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Synthesis of New Carnosine Derivatives of β ‐Cyclodextrin and Their Hydroxyl Radical Scavenger Ability
Author(s) -
La Mendola Diego,
Sortino Salvatore,
Vecchio Graziella,
Rizzarelli Enrico
Publication year - 2002
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/1522-2675(200206)85:6<1633::aid-hlca1633>3.0.co;2-g
Subject(s) - chemistry , carnosine , scavenger , dipeptide , cyclodextrin , radical , radiolysis , imidazole , hydroxyl radical , lipophilicity , stereochemistry , amino acid , medicinal chemistry , organic chemistry , biochemistry
Several in vitro and in vivo studies have suggested that carnosine can act as a scavenger of reactive oxygen species and intracellular proton buffer. On the other hand, carnosinase is a specific peptidase able to destroy the biological active dipeptide. To overcome this constraint, β ‐cyclodextrin ( β ‐CD) was functionalized with carnosine to give the following new compounds: 6 A ‐[(3‐{[(1 S )‐1‐carboxy‐2‐(1 H ‐imidazol‐4‐yl)ethyl]amino}‐3‐oxopropyl)amino]‐6 A ‐deoxy‐ β ‐cyclodextrin ( 1 ), 6 A ‐[( β ‐alanyl‐ L ‐histidyl)amino]‐ β ‐cyclodextrin ( 2 ), and (2 A S ,3 A R )‐3 A ‐[(3‐{[(1 S )‐1‐carboxy‐2‐(1 H ‐imidazol‐4‐yl)ethyl]amino}‐3‐oxopropyl)amino]‐3 A ‐deoxy‐ β ‐cyclodextrin ( 3 ). Pulse‐radiolysis investigation showed that the β ‐CD derivatives 1 – 3 are excellent scavengers of OH . radicals. Their activity is not only due to the formation of the stable imidazole‐centered radical, but also to the scavenger ability of the glucose moieties of the macrocycle ( Scheme ). This effect is independent of the disposition of the imidazole ring. In fact, the quenching constant values are similar for the three compounds.