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

Li G, Xu X, Xu K, Chu F, Song J, Zhou S, Xu B, Gong Y, Zhang H, Zhang Y, Wang P, Lei H - Chem Cent J (2015)

Bottom Line: Ligustrazine has potent effects of thrombolysis, neuroprotection and vascular protection, which were important for effectively protecting the nervous system.Results of series of ligustrazinyl amides enrich the study of ligustrazine derivatives with neuroprotective effects.Graphical AbstractLigustrazinyl Amides L1-L21 with Neuroprotective Effects.

View Article: PubMed Central - PubMed

Affiliation: School of Chinese Pharmacy, Beijing University of Chinese Medicine, No.6 Wangjing Middle Ring South Road, Beijing, Chaoyang District China.

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.

No MeSH data available.


Related in: MedlinePlus

Effects of L10 on differentiated PC12 cell injury in morphology (×200). (A) Control PC12 cells maintained under normal conditions. (B) PC12 cells exposed to NGF. (C) Differentiated PC12 cells exposed to CoCl2 insult. (D) Differentiated PC12 cells pre-incubated with L11 then exposed to CoCl2 insult.
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Fig1: Effects of L10 on differentiated PC12 cell injury in morphology (×200). (A) Control PC12 cells maintained under normal conditions. (B) PC12 cells exposed to NGF. (C) Differentiated PC12 cells exposed to CoCl2 insult. (D) Differentiated PC12 cells pre-incubated with L11 then exposed to CoCl2 insult.

Mentions: Observed under optical microscopy (OLMPUS, Japan), as shown in Figure 1-A, we found that undifferentiated PC12 cells that maintained under normal conditions were small and proliferated to form clone-like cell clusters without neural characteristics. By exposure to NGF, normal differentiated PC12 cells showed fine dendritic networks similar to those nerve cells (Figure 1-B). In contrast, CoCl2-insulted differentiated PC12 cells developed mild cell body swelling and some cells shrunk the dendritic networks even lost neurites demonstrating round shape (Figure 1-C). Pretreatment with L10 alleviated morphological manifestations of cells damage compared to model cells (Figure 1-D).Figure 1


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

Li G, Xu X, Xu K, Chu F, Song J, Zhou S, Xu B, Gong Y, Zhang H, Zhang Y, Wang P, Lei H - Chem Cent J (2015)

Effects of L10 on differentiated PC12 cell injury in morphology (×200). (A) Control PC12 cells maintained under normal conditions. (B) PC12 cells exposed to NGF. (C) Differentiated PC12 cells exposed to CoCl2 insult. (D) Differentiated PC12 cells pre-incubated with L11 then exposed to CoCl2 insult.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4372684&req=5

Fig1: Effects of L10 on differentiated PC12 cell injury in morphology (×200). (A) Control PC12 cells maintained under normal conditions. (B) PC12 cells exposed to NGF. (C) Differentiated PC12 cells exposed to CoCl2 insult. (D) Differentiated PC12 cells pre-incubated with L11 then exposed to CoCl2 insult.
Mentions: Observed under optical microscopy (OLMPUS, Japan), as shown in Figure 1-A, we found that undifferentiated PC12 cells that maintained under normal conditions were small and proliferated to form clone-like cell clusters without neural characteristics. By exposure to NGF, normal differentiated PC12 cells showed fine dendritic networks similar to those nerve cells (Figure 1-B). In contrast, CoCl2-insulted differentiated PC12 cells developed mild cell body swelling and some cells shrunk the dendritic networks even lost neurites demonstrating round shape (Figure 1-C). Pretreatment with L10 alleviated morphological manifestations of cells damage compared to model cells (Figure 1-D).Figure 1

Bottom Line: Ligustrazine has potent effects of thrombolysis, neuroprotection and vascular protection, which were important for effectively protecting the nervous system.Results of series of ligustrazinyl amides enrich the study of ligustrazine derivatives with neuroprotective effects.Graphical AbstractLigustrazinyl Amides L1-L21 with Neuroprotective Effects.

View Article: PubMed Central - PubMed

Affiliation: School of Chinese Pharmacy, Beijing University of Chinese Medicine, No.6 Wangjing Middle Ring South Road, Beijing, Chaoyang District China.

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.

No MeSH data available.


Related in: MedlinePlus