New glycosidic derivatives of histidine-containing dipeptides with antioxidant properties and resistant to carnosinase activity

被引：39

作者：

Bellia, Francesco ^{[1
]}

Amorini, Angela Maria ^{[1
]}

La Mendola, Diego ^{[2
]}

Vecchio, Graziella ^{[1
]}

Tavazzi, Barbara ^{[3
]}

Giardina, Bruno ^{[3
]}

Di Pietro, Valentina ^{[3
]}

Lazzarino, Giuseppe ^{[1
]}

Rizzarelli, Enrico ^{[1
]}

机构：

[1] Univ Catania, Dept Chem Sci, I-95125 Catania, Italy

[2] CNR, Inst Biostruct & Bioimaging, I-95125 Catania, Italy

[3] Univ Cattolica Sacro Cuore, Inst Biochem & Clin Biochem, I-00164 Rome, Italy

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2008年 / 43卷 / 02期

关键词：

carnosine; anserine; homocamosine; beta-cyclodextrin; antioxidant activity; neurodegeneration;

D O I：

10.1016/j.ejmech.2007.03.038

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Synthesis, antioxidant properties and resistance to camosinase hydrolysis of histidine-containing dipeptides are reported in this study. Carnosine (beta-alanyl-L-histidine), homocamosine (gamma-aminobutyryl-L-histidine) and anserine (beta-alanyl-3-methyl-L-histidine) were covalently derivatized with beta-cyclodextrin to form different OH- or NH-bound conjugates. Mass spectroscopic and H-1 NMR data were used to determine the structure and the purity of the various beta-cyclodextrin derivatives. The inhibitory effect towards oxidation of human LDL induced by Cu2+ ions, was estimated by measuring malondialdehyde formation as a function of increasing concentrations of these newly synthesized compounds (the beta-cyclodextrin-anserine conjugated in 3 had the highest antioxidant effect). All derivatives had higher antioxidant effects than those of the corresponding free histidine-containing dipeptides. Resistance to rat brain camosinase hydrolysis of the most active derivatives indicated that these compounds are good candidates for further studies in more complex cellular and animal models. Their possible applications for remedies in neurodegenerative disorders, such as Alzheimer's and Parkinson's diseases, are discussed. (c) 2007 Elsevier Masson SAS. All rights reserved.

引用

页码：373 / 380

页数：8

共 58 条

[11] Protection of neuronal cells against reactive oxygen species by carnosine and related compounds [J].