Evaluation of hydroxypyridinecarboxylic acids as new possible chelating agents for aluminium: solution chemistry, cytotoxicity, octanol/water partitioning, and chelation efficiency

Chelation therapy is the most efficient therapeutic approach for metal ion overload [1]. The chelators presently used for Al overload therapies, desferal and deferiprone, have several drawbacks. A multidisciplinary search for alternative molecules is being actively pursued [1-5]. We proposed some hydroxy-pyridine-carboxylic acids (HP) ([6] and references therein) as potential chelating agents for Al, as they have several requirements for an ideal chelator [3]. They have negligible or low toxicity, high stability of the Al(III) complexes at physiological conditions, low affinity towards essential metal ions to reduce undesired metal depletion, low molecular mass (less than 400 Dalton) to allow oral administration, no redox activity in vivo, and their Al(III) complex at physiological pH are hydrophilic so to enhance metal ion urinary elimination. In the present poster, the following results of several HP derivatives will be reported: Al(III)/HP solution chemistry, cytotoxicity, octanol/water partitioning, and chelation efficiency. 1. C. Hershko (Guest Editor), Sem. Hematol. 2005, 42, Issue 2, Supplement 1 2. M. J. Cunningham and D. G. Nathan, Curr. Opin. Hematol., 2005, 12, 129. 3. R. C. Hider and T. Zhou, Ann. N.Y. Acad. Sci., 2005, 1054, 141. 4. R. A. Yokel, Coord. Chem. Rev., 2002, 228, 97. 5. G. J. Kontoghiorghes, Drugs Fut., 2005, 30, 1241. 6. A. Dean, M. G. Ferlin, P. Brun, I. Castagliuolo, D. Badocco, P. Pastore, A. Venzo, G. G. Bombi and V. B. Di Marco, Dalton Trans., 2008, 1689.