EVALUATION OF POLYMERIC HYDROXAMIC ACID IRON CHELATORS FOR TREATMENT OF IRON OVERLOAD

  • 1 January 1985
    • journal article
    • research article
    • Vol. 232  (3) , 644-649
Abstract
A series of polymers bearing hydroxamic acid-terminated side chains were prepared for the purpose of developing new Fe chelators for treating Fe overload in .beta.-thalassemia (Cooley''s anemia) and other Fe diseases. The polymers are for the most part amino acid amide derivatives of acrylic and methacrylic acid with the terminal carboxyl group converted to the hydroxamic acid. The polymers are generally water soluble and sequester Fe(III) avidly. The polymeric Fe chelators were assayed via a mouse screen for activity in removing Fe. Fe overload mice were administered i.p. the Fe chelator over a 7 day period. Urine and feces were collected and the Fe content measured by atomic absorption. At the end of the treatment period the mice were sacrificed and the livers and spleens were homogenized and examined for Fe content. The results were compared with similar data obtained for the Fe chelator drug desferrioxamine as a standard. Four of the polymers prepared exhibited strong activity, as good or better than desferrioxamine in Fe removal capability. The 4 polymers are the polyacroloyl and polymethacryloyl derivatives of .beta.-alanine with the side chain carboxyls converted to the N''.sbd.H or N''.sbd.CH3 hydroxamic acids. Of these 4 the polyacryloyl N''.sbd.CH3 derivative exhibited superior behavior, being 3-5 times as effective as desferrioxamine at the lower dose level. None of the 4 polymers produced toxic signs and the administration was accompanied by little or no pain response.

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