title: Polyamine-polycarboxylate metal complexes with different biological effectiveness as nitric oxide scavengers. Clues for drug design.
abstract: The synthesis of the Fe(III), Co(II), Mn(II), and Ru(III) complexes with two polyamine-polycarboxylate ligands, N-(2-hydroxyethyl)ethylenediamine-N, N', N'-triacetic acid (H3L1) and ethylene bisglycol tetraacetic acid (H4L2) is reported. Potentiometric studies showed that these ligands form stable complexes in aqueous solution and no metal release occurs, thus accounting for their low toxicity in cultured RAW 264.7 macrophages. X-ray characterization of the [Co(L1)](-) complex showed that binding sites are available at the metal for NO binding. Efficiency of these compounds to bind NO was studied by UV-vis spectrophotometry. Then their NO-scavenging properties were assayed in a cell-free system under physiological conditions, using S-nitroso-N-acetyl-D,L-penicillamine (SNAP) as NO source. The L1 complexes caused the most effective reduction of free NO, [Mn(L1)](-) being the most efficient. Conversely, in NOS II induced RAW 264.7 macrophages, the Ru(III) and Co(II) complexes with L2 were the most effective compounds. [Ru(L2)](-) also afforded significant protection against lipopolysaccharide-induced endotoxic shock in the mouse in vivo.
authors.affiliation: Department of Chemistry, University of Florence, Sesto Fiorentino, Florence, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Bambagioni
authors.forename: Daniele
authors.initials: D
authors.lastname: Bani
authors.forename: Andrea
authors.initials: A
authors.lastname: Bencini
authors.forename: Tarita
authors.initials: T
authors.lastname: Biver
authors.forename: Miriam
authors.initials: M
authors.lastname: Cantore
authors.forename: Riccardo
authors.initials: R
authors.lastname: Chelli
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Cinci
authors.forename: Paola
authors.initials: P
authors.lastname: Failli
authors.forename: Lisa
authors.initials: L
authors.lastname: Ghezzi
authors.forename: Claudia
authors.initials: C
authors.lastname: Giorgi
authors.forename: Silvia
authors.initials: S
authors.lastname: Nappini
authors.forename: Fernando
authors.initials: F
authors.lastname: Secco
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Tinè
authors.forename: Barbara
authors.initials: B
authors.lastname: Valtancoli
authors.forename: Marcella
authors.initials: M
authors.lastname: Venturini
mesh_terms: D000818:Animals; D002460:Cell Line; D002614:Chelating Agents / Q000737:chemistry* / Q000494:pharmacology; D003035:Cobalt; D018360:Crystallography, X-Ray; D004492:Edetic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000494:pharmacology; D007501:Iron; D008024:Ligands; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008345:Manganese; D051379:Mice; D008958:Models, Molecular; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000737:chemistry; D011199:Potentiometry; D012428:Ruthenium; D026423:S-Nitroso-N-Acetylpenicillamine / Q000494:pharmacology; D012769:Shock / Q000188:drug therapy; D013329:Structure-Activity Relationship
chemical_list: D002614:Chelating Agents; D008024:Ligands; D008070:Lipopolysaccharides; D020030:Nitric Oxide Donors; D009569:Nitric Oxide; D003035:Cobalt; D008345:Manganese; D004533:Egtazic Acid; D026423:S-Nitroso-N-Acetylpenicillamine; D012428:Ruthenium; D004492:Edetic Acid; D007501:Iron; C026060:N-(hydroxyethyl)ethylenediaminetriacetic acid