Promising in Vitro anti-Alzheimer Properties for a Ruthenium(III) Complex

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• 作者：Luigi Messori ; Michela Camarri ; Teresa Ferraro ; Chiara Gabbiani ; Davide Franceschini
• 刊名：ACS Medicinal Chemistry Letters
• 出版年：2013
• 出版时间：March 14, 2013
• 年：2013
• 卷：4
• 期：3
• 页码：329-332
• 全文大小：286K
• 年卷期：v.4,no.3(March 14, 2013)
• ISSN：1948-5875

文摘

Metal complexes represent today an attractive class of experimental anti-Alzheimer agents with the potential of blocking 尾-amyloid 1鈥?2 aggregation and scavenging its toxicity. Three representative ruthenium(III) complexes, namely NAMI A, KP1019, and PMRU20, were specifically evaluated to this end in an established in vitro model of AD relying on primary cortical neurons. Notably, PMRU20 turned out to be highly effective in protecting cortical neurons against A尾 1鈥?2 toxicity, while the other tested ruthenium compounds were poorly active or even inactive; we also found that PMRU20 is virtually devoid of any significant toxicity in vitro at the applied concentrations. Interestingly, PMRU20 was neuroprotective even against the toxicity induced by A尾 25鈥?5. The direct reaction of PMRU20 with A尾 1鈥?2 was explored through ESI MS analysis and some adduct formation evidenced. In addition, thioflavin T assays revealed that PMRU20 greatly reduces A尾 1鈥?2 aggregation. The implications of these findings are discussed in relation to emerging treatment strategies for the Alzheimer鈥檚 disease.

Keywords:

Alzheimer鈥檚 disease; 尾-amyloid; ruthenium(III) complex