Novel 21-amino steroids as potent inhibitors of iron-dependent lipid peroxidation.

摘要: Two representative compounds from a novel chemical series of potent inhibitors lipid peroxidation are described. The 21-[4-(2,6-di-1-pyrrolidinyl-4-pyrimidinyl)-1-piperazinyl]-16 alpha-methylpregna-1,4,9(11)-triene-3,20-dione monomethane sulfonate (U74006F) and 21-[4-(3,6-bis(diethylamino)-2-pyridinyl)-1-piperazinyl]-16 alpha-methylpregna-1,4,9(11)triene-3,20-dione hydrochloride (U74500A) inhibited in brain homogenates purified synaptosomes under variety conditions involving iron. With IC50 values ranging 2 to 60 microM, U74006F U74500A were comparable potency alpha-tocopherol or butylated hydroxytoluene nearly 100 times as desferrioxamine. Some specificity for intact phospholipid membranes is suggested since the ability inhibit was greatly reduced methanol solutions arachidonic acid. Despite close similarities their structures, response increasing concentrations Fe2+ assays differed qualitatively. One compounds, U74500A, may act membrane localized chelator