Diabetes mellitus is a chronic metabolic disorder that is characterized by defects in endogenous insulin secretion or action. Metformin is the first-line drug of choice for the treatment of type 2 diabetes (T2D). It exerts antidiabetic effects by reducing hepatic glucose production and increased peripheral glucose utilization through activation of AMP-activated protein kinase (AMPK). Naringenin, a flavonoid exerts antidiabetic effects by inhibition of gluconeogenesis through upregulation of AMPK, hence metformin-like effects.
To identify AMPK as a potential target of synthetic chalco-naringenin analogs and putative therapeutic applications.
Chalco-naringenin analogs, were synthesized, characterized by IR, 1H-NMR and 13C-NMR. C2C12 and Chang cells were cultured in dulbecco's modified eagle medium (DMEM). MTT assay was used to determine cell viability and subjection to phospho-AMPKα (Thr172) sandwich ELISA Kit to determine phosphorylation of AMPK.
Chalcones were successfully synthesized and characterized through 13C-NMR and 1H-NMR spectroscopy. Docking scores of the chalcones suggested a good binding affinity of these compounds to AMPK. Cell viability as determined by MTT assays were found to be dose-dependent for all compounds, however 5k exerted reduced cell viability as compared to 5b. The effects of chalcones on AMPK phosphorylation were potentiated by co-treatment with metformin or naringenin.
The chalcones showed potential in expression of AMPK through computational chemistry, however in the in vitro model the effects of chalcones on AMPK were potentiated by metformin and naringenin. The chalcones could further be explored for their potential on AMPK activity in in vivo studies to develop therapeutic targets for the effective management of diabetes.