title: Ligustrazinyl amides: a novel class of ligustrazine-phenolic acid derivatives with neuroprotective effects.
abstract: 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 = 25 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 AbstractLigustrazinyl Amides L1-L21 with Neuroprotective Effects.
authors: School of Chinese Pharmacy, Beijing University of Chinese Medicine, No.6 Wangjing Middle Ring South Road, Beijing, Chaoyang District China.
authors: Guoliang
authors: G
authors: Li
authors: School of Chinese Pharmacy, Beijing University of Chinese Medicine, No.6 Wangjing Middle Ring South Road, Beijing, Chaoyang District China.
authors: Xin
authors: X
authors: Xu
authors: School of Chinese Pharmacy, Beijing University of Chinese Medicine, No.6 Wangjing Middle Ring South Road, Beijing, Chaoyang District China.
authors: Kuo
authors: K
authors: Xu
authors: School of Chinese Pharmacy, Beijing University of Chinese Medicine, No.6 Wangjing Middle Ring South Road, Beijing, Chaoyang District China.
authors: Fuhao
authors: F
authors: Chu
authors: School of Chinese Pharmacy, Beijing University of Chinese Medicine, No.6 Wangjing Middle Ring South Road, Beijing, Chaoyang District China.
authors: Jixiang
authors: J
authors: Song
authors: School of Chinese Pharmacy, Beijing University of Chinese Medicine, No.6 Wangjing Middle Ring South Road, Beijing, Chaoyang District China.
authors: Shen
authors: S
authors: Zhou
authors: School of Chinese Pharmacy, Beijing University of Chinese Medicine, No.6 Wangjing Middle Ring South Road, Beijing, Chaoyang District China.
authors: Bing
authors: B
authors: Xu
authors: School of Chinese Pharmacy, Beijing University of Chinese Medicine, No.6 Wangjing Middle Ring South Road, Beijing, Chaoyang District China.
authors: Yan
authors: Y
authors: Gong
authors: Department of Pathology, Beijing University of Chinese Medicine, No.11 North Third Ring Road, Beijing, Chaoyang District China.
authors: Huazheng
authors: H
authors: Zhang
authors: Department of Pathology, Beijing University of Chinese Medicine, No.11 North Third Ring Road, Beijing, Chaoyang District China.
authors: Yuzhong
authors: Y
authors: Zhang
authors: School of Chinese Pharmacy, Beijing University of Chinese Medicine, No.6 Wangjing Middle Ring South Road, Beijing, Chaoyang District China.
authors: Penglong
authors: P
authors: Wang
authors: School of Chinese Pharmacy, Beijing University of Chinese Medicine, No.6 Wangjing Middle Ring South Road, Beijing, Chaoyang District China.
authors: Haimin
authors: H
authors: Lei
keywords: Ligustrazine derivative; Neuroprotective effect; PC12 cell; Phenolic acid