Exploring Aurone Derivatives as Potential Human Pancreatic Lipase Inhibitors through Molecular Docking and Molecular Dynamics Simulations.

Phuong Thuy Viet Nguyen,Cam-Van Thi Vo,Dat Van Truong,Han Ai Huynh,Thanh-Dao Tran

doi:10.3390/molecules25204657

Abstract

Inhibition of human pancreatic lipase, a crucial enzyme in dietary fat digestion and absorption, is a potent therapeutic approach for obesity treatment. In this study, human pancreatic lipase inhibitory activity of aurone derivatives was explored by molecular modeling approaches. The target protein was human pancreatic lipase (PDB ID: 1LPB). The 3D structures of 82 published bioactive aurone derivatives were docked successfully into the protein catalytic active site, using AutoDock Vina 1.5.7.rc1. Of them, 62 compounds interacted with the key residues of catalytic trial Ser152-Asp176-His263. The top hit compound (A14), with a docking score of −10.6 kcal⋅mol−1, was subsequently submitted to molecular dynamics simulations, using GROMACS 2018.01. Molecular dynamics simulation results showed that A14 formed a stable complex with 1LPB protein via hydrogen bonds with important residues in regulating enzyme activity (Ser152 and Phe77). Compound A14 showed high potency for further studies, such as the synthesis, in vitro and in vivo tests for pancreatic lipase inhibitory activity.

Highlights

IntroductionIndustrialization, urbanization, and modernization have shifted our lifestyle into an inactive one
Industrialization, urbanization, and modernization have shifted our lifestyle into an inactive one.Convenient processed food with a high degree of fat and free energy sugar exists more often in our daily diets
We describe the exploration of aurone to inhibit pancreatic lipase molecular modeling approaches

Summary

Introduction

Industrialization, urbanization, and modernization have shifted our lifestyle into an inactive one. Convenient processed food with a high degree of fat and free energy sugar exists more often in our daily diets. With these changes, the global obese and overweight population have almost tripled since 1975 [1]. A complicated and multifactorial disease, mostly arises from the imbalance between energy intake and energy consumption in the body. Obesity elevates the risk of other serious diseases, listing as diabetes [2,3], cardiovascular disorders [4,5], and certain cancers [6].

Methods

Discussion

Conclusion