Design, synthesis and biological evaluation of N‐substituted indole‐thiazolidinedione analogues as potential pancreatic lipase inhibitors

Pancreatic Lipase (PL) is a key enzyme responsible for the digestion of 50%–70% of dietary triglycerides, hence its inhibition is considered as a viable approach for the management of obesity. A series of indole‐TZD hybrid analogues were synthesized, characterized and evaluated for their PL inhibitory activity. Knoevenagel condensation of various substituted indole‐3‐carboxaldehyde with substituted thiazolidinediones resulted in the formation of titled analogues. Analogues 6d and 6e exerted potent PL inhibitory activity (IC50‐6.19 and 8.96 µM, respectively). Further, these analogues exerted a competitive mode of PL inhibition. Moreover, molecular modelling studies were in agreement with the in vitro results (Pearson's r = .8682, p