1. Synthesis and evaluation of novel oleanolic acid derivatives as potential antidiabetic agents.
- Author
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Zhang L, Jia X, Dong J, Chen D, Liu J, Zhang L, and Wen X
- Subjects
- Binding Sites, Enzyme Activation drug effects, Glucose metabolism, Glycogen Phosphorylase antagonists & inhibitors, Glycogen Phosphorylase metabolism, Hep G2 Cells, Humans, Hydrogen Bonding, Hypoglycemic Agents chemistry, Hypoglycemic Agents pharmacology, Inhibitory Concentration 50, Molecular Docking Simulation, Oleanolic Acid chemical synthesis, Oleanolic Acid chemistry, Oleanolic Acid metabolism, Oleanolic Acid pharmacology, Protein Binding drug effects, Protein Structure, Tertiary, Triazoles chemistry, Triazoles metabolism, Triazoles pharmacology, Hypoglycemic Agents chemical synthesis, Oleanolic Acid analogs & derivatives, Triazoles chemical synthesis
- Abstract
Antidiabetic agents simultaneously inhibiting hepatic glucose production and stimulating hepatic glucose consumption could apply a better control over hyperglycemia. A series of oleanolic acid derivatives with bulky substituents at C-3 position were designed and synthesized in order to search for this kind of agents. All of the compounds were evaluated biologically in vitro using glycogen phosphorylase and HepG2 cells. The results indicated that several derivatives exhibited moderate-to-good inhibitory activities against glycogen phosphorylase. Compound 8g showed the best inhibition with an IC50 value of 5.4 μm. Moreover, most of the derivatives were found to increase the glucose consumption in HepG2 cells in a dose-dependent manner. The possible binding mode of compound 8g with glycogen phosphorylase was also explored by docking study. 8g was found to have hydrogen bonding interactions with Arg193, Arg310, and Arg60 of the allosteric site., (© 2013 John Wiley & Sons A/S.)
- Published
- 2014
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