Identification of Novel Thiazolidinedione Based Pancreatic Lipase Inhibitors for the Management of Obesity Using In Silico Approach

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Abstract Accumulation of excessive fat in the body is an indication of obesity, which is becoming an alarming health concern around the world. Pancreatic lipase has been found to have a promising role in the digestion of dietary fats thereby inhibition of pancreatic lipase can be a therapeutic strategy for the management of obesity. Literature showed the anti‐pancreatic lipase potential of thiazolidinediones thereby the current study is designed to identify substituted thiazolidinedione‐based molecules as pancreatic lipase inhibitors. A 3D QSAR model with R 2 value of 0.7283 and Stability of 0.843 was generated to determine the nature of substitution necessary for the inhibitory activity. Based on the generated 3D QSAR, the activity of 352 novel‐designed molecules was predicted and further screened through pharmacokinetic parameters. These compounds were docked into the binding site of the pancreatic lipase which led to the identification of 14 hit molecules with dock score between −9.523 to −7.604 kcal/mol. The molecular simulation studies and free energy calculation of the hit compounds i. e. 87 and 80 revealed good stability and binding in the active site of pancreatic lipase. The current study provides 14 hit molecules, which can be synthesized and further evaluated to explore their anti‐pancreatic lipase inhibitory activity.

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