Phosphatidylinositol mannosides: synthesis and suppression of allergic airway disease.

Abstract

Phosphatidylinositol mannoside (PIM) extracts from mycobacteria have been shown previously to suppress allergic airway inflammation in mice. To help determine the structural requirements for activity, PIM1(2) (1), PIM1(6) (2) and PIM2 (3) were synthesized and tested for their ability to suppress cellular inflammation in a mouse model of allergic asthma. The synthetic PIMs were all effective in suppressing airway eosinophilia in the asthma model, with PIM1(6) being the most effective. Suppression of all inflammatory cells monitored was observed, indicating a general blockade of cellular inflammation. Non-mannosylated phosphatidylinositol (PI) had no suppressive effect, indicating that at least one alpha-d-mannopyranosyl residue is necessary for activity. The suppressive effect of the three PIM compounds indicates that other members of this set may be of value in treatment of a range of diseases driven by infiltration of inflammatory cells.

• Authors: Gary D Ainge, Jennifer Hudson, David S Larsen, Gavin F Painter, Gurmit Singh Gill, Jacquie L Harper
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 14 Issue 16 Pg. 5632-42 (Aug 15 2006) ISSN: 0968-0896 [Print] England
• PMID: 16697208 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Allergic Agents
• Phosphatidylinositols
• phosphatidylinositol mannoside

Topics

• Animals
• Anti-Allergic Agents (chemical synthesis, therapeutic use)
• Asthma (drug therapy)
• Inflammation (pathology)
• Mice
• Mice, Inbred C57BL
• Phosphatidylinositols (chemical synthesis, therapeutic use)
• Respiratory Hypersensitivity (drug therapy)
• Structure-Activity Relationship