Design, synthesis, characterization and in vivo studies of some hydroxylated chalcone derivatives as hypoglycemic agents

Abstract

Introduction: Low molecular weight ligands (LMWL) have a citadel reputation in the modulation of numerous therapeutic targets as a result of their smart uniqueness. The hydroxylated chalcone derivatives have been reported to be therapeutic agents owing to their capability to demonstrate multifarious pharmacological activities, however, their potential in lowering blood glucose levels is not yet explored fully. Methods: Corresponding aldehydes and acetophenones were made to react in an alcoholic basic medium to produce the desired chalcone scaffolds. The anti-hyperglycemic potentials of the derivatives were studied using the streptozotocin-induced diabetic rat model. Compounds 3d, 3f, 3g, 3h, and 3j demonstrated excellent anti-hyperglycemic activity. Results: Chalcone 3d, having an ortho-methoxy substituent in B-ring, displayed the highest hypoglycemic potential with a 26.9% lowering of blood glucose level compared to standard acarbose which exhibited a 34.7% reduction. Compounds 3a, 3c, and 3e showed the lowest activity. Discussion: The study revealed the potential of chalcone scaffolds in lessening the blood glucose level by 7.1% to 26.9%. The ortho-position was observed to be high opportunistic for inducing the hypoglycemia activity as compared to para-position and para-position is, in turn, advantageous to the meta-position. Conclusions: The role of various substituents in modulating this enzyme function was studied. The electron-donating groups were found to be effectual for modulation of the anti-diabetic target compared to electron-withdrawing groups.