AMP binding site of FBPase were predicted using CDOCKER algorithm.

Keywords: Allosteric inhibitor; Diabetes; Fructose-1,6-bisphosphatase inhibitor; Indole derivative.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allosteric Regulation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Discovery*
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Fructose-Bisphosphatase / antagonists & inhibitors*
  • Fructose-Bisphosphatase / metabolism
  • Humans
  • Indoles / chemical synthesis
  • Indoles / chemistry
  • Indoles / pharmacology*
  • Models, Molecular
  • Molecular Structure
  • Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • Indoles
  • Fructose-Bisphosphatase