Synthesis and antioxidant activity of new homocarnosine beta-cyclodextrin conjugates.
Several in vitro and in vivo studies have suggested that carnosine (beta-alanil-L-histidine) and homocarnosine (beta-aminobutyril-L-histidine) can act as scavengers of reactive oxygen species. beta-Cyclodextrin was functionalized with homocarnosine, obtaining the following new bioconjugate isomers: 6(A)-[(4-{[(1S)-1-carboxy-2-(1H-imidazol-4-yl)ethyl]amino}-4-oxobutyl)amino]-6(A)-deoxy-beta-cyclodextrin and (2(A)S,3(A)R)-3A-[(4-{[(1S)-1-carboxy-2-(1H-imidazol-4-yl)ethyl]amino}-4-oxobutyl)amino]-3(A)-deoxy-beta-cyclodextrin. Pulse radiolysis investigations show that the beta-cyclodextrin homocarnosine bioconjugates are scavengers of (*)OH radicals because of the formation of stable imidazole-centered radicals and the scavenger ability of glucose molecules of the macrocycle. The ability of these new beta-cyclodextrin derivatives to inhibit the copper(II) driven LDL oxidation was determined in comparison with that displayed by the analogous carnosine derivatives. Both the beta-cyclodextrin carnosine isomers show a higher protective effect than that of free dipeptide and homocarnosine derivatives, bringing into light the role of the beta-CD cavity. The ability of these new beta-cyclodextrin derivatives to inhibit the copper(II) driven LDL oxidation was determined in comparison with that displayed by the analogous carnosine derivatives. Both the beta-cyclodextrin carnosine isomers show a higher protective effect than that of free dipeptide and homocarnosine derivatives, bringing into light the role of the beta-CD cavity.
Amorini
Angela Maria
AM
Dipartimento di Scienze Chimiche, Università di Catania, V.le A. Doria 6, 95125 Catania, Italy.
Bellia
Francesco
F
Di Pietro
Valentina
V
Giardina
Bruno
B
La Mendola
Diego
D
Lazzarino
Giuseppe
G
Sortino
Salvatore
S
Tavazzi
Barbara
B
Rizzarelli
Enrico
E
Vecchio
Graziella
G
D000975:Antioxidants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002336:Carnosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007093:Imidazoles / Q000737:chemistry* / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010084:Oxidation-Reduction / Q000187:drug effects; D047392:beta-Cyclodextrins / Q000737:chemistry* / Q000494:pharmacology*
C522581:6(A)-((4-(((1S)-1-carboxy-2-(1H-imidazol-4-yl)ethyl)amino)-4-oxobutyl)amino)-6(A)-deoxy-beta-cyclodextrin; D000975:Antioxidants; D007093:Imidazoles; D008077:Lipoproteins, LDL; D047392:beta-Cyclodextrins; C005038:homocarnosine; D002336:Carnosine; C031215:betadex