Design, synthesis, and biological evaluation of disubstituted thiazolidinedione derivatives as pancreatic lipase inhibitors for the management of obesity

Compound 16f displayed most potent inhibitory activity with IC₅₀ value of 4.58 μM. Kinetic studies revealed competitive mode of inhibition for 16f, 16g, and 16r with Ki values 1.479, 1.827, and 1.939 μM; while their Vmax values were found to be 0.611, 0.958, and 0.939 μM, respectively. Docking studies confirmed good binding affinities of synthesized derivatives toward the active site of PL. Molecular dynamic simulation of 16f revealed stability of the protein-ligand complex. Moreover, compound 16f was predicted to have a satisfactory drug likeness profile. Compound 16f can be used as a leading candidate for further structural optimization to identify more potent and efficacious PL inhibitors as anti-obesity agents.