Indole-thiazolidinedione-triazole hybrids: synthesis, molecular docking, absorption, distribution, metabolism and excretion (ADME) profiling, and biological evaluation as α-amylase inhibitors

A novel series of hybrid indole-thiazolidinedione-triazole derivatives (6a-l) were synthesized and assessed for their in vitro inhibitory activity against porcine pancreatic alpha-amylase. The synthetic procedure consists of 3 steps. A crucial step in this process involves the generation of novel target molecules using a Cu(I)-catalyzed azide-alkyne cycloaddition reaction. The alpha-amylase inhibition IC50 value of the targeted compounds ranged from 0.51 +/- 0.02 to 7.99 +/- 0.28 mu M as compared with 0.68 +/- 0.02 mu M with acarbose as the standard drug. Using the Autodock technique, all the derivatives 6a-l were subjected to molecular docking investigations against porcine pancreatic alpha-amylase (PDB ID: 1OSE). Moreover, it was discovered that the docked compounds had excellent binding affinities that ranged from -10.1 to -10.8 kcal/mol as compared with the standard -7.9 kcal/mol. Additionally, a comprehensive analysis of the physicochemical and pharmacokinetic properties associated with absorption, distribution, metabolism and excretion (ADME) was conducted for all the synthesized compounds. Graphical Abstract