IN SILICO DOCKING OF EPICATECHIN, CORILAGIN AND QUERCETIN AS POTENTIAL PANCREATIC LIPASE INHIBITOR

Abstract

Background: Obesity is a complex disease, caused by an imbalance between energy intake and energy consumption in the human body thus leading to one of the prominent diseases that affect the world. The statistic of obesity continues to increase worldwide every year due to many factors. Therefore, the major concern of today’s public health is to find an effective and safe treatment as an anti-obesity drug. Pancreatic lipase (PL) plays an essential role in the digestion of dietary lipids. Therefore, the primary target of the drug is to inhibit the activation of the PL enzyme. Orlistat is the only anti-obesity drug issued by the Food and Drug Administration (FDA) which is potent and specific in action.  However, this drug had shown some adverse effects on the gastrointestinal tract. Thence, the alternative solution from the natural origin as orlistat substitutes are in demand. In this study, natural compounds namely quercetin, epicatechin, and corilagin were identified as the potential anti-pancreatic agents. Materials and Methods: Molecular docking was done to assess the binding affinity of the phytochemicals. Both blind docking and focus docking were conducted. Blind docking was performed with no assumption of the potential binding site. While focus docking, focusing on the region covering the catalytic triad comprises Ser152, His263 and Asp176 which are the key residues for lipid absorption. Results: The result shows that the epicatechin-1lpb complex has the best potential as a PL inhibitor since it recorded the lowest average free binding energy (-8.66 Kcal/mol) and formed hydrogen bonds at pockets of the active sites (Ser152, His263 and Asp176). Epicatechin also yielded the highest number of hydrophobic interactions and the lowest K_i value which further stabilized the ligand complexes and strengthened the binding affinity. Conclusion: Thus, this preliminary in-silico result proposed Epicatechin as the best candidate as a PL inhibitor agent.