Design, Synthesis, and Biological Evaluation of Novel Bisurea Derivatives of p-Xylylenediamine as Potent Anti-Diabetic Agents

A series of novel bisurea derivatives of p-xylylenediamine were synthesized using triethylamine as a base catalyst in THF at reflux conditions from the reaction 1,1′-(1,4-phenylenebis(methylene)amine) with various isocyanates 2a–2e. The synthesized compounds were structurally characterized using spectral NMR (1H and 13C), FT-IR, LCMS, elemental analysis and screened in vitro biological assays and anti-hyperglycemic activities. The novel synthesized 3c compound showing good antioxidant with maximum zone of inhibition and showed the strongest inhibitory activity against α-amylase (IC50 = 27.69 µM) and α-glucosidase (IC50 = 27.67 µM). A 57.5% of fasting blood glucose (FBG) levels was reduced by 3c compound in diabetic rats; these in vitro results were subjected to QPLD. The 3c compound exhibits good correlation with strong interactions to α-amylase and α-glucosidase with –59.77 and –79.50 MMGBSA, respectively. The dynamics simulation has revealed more consistency by 3c.