1. Discovery and anti-diabetic effects of novel isoxazole based flavonoid derivatives.
- Author
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Nie JP, Qu ZN, Chen Y, Chen JH, Jiang Y, Jin MN, Yu Y, Niu WY, Duan HQ, and Qin N
- Subjects
- Flavonoids chemistry, Glucose metabolism, Hep G2 Cells, Hepatocytes drug effects, Hepatocytes metabolism, Humans, Hypoglycemic Agents chemistry, Molecular Structure, Flavonoids pharmacology, Hypoglycemic Agents pharmacology
- 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., Competing Interests: Declaration of Competing Interest There are no conflicts to declare., (Copyright © 2020 Elsevier B.V. All rights reserved.)- Published
- 2020
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