Natural soluble epoxide hydrolase inhibitors from Alisma orientale and their potential mechanism with soluble epoxide hydrolase.

Authors :: Zhao WY
Zhang XY
Zhou MR
Tian XG
Lv X
Zhang HL
Deng S
Zhang BJ
Sun CP
Ma XC
Source :: International journal of biological macromolecules [Int J Biol Macromol] 2021 Jul 31; Vol. 183, pp. 811-817. Date of Electronic Publication: 2021 May 03.
Publication Year :: 2021
Abstract: Inhibition of soluble epoxide hydrolase (sEH) is considered to be an effective treatment for inflammation-related diseases, and small molecules origin from natural products show promising activity against sEH. Two undescribed protostanes, 3β-hydroxy-25-anhydro-alisol F (1) and 3β-hydroxy-alisol G (2) were isolated from Alisma orientale and identified as new sEH inhibitors with IC <subscript>50</subscript> values of 10.06 and 30.45 μM, respectively. Potential lead compound 1 was determined as an uncompetitive inhibitor against sEH, which had a K <subscript>i</subscript> value of 5.13 μM. In-depth molecular docking and molecular dynamics simulations revealed that amino acid residue Ser374 plays an important role in the inhibition of 1, which also provides an idea for the development of sEH inhibitors based on protostane-type triterpenoids.<br /> (Copyright © 2021 Elsevier B.V. All rights reserved.)

Subjects :: Enzyme Inhibitors chemistry
Epoxide Hydrolases chemistry
Inhibitory Concentration 50
Models, Molecular
Molecular Docking Simulation
Molecular Dynamics Simulation
Molecular Structure
Pharmacokinetics
Plant Extracts chemistry
Plant Extracts pharmacology
Protein Conformation
Triterpenes chemistry
Alisma chemistry
Enzyme Inhibitors pharmacology
Epoxide Hydrolases antagonists & inhibitors
Triterpenes pharmacology

Full Text Access

Tools