Novel 2,5-disubtituted-1,3,4-oxadiazoles with benzimidazole backbone: a new class of β-glucuronidase inhibitors and in silico studies

Bioorg Med Chem. 2015 Jul 1;23(13):3119-25. doi: 10.1016/j.bmc.2015.04.081. Epub 2015 May 6.

Abstract

A library of novel 2,5-disubtituted-1,3,4-oxadiazoles with benzimidazole backbone (3a-3r) was synthesized and evaluated for their potential as β-glucuronidase inhibitors. Several compounds such as 3a-3d, 3e-3j, 3l-3o, 3q and 3r showed excellent inhibitory potentials much better than the standard (IC50=48.4±1.25μM: d-saccharic acid 1,4-lactone). All the synthesized compounds were characterized satisfactorily by using different spectroscopic methods. We further evaluated the interaction of the active compounds and the enzyme active site with the help of docking studies.

Keywords: Benzimidazole; In silico studies; Oxadiazole; β-Glucuronidase activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzimidazoles / chemical synthesis*
  • Benzimidazoles / chemistry
  • Catalytic Domain
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Glucuronidase / antagonists & inhibitors*
  • Glucuronidase / chemistry
  • Humans
  • Molecular Docking Simulation
  • Oxadiazoles / chemical synthesis*
  • Oxadiazoles / chemistry
  • Protein Binding
  • Structure-Activity Relationship

Substances

  • Benzimidazoles
  • Enzyme Inhibitors
  • Oxadiazoles
  • Glucuronidase