Biological evaluation of sulfone derivatives as anti-inflammatory and tumor cells growth inhibitory agents

Int Immunopharmacol. 2006 Nov;6(11):1699-705. doi: 10.1016/j.intimp.2006.07.004. Epub 2006 Jul 31.

Abstract

A variety of sulfone derivatives including three dimethyl arylsulfonyl malonates (1-3), two bis-(arylethenesulfonyl)-vinyl benzenes (4 and 5) and a sulfone triazole (6) were evaluated for their anti-inflammatory as well as tumor cells growth inhibitory activities in vitro. The sulfone derivatives 1, 2, 3 and 6 significantly and dose-dependently inhibited the production of inflammatory mediators such as nitric oxide (NO), and cytokines (tumor necrosis factor (TNF)-alpha and interleukin (IL)-12), in lipopolysaccharide (LPS) and interferon (IFN)-gamma activated murine peritoneal macrophages, without displaying cytotoxicity. The inhibitory mechanism is found through reducing iNOS protein expression. In addition, the derivatives 1-3 significantly arrest mitogen-stimulated spleen cells in G0/G1 stage, whereas compounds 4-6 blocked the same in the G2/M phase. Furthermore, the sulfone derivatives 3 and 6 showed dramatically reduction in the ratio of IFN-gamma to IL-4 production from mitogen-stimulated spleen cells. On the other hand, the novel compounds exhibited interesting cytotoxic activities against a panel of cell lines, particularly, 20 muM of compound 3 showed 50% cytotoxic effect on human hepatoma cell line, but has no effect on normal human peripheral blood mononuclear cells. In conclusion, compound 3 showed interesting anti-inflammatory and tumor cells growth inhibitory functions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Antineoplastic Agents / pharmacology*
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Humans
  • Interferon-gamma / pharmacology
  • Interleukin-12 / antagonists & inhibitors
  • Interleukin-12 / metabolism
  • Leukocytes, Mononuclear / drug effects
  • Lipopolysaccharides / pharmacology
  • Macrophages, Peritoneal / drug effects*
  • Macrophages, Peritoneal / immunology
  • Macrophages, Peritoneal / metabolism
  • Malonates / pharmacology*
  • Mice
  • Mice, Inbred BALB C
  • Nitric Oxide / antagonists & inhibitors
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • Spleen / cytology
  • Spleen / immunology
  • Sulfones / chemistry
  • Sulfones / pharmacology*
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents
  • Antineoplastic Agents
  • Lipopolysaccharides
  • Malonates
  • Sulfones
  • Tumor Necrosis Factor-alpha
  • Interleukin-12
  • Nitric Oxide
  • Interferon-gamma
  • Nitric Oxide Synthase Type II