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.