Synthesis and effects of some novel tetrahydronaphthalene derivatives on proliferation and nitric oxide production in lipopolysaccharide activated Raw 264.7 macrophages

Eur J Med Chem. 2011 Feb;46(2):468-79. doi: 10.1016/j.ejmech.2010.11.021. Epub 2010 Nov 26.

Abstract

In this study, novel N-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalene-2-yl)-carboxamide (6-15) and 5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalene-2-carboxamide (16-32) derivatives were synthesized and their in vitro effects at 5 μM and 50 μM concentrations on proliferation and nitric oxide (NO*) production in lipopolysaccharide (LPS) activated RAW 264.7 macrophage cells were determined. Compounds 12, 17, 24 and 26 were found to decrease nitrite levels in a dose-dependent manner in LPS-activated cells. At the tested concentrations, these compounds did not exhibit cytotoxic effects. Interestingly, compound 27 which contains nitroxide free radical was the most active compound in this series showing 59.2% nitrite inhibition in LPS-activated macrophage cells.

MeSH terms

  • Animals
  • Cell Line
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Lipopolysaccharides / pharmacology
  • Macrophage Activation / drug effects*
  • Macrophages / drug effects*
  • Macrophages / metabolism
  • Mice
  • Molecular Structure
  • Nitric Oxide / biosynthesis*
  • Stereoisomerism
  • Structure-Activity Relationship
  • Tetrahydronaphthalenes / chemical synthesis*
  • Tetrahydronaphthalenes / chemistry
  • Tetrahydronaphthalenes / pharmacology*

Substances

  • Lipopolysaccharides
  • Tetrahydronaphthalenes
  • Nitric Oxide