Synthesis, Physicochemical Characterization, and Biological Activities of New Carnosine Derivatives Stable in Human Serum As Potential Neuroprotective Agents

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• 作者：Massimo Bertinaria ; Barbara Rolando ; Marta Giorgis ; Gabriele Montanaro ; Stefano Guglielmo ; M. Federica Buonsanti ; Valentina Carabelli ; Daniela Gavello ; Pier Giuseppe Daniele ; Roberta Fruttero ; Alberto Gasco
• 刊名：Journal of Medicinal Chemistry
• 出版年：2011
• 出版时间：January 27, 2011
• 年：2011
• 卷：54
• 期：2
• 页码：611-621
• 全文大小：904K
• 年卷期：v.54,no.2(January 27, 2011)
• ISSN：1520-4804

文摘

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 Cu²⁺ 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 Cu²⁺ 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鈭抌rain barrier (BBB) and to protect primary mouse hippocampal neurons against HNE-induced death. These products can be considered metabolically stable analogues of carnosine and are worthy of additional investigation as potential neuroprotective agents.