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

Chengqian Xiao; Yunan Tian; Min Lei; Fanglei Chen; Xianwen Gan; Xingang Yao; Xu Shen; Jing Chen; Lihong Hu

doi:10.1016/j.bmcl.2016.09.064

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. Epub 2016 Sep 28.

Authors

Chengqian Xiao¹, Yunan Tian², Min Lei³, Fanglei Chen¹, Xianwen Gan¹, Xingang Yao², Xu Shen², Jing Chen⁴, Lihong Hu⁵

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.

MeSH terms

Animals
Cell Line
Glucose*
Hypoglycemic Agents / chemical synthesis
Hypoglycemic Agents / pharmacology
Inhibitory Concentration 50
Insulin / metabolism*
Insulin Secretion
Insulin-Secreting Cells / drug effects*
Mice
Molecular Structure
Vinblastine / analogs & derivatives*
Vinblastine / chemical synthesis
Vinblastine / chemistry
Vinblastine / pharmacology

Substances

Hypoglycemic Agents
Insulin
vindoline
Vinblastine
Glucose