Pteridine-2,4-diamine derivatives as radical scavengers and inhibitors of lipoxygenase that can possess anti-inflammatory properties.

Abstract

BACKGROUND:

Reactive oxygen species are associated with inflammation implicated in cancer, atherosclerosis and autoimmune diseases. The complex nature of inflammation and of oxidative stress suggests that dual-target agents may be effective in combating diseases involving reactive oxygen species.

RESULTS:

A novel series of N-substituted 2,4-diaminopteridines has been synthesized and evaluated as antioxidants in several assays. Many exhibited potent lipid antioxidant properties, and some are inhibitors of soybean lipoxygenase, IC50 values extending down to 100 nM for both targets. Several pteridine derivatives showed efficacy at 0.01 mmol/kg with little tissue damage in a rat model of colitis. 2-(4-methylpiperazin-1-yl)-N-(thiophen-2-ylmethyl)pteridin-4-amine (18f) at 0.01 mmol/kg exhibited potent anti-inflammatory activity (reduction by 41%).

CONCLUSION:

The 2,4-diaminopteridine core represents a new scaffold for lipoxygenase inhibition as well as sustaining anti-inflammatory properties.

• Authors: Eleni Pontiki, Dimitra Hadjipavlou-Litina, Alexandros Patsilinakos, Trang M Tran, Charles M Marson
• Journal: Future medicinal chemistry (Future Med Chem) Vol. 7 Issue 14 Pg. 1937-51 ( 2015) ISSN: 1756-8927 [Electronic] England
• PMID: 26423719 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 2,4-diaminopteridine
• Anti-Inflammatory Agents
• Diamines
• Free Radical Scavengers
• Lipoxygenase Inhibitors
• Pteridines
• Reactive Oxygen Species
• Lipoxygenase

Topics

• Animals
• Anti-Inflammatory Agents (chemistry, metabolism, therapeutic use)
• Binding Sites
• Colitis (drug therapy, pathology)
• Diamines (chemistry)
• Disease Models, Animal
• Edema (pathology, prevention & control)
• Free Radical Scavengers (chemistry, metabolism)
• Lipoxygenase (chemistry, metabolism)
• Lipoxygenase Inhibitors (chemistry, metabolism, therapeutic use)
• Male
• Molecular Docking Simulation
• Protein Binding
• Protein Structure, Tertiary
• Pteridines (chemistry, metabolism, therapeutic use)
• Rats
• Reactive Oxygen Species (chemistry, metabolism)
• Soybeans (enzymology)