The synthesis and the physicochemical and biological characterization of a series of carnosine amides bearing on the amido group alkyl substituents endowed with different lipophilicity are described. All synthesized products display carnosine-like properties differentiating from the lead for their high serum stability. They are able to complex Cu2þ ions at physiological pH with the same stoichiometry as carnosine. The newly synthesized compounds display highly significant copper ion sequestering ability and are capable of protecting LDL from oxidation catalyzed by Cu2þ ions, the most active compounds being the most hydrophilic ones. All the synthesized amides show quite potent carnosine-like HNE quenching activity; in particular, 7d, the member of the series selected for this kind of study, is able to cross the blood-brain barrier (BBB) and to protect primary mouse hippocampal neurons against HNEinduced death. These products can be considered metabolically stable analogues of carnosine and are worthy of additional investigation as potential neuroprotective agents.

Synthesis, physico-chemical characterization, andbiological activities of new carnosine derivatives stablein human serum as potential neuroprotective agents

BERTINARIA, Massimo;ROLANDO, Barbara;GIORGIS, Marta;MONTANARO, GABRIELE;GUGLIELMO, Stefano;CARABELLI, Valentina;GAVELLO, DANIELA;DANIELE, Pier Giuseppe;FRUTTERO, Roberta;GASCO, Alberto
2011

Abstract

The synthesis and the physicochemical and biological characterization of a series of carnosine amides bearing on the amido group alkyl substituents endowed with different lipophilicity are described. All synthesized products display carnosine-like properties differentiating from the lead for their high serum stability. They are able to complex Cu2þ ions at physiological pH with the same stoichiometry as carnosine. The newly synthesized compounds display highly significant copper ion sequestering ability and are capable of protecting LDL from oxidation catalyzed by Cu2þ ions, the most active compounds being the most hydrophilic ones. All the synthesized amides show quite potent carnosine-like HNE quenching activity; in particular, 7d, the member of the series selected for this kind of study, is able to cross the blood-brain barrier (BBB) and to protect primary mouse hippocampal neurons against HNEinduced death. These products can be considered metabolically stable analogues of carnosine and are worthy of additional investigation as potential neuroprotective agents.
54
611
621
http://pubs.acs.org/jmc
carnosine; antioxidants; copper complexes; HNE-scavenging
Massimo Bertinaria; Barbara Rolando; Marta Giorgis; Gabriele Montanaro; Stefano Guglielmo; M. Federica Buonsanti; Valentina Carabelli; Daniela Gavello; Pier Giuseppe Daniele; Roberta Fruttero; Alberto Gasco
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/94458
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