Synthesis and glucose-stimulate insulin secretion (GSIS) evaluation of vindoline derivatives

  • Bioorg Med Chem Lett. 2017 Mar 1;27(5):1316-1318. doi: 10.1016/j.bmcl.2016.09.064.
Chengqian Xiao  1 ,  Yunan Tian  2 ,  Min Lei  3 ,  Fanglei Chen  1 ,  Xianwen Gan  1 ,  Xingang Yao  2 ,  Xu Shen  2 ,  Jing Chen  4 ,  Lihong Hu  5
Affiliations
  • 1. State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, PR China.
  • 2. CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, PR China.
  • 3. State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, PR China. Electronic address: [email protected].
  • 4. CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, PR China. Electronic address: [email protected].
  • 5. State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, PR China. Electronic address: [email protected].
PMID: 28162858 DOI: 10.1016/j.bmcl.2016.09.064
Abstract

It is demonstrated that natural product vindoline can enhance the glucose-stimulated Insulin secretion (GSIS) in MIN6 cells with the EC50 value of 50.2μM. In order to improve the activities, a series of vindoline derivatives are synthesized and evaluated in MIN6 cells. Compounds 4, 8, 17 and 24 show about 4.5 times more effective stimulation Insulin secretion ability (EC50: 10.4, 14.2, 11.0 and 12.7μM, respectively) than vindoline.

Keywords
Glucose-stimulate insulin secretion (GSIS); Natural product; Structure–activity relationships (SARs); Vindoline.