Journal Article

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

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

2020

Overview

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.

• Publisher: MDPI AG,MDPI
• Subject: Amino acids / aurone / Benzofurans - chemistry / Benzofurans - pharmacology / Catalytic Domain / Enzyme Inhibitors - chemistry / Enzyme Inhibitors - pharmacology / Enzymes / Flavonoids / human pancreatic lipase / human pancreatic lipase inhibitors / Humans / Hydrogen Bonding / Hydrogen bonds / Ligands / Lipase - antagonists & inhibitors / Lipase - chemistry / Lipase - metabolism / molecular docking / Molecular Docking Simulation / Molecular Dynamics Simulation / molecular dynamics simulations / Obesity / Oils & fats / Orlistat - chemistry / Simulation