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Medicinal Chemistry Research

, Volume 27, Issue 5, pp 1366–1373 | Cite as

Design, synthesis and neuroprotective activities of novel cinnamide derivatives containing benzylpiperazine moiety

  • Yan Zhong
  • Xiaofeng Li
  • Aixia Zhang
  • Yi Xu
  • Ping Li
  • Bin Wu
Original Research
  • 217 Downloads

Abstract

A new series of cinnamide derivatives 6al were synthesized by the reaction of acyl chlorides with various substituted benzylpiperazines. The structures were characterized by 1H NMR, 13C NMR, and HRMS. The potential neuroprotective activities of cinnamide analogs were evaluated in differentiated rat pheochromocytoma cells (PC12 cells) and in mice subjected to acute cerebral ischemia. Among the series, 6a, 6b, and 6c, featuring a 1,3-benzodioxole moiety, showed potent neuroprotection both in vivo and in vitro. The three compounds were selected and further studied to determine their mechanism of action. MTT assay, Hoechst 33342/PI double staining, and high content screening (HCS) revealed that pretreatment of the cells with 6a, 6b, and 6c has significantly decreased the extent of cell apoptosis in a dose-dependent manner. The results of western blot analysis demonstrated these compounds suppressed apoptosis of glutamate-induced PC12 cells via caspase-3 pathway. These compounds can be lead compounds for further discovery of neuroprotective agents for treating cerebral ischemic stroke.

Keywords

Cinnamide Neuroprotection Caspase-3 Cerebral ischemia Apoptosis 

Notes

Acknowledgements

The authors are grateful to the support from the National Natural Science Foundation of China (No. 81371451) and the Natural Science Foundation of Jiangsu Province (No. BK20131390).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.School of Chemistry and Chemical EngineeringSoutheast UniversityNanjingChina
  2. 2.School of PharmacyNanjing Medical UniversityNanjingChina
  3. 3.School of Basic Medical SciencesNanjing Medical UniversityNanjingChina

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