Design, synthesis, docking and biological evaluation of chalcones as promising antidiabetic agents.

Diabetes mellitus (DM) is a serious chronic metabolic disorder which occurs due to dysfunction of insulin and therapeutic approaches are poor. It is an under estimation that 387 million people currently suffering globally with diabetic and more than 592 million people may be affected by 2030. It makes an urgent necessity to discover novel drugs to control amplified diabetic populations. In this study, amino chalcones (3a-j) were synthesized and hydroxy chalcones (3g-j) were isolated from natural source such as Sophora interrupta, Clerodendrum phlomidis and Andrographis macrobotrys. Structural elucidation was carried out using Mass, ¹H and ¹³C NMR Spectra. In vivo studies were carried out with alloxan induced diabetic rats (100 mg/kg) which reveals compounds 3c, 3a and 3h have significant antidiabetic efficacy with decreased blood glucose levels in the diabetic rats while compared with control rats. Besides, docking studies with aldose reductase, dipeptidyl peptidase, PPAR and glucosidase were monitored which accomplishes that the compounds 3c, 3i, 3a and 3d have eloquent binding affinity (kcal/mol) with aldose reductase, besides the chalcones 3c, 3b, 3d, 3e and 3i were also showed inhibition with DPP-IV, PPAR-α and α-glucosidase. Also, these compounds explicated distinct interactions i.e., π-π, π-cationic, polar, electrostatic and hydrophobic bonds were observed with key residues of binding pockets. Bioavailability is disclosed with Lipinski rule of five and the design pharmacokinetic as well as pharmacodynamic properties are reliable. Therefore, chalcones were implied as antidiabetic leads for in further studies and could be worthwhile for the development of new classes of effective antidiabetic agents.