Synthesis, chemical and biological studies on new Fe(3+)-glycosilated beta-diketo complexes for the treatment of iron deficiency.
A simple synthetic pathway to obtain glycosilated beta-diketo derivatives is proposed. These compounds show a good iron(III) affinity therefore we may suggest the use of their Fe(3+)-complexes as oral iron supplements in the treatment of anaemia. The glycosilated compounds (6-GlcH, 6-GlcOH and 6-GlcOCH(3)) are characterized by means of spectroscopic (UV, (1)H and (13)C NMR) and potentiometric techniques; they have a good water solubility, are kinetically stable in physiological condition (t(1/2)>100h) and show a low cytotoxicity also in high concentrations (IC(50)>400 microM). They are able to bind Fe(3+) ion in acid condition (pH approximately 2) 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 (logP>-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 Ca(2+), and in particular 6-GlcOCH(3) is able to inhibit lipid peroxidation.
Arezzini
Beatrice
B
Department of Physiopathology and Experimental Medicine, University of Siena, Via Aldo Moro 53100 Siena, Italy.
Ferrali
Marco
M
Ferrari
Erika
E
Frassineti
Chiara
C
Lazzari
Sandra
S
Marverti
Gaetano
G
Spagnolo
Ferdinando
F
Saladini
Monica
M
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D005290:Ferric Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006031:Glycosylation; D000090463:Iron Deficiencies; D007661:Ketoses / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D007700:Kinetics; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D013053:Spectrophotometry; D017186:Titrimetry; D014709:Vero Cells
D005290:Ferric Compounds; D007661:Ketoses; D008024:Ligands