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Flavonoids as human carboxylesterase 2 inhibitors: Inhibition potentials and molecular docking simulations.
- Source :
-
International journal of biological macromolecules [Int J Biol Macromol] 2019 Jun 15; Vol. 131, pp. 201-208. Date of Electronic Publication: 2019 Mar 11. - Publication Year :
- 2019
-
Abstract
- In our search for natural human carboxylesterase 2 (hCE 2) inhibitors from natural products, we investigated inhibitory effects and mechanisms of flavonoids (1-16) against hCE 2. The results demonstrated that kurarinone (1), baicalein (2), 2-[(2'-(1-hydroxy-1-methylethyl)-7'-(3-methyl-2-butenyl)-2',3'-dihydrobenzofuran)-5-yl]-7-hydroxy-8-(3-methyl-2-butenyl)chroman-4-one (5), luteolin (6), kushenol X (9), and kushenol C (11) displayed significantly inhibitory effects against hCE 2 with IC <subscript>50</subscript> values of 1.46 ± 0.43, 5.22 ± 0.89, 1.13 ± 0.19, 9.78 ± 0.98, 3.05 ± 0.46, and 2.61 ± 0.52 μM, respectively. Compounds 1, 5, 6, 9, and 11 were all uncompetitive inhibitors with Ki values of 1.73, 1.59, 16.89, 1.72, and 0.79 μM, respectively, and their Km values ranged from 2.08 μM to 5.41 μM. Furthermore, molecular docking was conducted for investigating mechanisms of compounds 1, 5, 6, 9, and 11 with hCE 2. These results suggested that compounds 1, 5, 6, 9, and 11 could be served as lead compounds for the development of novel hCE 2 inhibitors.<br /> (Copyright © 2019. Published by Elsevier B.V.)
- Subjects :
- Enzyme Activation drug effects
Humans
Hydrolysis
Kinetics
Molecular Docking Simulation
Molecular Dynamics Simulation
Molecular Structure
Structure-Activity Relationship
Carboxylesterase antagonists & inhibitors
Carboxylesterase chemistry
Enzyme Inhibitors chemistry
Enzyme Inhibitors pharmacology
Flavonoids chemistry
Flavonoids pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0003
- Volume :
- 131
- Database :
- MEDLINE
- Journal :
- International journal of biological macromolecules
- Publication Type :
- Academic Journal
- Accession number :
- 30872054
- Full Text :
- https://doi.org/10.1016/j.ijbiomac.2019.03.060