Two cyclic polyamine-polycarboxylate ligands, 1,4,7,10-tetraazacyclododecane-1,7-diacetic acid (H2L3) and 4,10-dimethyl-1,4,7,10-tetraazacyclododecane-1,7-diacetic acid (H2L4), and two noncyclic scaffolds, N-(2-hydroxyethyl)ethylenediamine-N,N0,N0-triacetic acid (H3L1) and ethylene-bisglycoltetracetic acid (H4L2), form stable complexes with Mn(II) in aqueous solutions. Cyclic voltammograms show that the complexes with the most hydrophobic ligands, [MnL2]2- and [MnL4], are oxidized at higher potential than [MnL1]- and [MnL3]. The pharmacological properties of these molecules were evaluated as superoxide ion scavengers and anti-inflammatory compounds. Among the four complexes, [MnL4] was the most bioactive, being effective in the nanomolar/micromolar range. It abates the levels of key markers of oxidative injury on cultured cells and ameliorates the outcome parameters in animal models of acute and chronic inflammation. [MnL4] toxicity was very low on both cell cultures in vitro and mice in vivo. Hence, we propose [MnL4] as a novel stable oxygen radical scavenging molecule, active at low doses and with a low toxicity.

A novel manganese complex effective as superoxide anion scavenger and therapeutic agent against cell and tissue oxidative injury / Failli P; Bani D; Cantore M; Di Cesare Mannelli L; Ghelardini C; Giorgi C; Innocenti M; Udisti R; Rugi F; Spepi A;Valtancoli B; Bencini A.. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - STAMPA. - 52:(2009), pp. 7273-7283. [10.1021/jm901298x]

A novel manganese complex effective as superoxide anion scavenger and therapeutic agent against cell and tissue oxidative injury.

FAILLI, PAOLA;BANI, DANIELE;DI CESARE MANNELLI, LORENZO;GHELARDINI, CARLA;GIORGI, CLAUDIA;INNOCENTI, MASSIMO;UDISTI, ROBERTO;RUGI, FRANCESCO;VALTANCOLI, BARBARA;BENCINI, ANDREA
2009

Abstract

Two cyclic polyamine-polycarboxylate ligands, 1,4,7,10-tetraazacyclododecane-1,7-diacetic acid (H2L3) and 4,10-dimethyl-1,4,7,10-tetraazacyclododecane-1,7-diacetic acid (H2L4), and two noncyclic scaffolds, N-(2-hydroxyethyl)ethylenediamine-N,N0,N0-triacetic acid (H3L1) and ethylene-bisglycoltetracetic acid (H4L2), form stable complexes with Mn(II) in aqueous solutions. Cyclic voltammograms show that the complexes with the most hydrophobic ligands, [MnL2]2- and [MnL4], are oxidized at higher potential than [MnL1]- and [MnL3]. The pharmacological properties of these molecules were evaluated as superoxide ion scavengers and anti-inflammatory compounds. Among the four complexes, [MnL4] was the most bioactive, being effective in the nanomolar/micromolar range. It abates the levels of key markers of oxidative injury on cultured cells and ameliorates the outcome parameters in animal models of acute and chronic inflammation. [MnL4] toxicity was very low on both cell cultures in vitro and mice in vivo. Hence, we propose [MnL4] as a novel stable oxygen radical scavenging molecule, active at low doses and with a low toxicity.
2009
52
7273
7283
Failli P; Bani D; Cantore M; Di Cesare Mannelli L; Ghelardini C; Giorgi C; Innocenti M; Udisti R; Rugi F; Spepi A;Valtancoli B; Bencini A.
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/366353
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