Pteridine-2,4-diamine derivatives as radical scavengers and inhibitors of lipoxygenase that can possess anti-inflammatory properties
| Autor: | Eleni, Pontiki, Dimitra, Hadjipavlou-Litina, Alexandros, Patsilinakos, Trang M, Tran, Charles M, Marson |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Male
Animals Anti-Inflammatory Agents Binding Sites Colitis Diamines Disease Models Animal Edema Free Radical Scavengers Lipoxygenase Lipoxygenase Inhibitors Molecular Docking Simulation Protein Binding Protein Structure Tertiary Pteridines Rats Reactive Oxygen Species Soybeans Drug Discovery3003 Pharmaceutical Science Pharmacology Molecular Medicine Medicine (all) Article |
| Zdroj: | Future medicinal chemistry |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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