Synthesis, chemical and biological studies on new Fe3+-glycosilated β-diketo complexes for the treatment of iron deficiency

A simple synthetic pathway to obtain glycosilated b-diketo derivatives is proposed. These compounds show a good iron(III) affinity therefore we may suggest the use of their Fe3þ-complexes as oral iron supplements in the treatment of anaemia. The glycosilated compounds (6-GlcH, 6-GlcOH and 6-GlcOCH3) are characterized by means of spectroscopic (UV, 1H and 13C NMR) and potentiometric techniques; they have a good water solubility, are kinetically stable in physiological condition (t1/2 > 100 h) and show a low cytotoxicity also in high concentrations (IC50 > 400 mM). They are able to bind Fe3þ ion in acid condition (pHw2) forming complex species thermodynamically more stable than those of other ligands commonly used in the treatment of iron deficiency. The iron complexes show also a good kinetic stability both in acidic and physiological pH and have a good lypophilicity (log P > _0.7) that suggests an efficient gastrointestinal absorption in view of their possible use in oral therapy. In addition they demonstrate a poor affinity for competitive biological metal ion such as Ca2þ, and in particular 6-GlcOCH3 is able to inhibit lipid peroxidation.