Synthesis and Evaluation of Antidiabetic Potential of Gliptin-based Hybrid Scaffolds

Dipeptidyl peptidase-4 (DPP4) inhibitors are promising therapeutic targets for the treatment of a catastrophic disease, especially diabetes mellitus (DM), which contributed to a massive rate of mortality. This research work succinctly covers the significance and vital role of gliptins in diabetes management and in the potential areas of further antidiabetic research, making it a strong drug candidate for antidiabetic drug development. We illustrated herein molecular docking, synthesis, and biological evaluation of selected potent synthesized molecules. Additionally, all the potent compounds were characterized by means of MASS and NMR spectral analysis, whereas the purity of these molecules were assessed by HPLC method. In order to determine the efficacy and cytotoxicity of synthesized gliptin-based scaffolds, in-vitro anti-oxidant and MTT assays with the implantation of DPPH and THP-1 cell lines, respectively, were performed. The results data disclose the anti-oxidant and biosafety potential of the newly schemed compounds. Based on in-vitro screening outcomes, only a derivative that exhibited potent efficacy was selected and subjected to an in-vivo study. Among them, compounds 6 and 12 are the most potent ones, which exhibited % radical scavenge of 89.38 % and 91.58 % related to standard ascorbic acid (91.58 %). Surprisingly, these compounds also exhibited excellent anti-diabetic efficacy at a dose of 4 mg/kg in an in-vivo animal model. In conclusion, all studies suggested that the titled molecules could be promising lead compounds for the treatment of patients with type 2 diabetes mellitus.