Design, synthesis and activity of benzothiazole-based inhibitors of NO production in LPS-activated macrophages

Bioorg Med Chem Lett. 2010 Nov 1;20(21):6199-202. doi: 10.1016/j.bmcl.2010.08.112. Epub 2010 Sep 16.

Abstract

Series of benzothiazoles were synthesized and evaluated their inhibitory activities for NO production in lipopolysaccharide-activated macrophages. The most potent compound was the indole-containing benzothiazole 3c with 4.18μM of IC(50). The mechanistic study suggested that benzothiazoles inhibited NO production by the suppression of iNOS protein and mRNA expression. They also suppressed the expression of COX-2 through the NF-κB inactivation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzothiazoles / chemical synthesis*
  • Benzothiazoles / pharmacology*
  • Blotting, Western
  • Cell Line
  • Cyclooxygenase 2 Inhibitors / chemical synthesis
  • Cyclooxygenase 2 Inhibitors / pharmacology
  • Drug Design
  • Enzyme Inhibitors / pharmacology*
  • Lipopolysaccharides / pharmacology*
  • Macrophages / drug effects*
  • Macrophages / metabolism*
  • Mass Spectrometry
  • Mice
  • NF-kappa B / antagonists & inhibitors
  • Nitric Oxide / antagonists & inhibitors*
  • Nitric Oxide / biosynthesis*
  • Nitric Oxide Synthase Type II / antagonists & inhibitors*
  • Nitric Oxide Synthase Type II / metabolism
  • RNA, Messenger / biosynthesis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Structure-Activity Relationship
  • Transcription Factor RelA / antagonists & inhibitors
  • Transcription Factor RelA / metabolism

Substances

  • Benzothiazoles
  • Cyclooxygenase 2 Inhibitors
  • Enzyme Inhibitors
  • Lipopolysaccharides
  • NF-kappa B
  • RNA, Messenger
  • Transcription Factor RelA
  • Nitric Oxide
  • Nitric Oxide Synthase Type II