Biologically significant physico-chemical properties of antioxidative prostaglandin derivatives.
A monomeric derivative and several oligomeric derivatives were synthesized from prostaglandin B2. Their lipid solubility was studied by measuring their octanol-water partition coefficients. With EPR spectroscopy, the oligomeric derivatives were shown to have g = 2 signal, indicating these compounds have intrinsic free radicals. Measuring the rate of adenochrome formation, it was shown that these derivatives could scavenge superoxide anions. Using a spin-trapping technique employing DMPO, we found that these oligomers could also scavenge hydroxyl radicals. The calcium chelating activity of these compounds were also studied. In an in vitro rat model, these compounds inhibited lipid peroxidation as measured by the production of thiobarbituric acid reacting substances. Other prostaglandin oligomeric derivatives synthesized from PGE1 were also studied, and their properties were compared with these new compounds. Results suggest that both the water solubility and the chelating activity for calcium ions may not be related to their protective effects in ischemic or traumatic injury.
Ohnishi
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Philadelphia Biomedical Research Institute, King of Prussia, PA.
Ohnishi
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D000527:Alprostadil / Q000031:analogs & derivatives*; D000818:Animals; D000975:Antioxidants / Q000737:chemistry*; D002118:Calcium / Q000737:chemistry; D002462:Cell Membrane / Q000187:drug effects; D002614:Chelating Agents / Q000737:chemistry; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004578:Electron Spin Resonance Spectroscopy; D016166:Free Radical Scavengers; D006900:Hydroxylation; D007928:Lethal Dose 50; D008055:Lipids; D051379:Mice; D009391:Nephelometry and Turbidimetry; D000442:Octanols; D011453:Prostaglandins / Q000737:chemistry / Q000633:toxicity; D011456:Prostaglandins B / Q000737:chemistry; D011465:Prostaglandins, Synthetic / Q000737:chemistry*; D012995:Solubility; D013481:Superoxides; D014867:Water
D000975:Antioxidants; D002614:Chelating Agents; D016166:Free Radical Scavengers; D008055:Lipids; D000442:Octanols; D011453:Prostaglandins; D011456:Prostaglandins B; D011465:Prostaglandins, Synthetic; D014867:Water; D013481:Superoxides; C060277:MR 256; C060276:MR 356; D000527:Alprostadil; D002118:Calcium