Molecular Docking and Pharmacokinetics Prediction of Piperine and Capsaicin as Human Pancreatic Lipase Inhibitors: An In Silico Study.

Introduction Obesity is a complex multifaceted disease, characterized by excessive body fat accumulation. It is a major public health concern globally, affecting individuals of all ages, genders, and socioeconomic backgrounds. Lipase, a key enzyme involved in lipid metabolism, plays a crucial role in the hydrolysis of dietary fats. Pancreatic lipase performs hydrolysis of nearly 50%-70% of total dietary fats. Thus, inhibition of pancreatic lipase is recognized as one of the strategies for managing obesity. Aim To predict the effect of phytocompounds from pepper as pancreatic lipase inhibitors using computational approaches. Methodology The drug-likeness and pharmacokinetic properties of compounds were evaluated using Lipinski rule of five and absorption, distribution, metabolism, and excretion (ADME) analysis, respectively. The drug score value was computed using Molinspiration, while the lipase inhibitor potential of ligands was evaluated using prediction of activity spectra for substances. Molecular docking was carried out to evaluate the stability and ligand binding affinity. Results Computational approaches identified both piperine and capsaicin as potential candidates, exhibiting favorable affinities with binding energy values of -9.9 and -7.7 kcal/mol, respectively. Both piperine and capsaicin interacted with Ser-152 and His-263, demonstrating their binding at the substrate binding site. Conclusions Findings provide insights into the underlying anti-obesity potential of these bioactive compounds from pepper and support further experimental investigations for obesity treatment.