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A novel PTP1b inhibitor vanadium-flavone complex: synthesis and pharmacodynamic evaluation in streptozotocin-induced diabetic mice

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Abstract

Protein tyrosine phosphatase 1b is a negative regulator of insulin action and is emerging as a potential drug target for type 2 diabetes mellitus. A novel protein tyrosine phosphatase 1b inhibitor vanadium-flavone complex, bis(5,6,7-trihydroxyflavone)-oxovanadium, was synthesized and characterized by mass spectrometer, inductively coupled plasma, infrared, ultraviolet, electron paramagnetic resonance, X-ray photoelectron spectroscopy and thermal gravity analysis. Bis(5,6,7-trihydroxyflavone)-oxovanadium showed good anti-diabetic effect in streptozocin -induced diabetic mice without gastrointestinal stimulation and induction of hypoglycemia in normoglycemic mice. In vitro, the protein tyrosine phosphatase 1b inhibition activity of bis(5,6,7-trihydroxyflavone)-oxovanadium was enhanced after storage, during which bis(5,6,7-trihydroxyflavone)-oxovanadium could be decomposed gradually and the concentration of VO2+ would gradually increase. In vivo, baicalein not only transports VO2+ to the target organ, but also improves the morphology and function of pancreatic islets via its anti-inflammation activity. Thus bis(5,6,7-trihydroxyflavone)-oxovanadium is a promising potential drug for the treatment of type 2 diabetes mellitus.

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Acknowledgements

This work was supported by National Natural Science Foundation of China (U1607101), Natural Science Foundation of Liaoning Province (2015020199) and the Science and Technology Research Foundation of Education Department of Liaoning Province (201610163L11). We thank Mr. Abdul Rauf and Yan Xing for many helpful suggestions to this manuscript.

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Authors and Affiliations

  1. State key Laboratory of Fine Chemicals, Department of Materials Science and Chemical Engineering, School of Chemical Engineering, Dalian University of Technology, 2 Linggong Road, Dalian, 116024, Liaoning, People’s Republic of China

    Liying Duan, Junwei Ye, Wei-tao Gong & Guiling Ning

  2. Key Laboratory of Structure-Based Drug Design and Discovery (Shenyang Pharmaceutical University), Ministry of Education, Culture road NO. 103, Shenyang, 110016, Liaoning, People’s Republic of China

    Liying Duan & Shaoning Wang

  3. School of Life Science and Biotechnology, Dalian University of Technology, 2 Linggong Road, Dalian, 116024, Liaoning, People’s Republic of China

    Wenlong Sun & Yuesheng Dong

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  1. Liying Duan
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  2. Junwei Ye
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  3. Wenlong Sun
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  4. Shaoning Wang
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  5. Wei-tao Gong
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  6. Yuesheng Dong
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  7. Guiling Ning
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Correspondence to Yuesheng Dong or Guiling Ning.

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Duan, L., Ye, J., Sun, W. et al. A novel PTP1b inhibitor vanadium-flavone complex: synthesis and pharmacodynamic evaluation in streptozotocin-induced diabetic mice. Med Chem Res 26, 1863–1870 (2017). https://doi.org/10.1007/s00044-017-1895-9

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  • DOI: https://doi.org/10.1007/s00044-017-1895-9

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