Potent anti-inflammatory activity of 3-aminovinylphosphonates as inhibitors of reactive oxygen intermediates, nitric oxides generation, and tumor necrosis factor-alpha release.
Two 3-aminoalkenylphosphonate compounds 1, 2, and a hydroxyl derivative, 2-(3-hydroxy-3-phenylpropyl)hex-1-enylphosphonate 3, recently synthesized in our lab, have been evaluated for their ability to modulate the production of reactive oxygen intermediates, nitric oxide (NO) and tumor necrosis factor (TNF-alpha) by murine macrophages. We found that all three molecules suppressed generation of reactive oxygen intermediates, NO, and TNF-alpha. However, although 2-(3-hydroxy-3-phenylpropyl)hex-1-enylphosphonate 3 possessed higher activity in suppression of reactive oxygen intermediates and nitric oxide compared to 3-aminoalkenylphosphonates 1 and 2, it showed less activity in the inhibition of tumor necrosis factor release.
Quntar
Abed Al Aziz Al
AA
Department of Medicinal Chemistry and Natural Products, School of Pharmacy, Faculty of Medicine, Hebrew University Jerusalem 91120, Israel.
Gallily
Ruth
R
Katzavian
Galia
G
Srebnik
Morris
M
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002460:Cell Line; D005260:Female; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D063065:Organophosphonates / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014753:Vinyl Compounds / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D063065:Organophosphonates; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D014753:Vinyl Compounds; D009569:Nitric Oxide