1. Discovery and anti-diabetic effects of novel isoxazole based flavonoid derivatives.
- Author
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Nie, Jiang-Ping, Qu, Zhen-Ni, Chen, Ying, Chen, Jia-Hao, Jiang, Yue, Jin, Mei-Na, Yu, Yang, Niu, Wen-Yan, Duan, Hong-Quan, and Qin, Nan
- Subjects
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CELL lines , *CELLULAR signal transduction , *DRUG design , *ENZYMES , *HETEROCYCLIC compounds , *HYPOGLYCEMIC agents , *INSULIN resistance , *PHOSPHATASES , *PHOSPHORYLATION , *PROTEIN kinases - Abstract
3-O-[(E)-4-(4-cyanophenyl)-2-oxobut-3-en-1-yl] kaempferol is a novel lead compound to discover anti-diabetic and anti-obesity drugs. The present study reported the scaffold hopping of the lead compound to obtain a new isoxazole derivative, C45 , which has improved glucose consumption at the nanomolar level (EC 50 = 0.8 nM) in insulin resistant (IR) HepG2 cells. Western blotting showed that C45 markedly enhanced the phosphorylation of AMPK (AMP-activated protein kinase) and reduced the levels of the gluconeogenesis key enzymes PEPCK (phosphoenolpyruvate carboxykinase) and G6Pase (glucose 6-phosphatase) in HepG2 cells. The potential molecular mechanism of C45 may be activation of the AMPK/PEPCK/G6Pase pathways. We concluded that C45 might be a valuable candidate to discover anti-diabetic drugs. Unlabelled Image [ABSTRACT FROM AUTHOR]
- Published
- 2020
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