DOI QR코드

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Synthesis and Biological Evaluation of Heterocyclic Ring-substituted Chalcone Derivatives as Novel Inhibitors of Protein Tyrosine Phosphatase 1B

  • Chen, Zhen-Hua (Key Laboratory of Natural Resources and Functional Molecules of the Changbai Mountain, Affiliated Ministry of Education, Yanbian University College of Pharmacy) ;
  • Sun, Liang-Peng (Key Laboratory of Natural Resources and Functional Molecules of the Changbai Mountain, Affiliated Ministry of Education, Yanbian University College of Pharmacy) ;
  • Zhang, Wei (National Center for Drug Screening, Shanghai Institute of Materia Medica, Shanghai Institute for Biological Science, Chinese Academy of Science) ;
  • Shen, Qiang (National Center for Drug Screening, Shanghai Institute of Materia Medica, Shanghai Institute for Biological Science, Chinese Academy of Science) ;
  • Gao, Li-Xin (National Center for Drug Screening, Shanghai Institute of Materia Medica, Shanghai Institute for Biological Science, Chinese Academy of Science) ;
  • Li, Jia (National Center for Drug Screening, Shanghai Institute of Materia Medica, Shanghai Institute for Biological Science, Chinese Academy of Science) ;
  • Piao, Hu-Ri (Key Laboratory of Natural Resources and Functional Molecules of the Changbai Mountain, Affiliated Ministry of Education, Yanbian University College of Pharmacy)
  • 투고 : 2011.04.20
  • 심사 : 2012.01.01
  • 발행 : 2012.05.20

초록

Protein tyrosine phosphatase 1B (PTP1B) is a key factor in negative regulation of the insulin pathway, and is a promising target for the treatment of type-II diabetes, obesity and cancer. Herein, compound ($\mathbf{4}$) was first observed to have moderate inhibitory activity against PTP1B with an $IC_{50}$ value of $13.72{\pm}1.53{\mu}M$. To obtain more potent PTP1B inhibitors, we synthesized a series of chalcone derivatives using compound ($\mathbf{4}$) as the lead compound. Compound $\mathbf{4l}$ ($IC_{50}=3.12{\pm}0.18{\mu}M$) was 4.4-fold more potent than the lead compound $\mathbf{4}$ ($IC_{50}=13.72{\pm}1.53{\mu}M$), and more potent than the positive control, ursolic acid ($IC_{50}=3.40{\pm}0.21{\mu}M$). These results may help to provide suitable drug-like lead compounds for the design of inhibitors of PTP1B as well as other PTPs.

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피인용 문헌

  1. Antidiabetic agents: past, present and future vol.5, pp.4, 2013, https://doi.org/10.4155/fmc.13.13