Exploring Thiazolidinedione-Naphthalene Analogues as Potential Antidiabetic Agents: Design, Synthesis, Molecular Docking and In-vitro Evaluation.

Abstract

Thiazolidinedione-naphthalene analogues were synthesized and evaluated for antidiabetic activity as Pancreatic α-Amylase (PAA) and intestinal α-glucosidase (IAG) inhibitors. The activity of the compounds (14a-g,17a-k) is compared with acarbose as the standard drug and all the compounds shows good to moderate antidiabetic activity. In-vitro PAA and IAG inhibition assay is performed for the all compounds, the compounds 17e shows superior PAA and IAG inhibitory activity with respective to standard (IC₅₀ = 12.455 ± 0.04 μM and 9.145 ± 0. 01 μM). The molecular interaction with PAA and IAG protein was also studied with the help of molecular docking studies using AutoDock software. while SwissADME and Osiris property explorer tools computed in-silico drug likeliness and toxicity properties. The in-silico results confirmed the 17e 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 14g and 17e has good antioxidant potential IC₅₀ = 8.04 ± 0.02 μM and 6.36 ± 0.03 μM respectively among all compounds. In conclusion, in-vitro, in-silico antidiabetic and antioxidant studies revealed 17e compound was found to be potential compound.