Messagenin-based Chalcones: Synthesis, Modification and Perspectives of Antidiabetic Potency

A series of messagenin-based chalcones has been synthesized by Claisen-Schmidt condensation and screened for in vitro alpha-glucosidase inhibitory activity. The heterocyclization of 30-(3-pyridinylidene)-messagenin led to syn/anti N-acetyl-pyrazoles in a ratio of 2 : 1 that were isolated by HPLC. Messagenin chalcones act as alpha-glucosidase inhibitors with IC50 range from 0.055 to 80.70 mu M. The lead nanomolar level alpha-glucosidase inhibitor 30-(4-hydroxymethyl-benzylidene)-messagenin 10 was studied for antihyperglycemic activity on streptozotocin-induced diabetic animal models using in vivo mechanism-based assays. In a rat model of STZ-induced T1DM, compound 10 (20 mg/kg, orally) exhibited antihyperlipidemic activity, reducing AIP (p>0.05) and CRI (p<0.05) compared to control. Compound 10 improved diabetic nephropathy, locomotor activity in rats, and reduced diabetes-related mortality.