Quinoline Based thiazolidinediones: Design, Synthesis, In Silico, In Vitro, Antioxidant and Antidiabetic Evaluation

Abstract In the present research work a sequence of substituted quinoline based thiazolidinedione moieties ( 12a–h) were designed and synthesized as potential antidiabetic agents. Pancreatic α‐amylase (PAA) and intestinal α‐glucosidase (IAG) enzymes were considered as potential targets for effective treatment of diabetes. The potential of all compounds (12a–h) was assessed in vitro against PAA and IAG using acarbose as standard. The results suggested that compound 12h has shown superior PAA and IAG inhibitory activity with respective to standard (IC 50  =  4.683 ± 0.06   µM and 2.456 ± 0.07 µM ). Furthermore, using computational (in silico) studies like AutoDock and Desmond, predicted the significant binding interactions responsible for the activity of all compounds (12a–h) at the active site of enzymes, while SwissADME and Osiris property explorer tools computed in silico drug likeliness and toxicity properties. The RMSD, RMSF, Rg and protein ligand contacts, confirmed the stable binding of compound 12h and 12g with the both PAA and IAG proteins. The in silico results confirmed the 12h molecule as a superior drug with high binding affinity and good drug likeness against PAA and IAG, confirming in vitro results. We also studied antioxidant activity (AOA) of all synthesized compounds and results confined that the compound 12h has good antioxidant potential ( IC 50  = 5.04 ± 0.054   µM) among all other compounds. In conclusion, in vitro, in silico and antioxidant studies revealed 12h compound was found to be potential compound.