Ligustrazinyl amides: a novel class of ligustrazine-phenolic acid derivatives with neuroprotective effects

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• 作者：Guoliang Li ; Xin Xu ; Kuo Xu ; Fuhao Chu ; Jixiang Song…
• 关键词：Ligustrazine derivative ; Phenolic acid ; Neuroprotective effect ; PC12 cell
• 刊名：Chemistry Central Journal
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：9
• 期：1
• 全文大小：1,196 KB
• 参考文献：1. Lindvall, O, Kokaia, Z (2006) Stem cells for the treatment of neurological disorders. Nature 441: pp. 1094-6 CrossRef
  2. Yu, L, Wang, N, Zhang, Y, Wang, Y, Li, J, Wu, Q (2014) Neuroprotective effect of muscone on glutamate-induced apoptosis in PC12 cells via antioxidant and Ca2+ antagonism. Neurochem Int 70: pp. 10-21 CrossRef
  3. Feng, X, Liang, N, Zhu, D, Gao, Q, Peng, L, Dong, H (2013) Resveratrol inhibits β-amyloid-induced neuronal apoptosis through regulation of SIRT1-ROCK1 signaling pathway. PLoS One 8: pp. e59888 CrossRef
  4. Tereshchenko, J, Maddalena, A, B?hr, M, Kügler, S (2014) Pharmacologically controlled, discontinuous GDNF gene therapy restores motor function in a rat model of Parkinson’s disease. Neurobiol Dis 65: pp. 35-42 CrossRef
  5. Choi, SS, Lee, SR, Kim, SU, Lee, HJ (2014) Alzheimer’s disease and stem cell therapy. Exp Neurobiol 23: pp. 45-52 CrossRef
  6. Ginsberg, MD (2009) Current status of neuroprotection for cerebral ischemia: synoptic overview. Stroke 40: pp. S111-4 CrossRef
  7. Xian, YF, Lin, ZX, Mao, QQ, Ip, SP, Su, ZR, Lai, XP (2012) Protective effect of isorhynchophylline against β-amyloid-induced neurotoxicity in PC12 cells. Cell Mol Neurobiol 32: pp. 353-60 CrossRef
  8. Li, JW, Vederas, JC (2009) Drug discovery and natural products: end of era or an endless frontier?. Science 325: pp. 161-5 CrossRef
  9. Harvey, AL (2008) Natural products in drug discovery. Drug Discov Today 13: pp. 894-901 CrossRef
  10. Newman, DJ, Cragg, GM (2012) Natural products as sources of new drugs over the 30?years from 1981 to 2010. J Nat Prod 75: pp. 311-35 CrossRef
  11. Koehn, FE, Carter, GT (2005) The evolving role of natural products in drug discovery. Nat Rev Drug Discov 4: pp. 206-20 CrossRef
  12. Yu, X (2006) Present status and prospect using Ligusticum chuanxiong to prevent and treat stroke. Chin J Integr Med Cardio-/Cerebrovasc Dis 4: pp. 339-41
  13. Kim, H (2005) Neuroprotective herbs for stroke therapy in traditional eastern medicine. Neurol Res 27: pp. 287-301 CrossRef
  14. Kao, TK, Ou, YC, Kuo, JS, Chen, WY, Liao, SL, Wu, CW (2006) Neuroprotection by tetramethylpyrazine against ischemic brain injury in rats. Neurochem Int 48: pp. 166-76 CrossRef
  15. Zhang, C, Wang, SZ, Zuo, PP, Cui, X, Cai, J (2004) Protective effect of tetramethylpyrazine on learning and memory function in D-galactose-lesioned mice. Chin Med Sci J 19: pp. 180-4
  16. Lu, C, Zhang, J, Shi, X, Miao, S, Bi, L, Zhang, S (2014) Neuroprotective effects of tetramethylpyrazine against dopaminergic neuron injury in a rat model of Parkinson’s disease induced by MPTP. Int J Biol Sci 10: pp. 350-7 CrossRef
  17. Xu K, Wang PL, Xu X, Chu FH, Lin JX, Zhang YZ, et al. An overview on structural modifications of ligustrazine and biological evaluation of its synthetic derivatives. Res Chem Intermediat. 2013. doi:10.1007/s11164-13-281-.
  18. Cheng, XC, Liu, XY, Xu, WF, Guo, XL, Zhang, N, Song, YN (2009) Ligustrazine derivatives. Part 3: design, synthesis and evaluation of novel acylpiperazinyl derivatives as potential cerebrocardiac vascular agents. Bioorg Med Chem 17: pp. 3018-24 CrossRef
  
• 刊物类别：Chemistry and Materials Science
• 出版者：Chemistry Central Ltd
• ISSN：1752-153X

文摘

Background Ligustrazine has potent effects of thrombolysis, neuroprotection and vascular protection, which were important for effectively protecting the nervous system. Previous study in our laboratory reported that ligustrazine-benzoic acid derivatives have been shown to exhibit beneficial effect against CoCl2-induced neurotoxicity in differentiated PC12 cells. To further improve ligustrazine’s neuroprotection, we integrated the ligustrazine and phenolic acid fragments into one molecule via an amide bond based on structural combination. Results In this study, 12 novel ligustrazine-phenolic acid derivatives were synthesized and nine others were prepared by improved methods. Furthermore, these compounds were evaluated for their protective effects against CoCl2-induced neurotoxicity in differentiated PC12 cells. The amides conjunctional derivatives exhibited promising neuroprotective activities in comparison with ligustrazine. In addition, the most active congener (E)-3-(2,3,4-trimethoxyphenyl)-N-((3,5,6-trimethylpyrazin-2-yl)methyl)acrylamide (L10, EC50--5?μM), which is 2 times higher than that of ligustrazine, may be a potential candidate for intervention in neurological diseases. Structure-activity relationship was discussed briefly. Conclusions Results of series of ligustrazinyl amides enrich the study of ligustrazine derivatives with neuroprotective effects. Our completed work supports that the attempt to apply structure combination to discover more efficient neuroprotection lead compounds is viable. Graphical Abstract Ligustrazinyl Amides L1-L21 with Neuroprotective Effects.