Representing an integration of basic and clinical sciences, this book focuses on new concepts in the design, synthesis, and testing of iron chelators for clinical application. It provides an overview of the pathophysiology of iron metabolism as it relates to the origins of iron-mediated tissue damage, and it clearly outlines successes and shortcomings of current iron chelation therapy in preventing such damage. The book also describes a number of other exciting potential therapeutic applications of iron chelators, such as in the treatment of malaria.
Other topics covered include iron coordination chemistry, recent advances in synthetic methods for accessing iron chelators, siderophore models, subcellular iron storage targets, and the possible application of biotechnology in the production of therapeutically useful iron chelators. The book also describes new animal models for evaluating chelators.
Table of Contents
Physiology and Pathophysiology of Iron Metabolism: Implications for Iron Chelation Therapy in Iron Overload (P. Ponka). Iron, Oxidative Damage and Chelating Agents (B. Halliwell). Iron Chelation Therapy in the Treatment of Iron Overload (M.J. Pippard). Potential Clinical Applications of Iron Chelating Therapy (C. Hershko, G. Link, M. Tzahor, and A. Pinson). Iron Withholding: The Natural Defense System and Its Modification by Pharmacologic Agents (E.D. Weinberg). Iron Chelation as a Chemotherapeutic Strategy in the Treatment of Malaria (V.R. Gordeuk, G.M. Brittenham, and P.E. Thuma). Towards Better Chelation Therapy: Current Concepts and Research Strategy (H.P. Schnebli, I. Hassan, K.O. Hamilton, S. Lynch, Y. Jin, H.P. Nick, H.H. Peter, U. Junker Walker, R. Ziel, S.C. Khanna, R. Dean, and R.J. Bergeron). Siderophores as Biological Deferration Agents and the Regulation of their Synthesis by Iron (J.B. Neilands). Biochemical and Genetic Studies on Lysine: N6-hydroxylase Involved in Aerobactin Synthesis (A.M. Thariath, M.A. Valvano, and T. Viswanatha). The Ferrichrome Biosynthetic Pathway of Ustilago maydis Reveals Similarities to the Aerobactin Pathway of Escherichia Coli and to Globin Gene Regulation in Erythroid Cells (S.A. Leong, B. Mei, C. Voisard, A. Budde, J. McEvoy, J. Wang, P. Xu, and B. Saville). Ability of Catecholate Derivatives to Promote Growth of Gram-Negative Bacteria (R. Reissbrodt and W. Rabsch). Synthesis and Biological Activity of Hydroxamate-Based Iron Chelators (R.J. Bergeron and J.S. McManis). Siderophore-Mediated Drug Delivery: The Design, Synthesis, and Study of Siderophore-Antibiotic and Antifungal Conjugates (M.J. Miller and F. Malouin). Siderophore-Based Hydroxypyridonate Sequestering Agents (K.N. Raymond and J. Xu). Ligand Design of Chelating Agents Effective in the Coordination of Fe(III) and for the Removal of Iron in Cases of Iron Overload (A.E. Martell, R.J. Motekaitis, Y. Sun, and E.T. Clarke). The Design of Therapeutically Useful Iron Chelators (R.C. Hider, J.B. Porter, and S. Singh). A Comparative Evaluation of Iron Chelators in a Primate Model (H.H. Peter, R.J. Bergeron, R.R. Streiff, and J. Wiegand). Preliminary Results from a Phase I Clinical Trial of HBED (R.W. Grady, A.D. Salbe, M.W. Hilgartner, and P.J. Giardina).