Evaluation of polymeric hydroxamic acid iron chelators for treatment of iron overload. 1985

A Winston, and D V Varaprasad, and J J Metterville, and H Rosenkrantz

A series of polymers bearing hydroxamic acid-terminated side chains were prepared for the purpose of developing new iron chelators for treating iron overload in beta-thalassemia (Cooley's anemia) and other iron 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 iron(III) avidly. The polymeric iron chelators were assayed via a mouse screen for activity in removing iron. Iron overloaded mice were administered i.p. the iron chelator over a 7-day period. Urine and feces were collected and the iron 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 iron content. The results were compared with similar data obtained for the iron chelator drug desferrioxamine as a standard. Four of the polymers prepared exhibited strong activity, as good or better than desferrioxamine in iron removal capability. The four polymers are the polyacroloyl and polymethacryloyl derivatives of beta-alanine with the side chain carboxyls converted to the N'--H or N'--CH3 hydroxamic acids. Of these four the polyacryloyl N'--CH3 derivative exhibited superior behavior, being 3 to 5 times as effective as desferrioxamine at the lower dose level. None of the four polymers produced toxic signs and the administration was accompanied by little or no pain response.

UI MeSH Term Description Entries
D007501 Iron A metallic element with atomic symbol Fe, atomic number 26, and atomic weight 55.85. It is an essential constituent of HEMOGLOBINS; CYTOCHROMES; and IRON-BINDING PROTEINS. It plays a role in cellular redox reactions and in the transport of OXYGEN. Iron-56,Iron 56
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008297 Male Males
D011108 Polymers Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., BIOPOLYMERS; PLASTICS). Polymer
D002614 Chelating Agents Chemicals that bind to and remove ions from solutions. Many chelating agents function through the formation of COORDINATION COMPLEXES with METALS. Chelating Agent,Chelator,Complexons,Metal Antagonists,Chelators,Metal Chelating Agents,Agent, Chelating,Agents, Chelating,Agents, Metal Chelating,Antagonists, Metal,Chelating Agents, Metal
D002621 Chemistry A basic science concerned with the composition, structure, and properties of matter; and the reactions that occur between substances and the associated energy exchange.
D004285 Dogs The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065) Canis familiaris,Dog
D006877 Hydroxamic Acids A class of weak acids with the general formula R-CONHOH. Hydroxamic Acid,Acid, Hydroxamic,Acids, Hydroxamic
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013154 Spleen An encapsulated lymphatic organ through which venous blood filters.

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