title: Synthesis, chemical and biological studies on new Fe(3+)-glycosilated beta-diketo complexes for the treatment of iron deficiency.
abstract: 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.
authors.affiliation: Department of Physiopathology and Experimental Medicine, University of Siena, Via Aldo Moro 53100 Siena, Italy.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Arezzini
authors.forename: Marco
authors.initials: M
authors.lastname: Ferrali
authors.forename: Erika
authors.initials: E
authors.lastname: Ferrari
authors.forename: Chiara
authors.initials: C
authors.lastname: Frassineti
authors.forename: Sandra
authors.initials: S
authors.lastname: Lazzari
authors.forename: Gaetano
authors.initials: G
authors.lastname: Marverti
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Spagnolo
authors.forename: Monica
authors.initials: M
authors.lastname: Saladini
mesh_terms: 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
chemical_list: D005290:Ferric Compounds; D007661:Ketoses; D008024:Ligands