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Synthesis and anti-inflammatory effects of a series of novel 9-O-substituted berberine derivatives

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Abstract

Berberine owns multiple pharmacological activities, especially anti-inflammatory activity. To enhance the anti-inflammatory therapeutic efficiency of berberine, a series of novel 9-O-substituted berberine derivatives (5a–5d) were synthesized and their anti-inflammatory activities were evaluated. 13C-NMR, 1H-NMR, IR and high resolution mass spectrum (HRMS) results indicated that these derivatives were successfully synthesized. The xylene-induced inflammatory mice model demonstrated that these derivatives showed dose-dependent inhibition of ear inflammatory swelling. Comparing to berberine, ibuprofen and naproxen-modified berberine derivatives enhanced anti-inflammatory activities, while aspirin and nicotinic acid-modified berberine derivatives showed lower anti-inflammatory effects at the same dosages. This could be attributed to the enhanced inhibition of secretion of cytokines, including interleukin-6 and tumor necrosis factor-α, by ibuprofen and naproxen berberine derivatives, while aspirin and nicotinic acid berberine derivatives showed lower inhibition of tumor necrosis factor-α than berberine. These results suggest that ibuprofen and naproxen-modified berberine derivatives are promising new anti-inflammatory drug candidates.

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Acknowledgements

This work was funded by National Natural Science Foundation of China (81301258), Hunan Provincial Natural Science Foundation of China (2016JJ2161), Specialized Research Fund for the Doctoral Program of Higher Education of China (20130162120078), China Postdoctoral Science Foundation (2013M540644), International Postdoctoral Exchange Fellowship Program (2014) 29 (20140014) and Shenghua Yuying Project of Central South University. The authors acknowledge the NMR measurements by The Modern Analysis and Testing Center of Central South University.

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Authors and Affiliations

  1. Department of Pharmaceutics, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410013, China

    Zhenbao Liu

  2. Department of Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, Central South University, Changsha, 410083, China

    Xiaohong Wang, Hang Zhang, Shanshan Zhang, Yiqian Li & Yanfei Liu

  3. Department of Medicinal Chemistry, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, 410208, China

    Dongming Peng

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  1. Zhenbao Liu
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  2. Xiaohong Wang
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Correspondence to Yanfei Liu or Dongming Peng.

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Liu, Z., Wang, X., Zhang, H. et al. Synthesis and anti-inflammatory effects of a series of novel 9-O-substituted berberine derivatives. Med Chem Res 26, 672–679 (2017). https://doi.org/10.1007/s00044-017-1787-z

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  • DOI: https://doi.org/10.1007/s00044-017-1787-z

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