Chalcone-based aryloxypropanolamine as a potential antidiabetic and antidyslipidaemic agent

Abstract

The hybrid congener 3 derived from hydroxychalcone and pharmacophore oxypropanolamine for adrenergic receptor, along with its enantiomers 9a and 9b were selected from a series of compounds for detailed studies of their antidiabetic profile in sucrose-challenged, low-dosed, streptozotocin-induced diabetic rats and in db/db mice, and antidyslipidaemic profile in high fat diet-induced dyslipidaemic hamsters. The test compounds exhibited significant and consistent antidiabetic and antidyslipidaemic activities in the above models. The pharmacodynamic studies of two metabolites, 10 and 11, were undertaken. Metabolite 10 having greater bioavailability in plasma was synthesized and found to exhibit significant antidiabetic activity. The parent compound together with its active metabolites exhibited significant oral bioavailability, thus establishing compound 3 as a potential lead molecule for further studies.