Benzothiazolium compounds: novel classes of inhibitors that suppress the nitric oxide production in RAW264.7 cells stimulated by LPS/IFNgamma

Bioorg Med Chem Lett. 2005 Apr 15;15(8):2027-32. doi: 10.1016/j.bmcl.2005.02.063.

Abstract

A series of benzothiazolium compounds were identified as novel classes of inhibitors of nitric oxide production in a cell culture system. They exhibited approximately 1600 folds potency with IC(50) at approximately 50nM to several microM as compared to IC(50) 88.4microM of l-NMMA, a known inhibitor of nitric oxide synthase. The mechanistic studies suggest that decreased iNOS protein synthesis and mRNA transcription, at least in part, were related to the inhibitory activity of effective benzothiazolium compounds. The correlation of in vivo and in vitro activities using mouse paw edema model was also demonstrated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzothiazoles
  • Cell Line, Tumor
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Interferon-gamma / antagonists & inhibitors
  • Interferon-gamma / pharmacology*
  • Lipopolysaccharides / antagonists & inhibitors
  • Lipopolysaccharides / pharmacology*
  • Mice
  • Nitric Oxide / antagonists & inhibitors*
  • Nitric Oxide / biosynthesis
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase / biosynthesis
  • Nitric Oxide Synthase Type II
  • Thiazoles / chemistry*
  • Thiazoles / pharmacology

Substances

  • Benzothiazoles
  • Enzyme Inhibitors
  • Lipopolysaccharides
  • Thiazoles
  • Nitric Oxide
  • Interferon-gamma
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • benzothiazole