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.
In this study, 82 aurone compounds, a subclass of flavonoids were investigated towards to human pancreatic lipase inhibitory activity. Molecular docking of the aurones was done successfully into the catalytic position of lipase (Pdb: 1LPB) using AutoDock Vina software 1.5.7.rc1. The results showed that 62 compounds interacted well with residues in the catalytic trial Ser152-Asp176-His263 and Phe77 of protein 1LPB. In particular, A32 was selected as the best binding compound (docking score: -10.6 kcal.mol -1 ) and suitable for oral drug following the 5-Lipinski rule. Combining the results of docking and molecular dynamics simulation of A32-protein complex during 10 ns, this study performed that the A32 compound bound well and formed a stable complex with 1LPB protein. Therefore, the A32 compound was considered as the lead compound which could be synthesized and tested for pancreatic lipase inhibitor.Obesity is considered as a complex disease, with a variety of factors and causes, in which the most commonly is an unreasonable diet and unhealthy lifestyle leading to an imbalance between energy supplement and energy consumption in the body [1]. It opens up the way for for the obesity drug research, which is the inhibition of fat hydrolysis of human pancreatic lipase (HPL). Cause, HPL along with co-factors Colipase and Ca2+, play a main role in the process digestion and absorption of fat. HPL hydrolyzes 50 -70% of the total fat from the food, so inhibiting HPL will significantly reduce the amount of absorbed fat [2,3].Nowadays, many in silico models are being applied to finding potential bioactive compounds for the treatment of obesity [2,4,[5][6][7]. These models made the new drug research more clearly oriented and helped to save both cost and time. Besides that, there is a need to develop new drugs having fewer side effects and more safety, specifically taking from natural compounds for HPL inhibitory activities. The results have discovered natural compounds belonging to many different groups of structures such as saponins, alkaloids, carotenoids, flavonoids that inhibited HPL enzyme [2,4]. In particular, flavonoids with subclasses such as flavone, flavonole, chalcone have been extensively studied and the researches obtained many good HPL inhibition results with the IC50 values determined as Licochalcone A (IC50 35 µg/ml) [5], Galangin (IC50 48.20 mg/ml) [6], Hesperidin (IC50
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.