Oxadiazole derivatives containing 1,4-benzodioxan as potential immunosuppressive agents against RAW264.7 cells

Bioorg Med Chem. 2011 Aug 15;19(16):4895-902. doi: 10.1016/j.bmc.2011.06.061. Epub 2011 Jun 28.

Abstract

A series of oxadiazole derivatives containing 1,4-benzodioxan (4a-4s) have been first synthesized for their potential immunosuppressive activity. Among the compounds, compound 4i showed the most potent biological activity against RAW264.7 cells (inhibition=37.66±2.34% for NO overproduction and IC(50)=0.05μM for iNOS). Docking simulation was performed to position compound 4i into the iNOS structure active site to determine the probable binding model. RT-PCR experiment results demonstrated that some of these compounds possessed good immunosuppressive activity against iNOS, especially for compound 4i. Therefore, compound 4i with potent inhibitory activity may be a potential agent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Catalytic Domain
  • Cell Line
  • Dioxanes / chemistry*
  • Drug Evaluation, Preclinical
  • Humans
  • Immunosuppressive Agents / chemical synthesis*
  • Immunosuppressive Agents / chemistry
  • Immunosuppressive Agents / pharmacology
  • Macrophages / drug effects
  • Mice
  • Models, Molecular
  • Molecular Conformation
  • Nitric Oxide / analysis
  • Nitric Oxide / antagonists & inhibitors
  • Nitric Oxide / biosynthesis
  • Nitric Oxide Synthase Type II / analysis
  • Nitric Oxide Synthase Type II / antagonists & inhibitors
  • Oxadiazoles / chemical synthesis*
  • Oxadiazoles / chemistry
  • Oxadiazoles / pharmacology
  • Protein Binding
  • Structure-Activity Relationship

Substances

  • Dioxanes
  • Immunosuppressive Agents
  • Oxadiazoles
  • Nitric Oxide
  • Nitric Oxide Synthase Type II
  • 1,4-benzodioxan