Synthesis and glucose-stimulate insulin secretion (GSIS) evaluation of vindoline derivatives.
It is demonstrated that natural product vindoline can enhance the glucose-stimulated insulin secretion (GSIS) in MIN6 cells with the EC50value 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.
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, PR China.
Chengqian
C
Xiao
CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, PR China.
Yunan
Y
Tian
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: mlei@simm.ac.cn.
Min
M
Lei
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, PR China.
Fanglei
F
Chen
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, PR China.
Xianwen
X
Gan
CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, PR China.
Xingang
X
Yao
CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, PR China.
Xu
X
Shen
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: jingchen@simm.ac.cn.
Jing
J
Chen
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: lhhu@simm.ac.cn.
Lihong
L
Hu
D000818:Animals; D002460:Cell Line; D005947:Glucose; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects*; D051379:Mice; D015394:Molecular Structure; D014747:Vinblastine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
D007004:Hypoglycemic Agents; D007328:Insulin; C009667:vindoline; D014747:Vinblastine; D005947:Glucose
Glucose-stimulate insulin secretion (GSIS); Natural product; Structure–activity relationships (SARs); Vindoline