Design, Synthesis, and Examination of Neuron Protective Properties of Alkenylated and Amidated Dehydro-Silybin Derivatives

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• 作者：Lei Xiang Yang ; Ke Xin Huang ; Hai Bo Li ; Jing Xu Gong ; Feng Wang ; Yu Bing Feng ; Qiao Feng Tao ; Yi Hang Wu ; Xiao Kun Li ; Xiu Mei Wu ; Su Zeng ; Shawn Spencer ; Yu Zhao ; Jia Qu
• 刊名：Journal of Medicinal Chemistry
• 出版年：2009
• 出版时间：December 10, 2009
• 年：2009
• 卷：52
• 期：23
• 页码：7732-7752
• 全文大小：1431K
• 年卷期：v.52,no.23(December 10, 2009)
• ISSN：1520-4804

文摘

A series of C7-O- and C20-O-amidated 2,3-dehydrosilybin (DHS) derivatives ((±)-1a−f and (±)-2), as well as a set of alkenylated DHS analogues ((±)-4a−f), were designed and de novo synthesized. A diesteric derivative of DHS ((±)-3) and two C23 esterified DHS analogues ((±)-5a and (±)-5b) were also prepared for comparison. The cell viability of PC12 cells, Fe²⁺ chelation, lipid peroxidation (LPO), free radical scavenging, and xanthine oxidase inhibition models were utilized to evaluate their antioxidative and neuron protective properties. The study revealed that the diether at C7−OH and C20−OH as well as the monoether at C7−OH, which possess aliphatic substituted acetamides, demonstrated more potent LPO inhibition and Fe²⁺ chelation compared to DHS and quercetin. Conversely, the diallyl ether at C7−OH and C20−OH was more potent in protection of PC12 cells against H₂O₂-induced injury than DHS and quercetin. Overall, the more lipophilic alkenylated DHS analogues were better performing neuroprotective agents than the acetamidated derivatives. The results in this study would be beneficial for optimizing the therapeutic potential of lignoflavonoids, especially in neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease.