Synthesis and in silico studies of novel sulfonamides having oxadiazole ring: As β-glucuronidase inhibitors

Bioorg Chem. 2017 Apr:71:86-96. doi: 10.1016/j.bioorg.2017.01.015. Epub 2017 Jan 26.

Abstract

Novel sulfonamides having oxadiazole ring were synthesized by multistep reaction and evaluated to check in vitro β-glucuronidase inhibitory activity. Luckily, except compound 13, all compounds were found to demonstrate good inhibitory activity in the range of IC50=2.40±0.01-58.06±1.60μM when compared to the standard d-saccharic acid 1,4-lactone (IC50=48.4±1.25μM). Structure activity relationship was also presented. However, in order to ensure the SAR as well as the molecular interactions of compounds with the active site of enzyme, molecular docking studies on most active compounds 19, 16, 4 and 6 was carried out. All derivatives were fully characterized by 1H NMR, 13C NMR and EI-MS spectroscopic techniques. CHN analysis was also presented.

Keywords: In silico; In vitro; Oxadiazole; Sulfonamides; Synthesis; β-Glucuronidase inhibitory activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • Glucuronidase / antagonists & inhibitors*
  • Glucuronidase / metabolism
  • Humans
  • Molecular Docking Simulation
  • Oxadiazoles / chemical synthesis
  • Oxadiazoles / chemistry*
  • Oxadiazoles / pharmacology*
  • Structure-Activity Relationship
  • Sulfonamides / chemical synthesis
  • Sulfonamides / chemistry*
  • Sulfonamides / pharmacology*

Substances

  • Enzyme Inhibitors
  • Oxadiazoles
  • Sulfonamides
  • Glucuronidase