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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.

Two prostaglandin oligomeric compounds, an acid-form compound and an ester-form compound, were synthesized from alprostadil (prostaglandin E1). They were found to provide significant protection to the rat spinal cord against contusion injury. After laminectomy at the T-11 segment of the spinal cord, a weight drop (10 g x 5 cm) caused a "dynamic" injury. The degree of recovery was estimated by several neurologic deficit indices; the Tarlov score, inclined plane test and hot plate test. In the control group (no drug), animals were still paralyzed 4 weeks after injury (Tarlov score 1 to 2). By administering these prostaglandin oligomers, either pre-injury (30 min before injury; one dose of 6 mg/kg i.p.) or post-injury (3 doses, each of 6 mg/kg i.p. at 30 min, 6 h, and 12 h after injury), the Tarlov scores recovered to 3.5 to 4.5 by 4 weeks, and animals were able to either support body weight or to walk with a slight deficit. Although both acid- and ester-forms of the compound demonstrated efficacy, the ester-form provided greater protection to the spinal cord. Other neurologic deficit indices also supported these observations.