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

Compound <b>16f</b> displayed most potent inhibitory activity with IC₅₀ value of 4.58 μM. Kinetic studies revealed competitive mode of inhibition for <b>16f</b>, <b>16g</b>, and <b>16r</b> with <i>K_i</i> values 1.479, 1.827, and 1.939 μM; while their <i>V_max</i> 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 <b>16f</b> revealed stability of the protein-ligand complex. Moreover, compound <b>16f</b> was predicted to have a satisfactory drug likeness profile. Compound <b>16f</b> can be used as a leading candidate for further structural optimization to identify more potent and efficacious PL inhibitors as anti-obesity agents.