Synthesis and antioxidant activity of new homocarnosine β-cyclodextrin conjugates

Several in vitro and in vivo studies have suggested that carnosine (β-alanil-l-histidine) and homocarnosine (β-aminobutyril-l-histidine) can act as scavengers of reactive oxygen species. β-Cyclodextrin was functionalized with homocarnosine, obtaining the following new bioconjugate isomers: 6A-[(4-{[(1S)-1-carboxy-2-(1H-imidazol-4-yl)ethyl]amino}-4-oxobutyl)amino]-6A-deoxy-β-cyclodextrin and (2AS,3AR)-3A-[(4-{[(1S)-1-carboxy-2-(1H-imidazol-4-yl)ethyl]amino}-4-oxobutyl)amino]-3A-deoxy-β-cyclodextrin. Pulse radiolysis investigations show that the β-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 β-cyclodextrin derivatives to inhibit the copper(II) driven LDL oxidation was determined in comparison with that displayed by the analogous carnosine derivatives. Both the β-cyclodextrin carnosine isomers show a higher protective effect than that of free dipeptide and homocarnosine derivatives, bringing into light the role of the β-CD cavity.The ability of these new β-cyclodextrin derivatives to inhibit the copper(II) driven LDL oxidation was determined in comparison with that displayed by the analogous carnosine derivatives. Both the β-cyclodextrin carnosine isomers show a higher protective effect than that of free dipeptide and homocarnosine derivatives, bringing into light the role of the β-CD cavity.

Graphical abstractThe ability of new β-cyclodextrin homocarnosine conjugates to scavenger hydroxyl radicals and to inhibit LDL oxidation makes them promising agents against harmful oxygen species.Figure optionsDownload full-size imageDownload as PowerPoint slide