scholarly journals Inhibitory Activity of Flavonoids, Chrysoeriol and Luteolin-7-O-Glucopyranoside, on Soluble Epoxide Hydrolase from Capsicum chinense

Biomolecules ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 180
Author(s):  
Jang Hoon Kim ◽  
Chang Hyun Jin
Keyword(s):  
Active Site ◽  
Epoxide Hydrolase ◽  
Soluble Epoxide Hydrolase ◽  
Capsicum Chinense ◽  
Allosteric Site ◽  
Left Edge ◽  
Enzyme Active Site ◽  
Tube Shape ◽  
Ic50 Values ◽  
Potential Inhibitors

Three flavonoids derived from the leaves of Capsicum chinense Jacq. were identified as chrysoeriol (1), luteolin-7-O-glucopyranoside (2), and isorhamnetin-7-O-glucopyranoside (3). They had IC50 values of 11.6±2.9, 14.4±1.5, and 42.7±3.5 µg/mL against soluble epoxide hydrolase (sEH), respectively. The three inhibitors (1–3) were found to non-competitively bind into the allosteric site of the enzyme with Ki values of 10.5 ± 3.2, 11.9 ± 2.8 and 38.0 ± 4.1 µg/mL, respectively. The potential inhibitors 1 and 2 were located at the left edge ofa U-tube shape that contained the enzyme active site. Additionally, we observed changes in several factors involved in the binding of these complexes under 300 K and 1 bar. Finally, it was confirmed that each inhibitor, 1 and 2, could be complexed with sEH by the “induced fit” and “lock-and-key” models.

scholarly journals Inhibitory Activity of Quercetin 3-O-Arabinofuranoside and 2-Oxopomolic Acid Derived from Malus domestica on Soluble Epoxide Hydrolase

Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4352
Author(s):  
In Sook Cho ◽  
Jang Hoon Kim ◽  
Yunjia Lin ◽  
Xiang Dong Su ◽  
Jong Seong Kang ◽  
...  
Keyword(s):  
Malus Domestica ◽  
Epoxide Hydrolase ◽  
Soluble Epoxide Hydrolase ◽  
Corosolic Acid ◽  
Allosteric Sites ◽  
Ic50 Values ◽  
Cardiovascular Tests ◽  
Potential Inhibitors ◽  
Molecular Docking And Dynamics

Flavonoids and triterpenoids were revealed to be the potential inhibitors on soluble epoxide hydrolase (sEH). The aim of this study is to reveal sEH inhibitors from Fuji apples. A flavonoid and three triterpenoids derived from the fruit of Malus domestica were identified as quercetin-3-O-arabinoside (1), ursolic acid (2), corosolic acid (3), and 2-oxopomolic acid (4). They had half-maximal inhibitory concentration of the inhibitors (IC50) values of 39.3 ± 3.4, 84.5 ± 9.5, 51.3 ± 4.9, and 11.4 ± 2.7 μM, respectively, on sEH. The inhibitors bound to allosteric sites of enzymes in mixed (1) and noncompetitive modes (2–4). Molecular simulations were carried out for inhibitors 1 and 4 to calculate the binding force of ligands to receptors. The inhibitors bound to the left (1) and right (4) pockets next to the enzyme’s active site. Based on analyses of their molecular docking and dynamics, it was shown that inhibitors 1 and 4 can stably bind sEH at 1 bar and 300 K. Finally, inhibitors 1 and 4 are promising candidates for further studies using cell-based assays and in vivo cardiovascular tests.

Stereoselectivity in the epoxide hydrolase catalyzed hydrolysis of the stereoisomeric 3-tert-butyl-1,2-epoxycyclohexanes. Further evidence for the topology of the enzyme active site

1982 ◽  
Vol 47 (16) ◽  
pp. 3105-3112 ◽  
Author(s):  
Giuseppe Bellucci ◽  
Giancarlo Berti ◽  
Roberto Bianchini ◽  
Pasquale Cetera ◽  
Ettore Mastrorilli
Keyword(s):  
Active Site ◽  
Epoxide Hydrolase ◽  
Enzyme Active Site ◽  
Tert Butyl ◽  
Hydrolysis Of

Insights into the Reaction Mechanism of Soluble Epoxide Hydrolase from Theoretical Active Site Mutants

2006 ◽  
Vol 110 (42) ◽  
pp. 21299-21310 ◽  
Author(s):  
Kathrin H. Hopmann ◽  
Fahmi Himo
Keyword(s):  
Reaction Mechanism ◽  
Active Site ◽  
Epoxide Hydrolase ◽  
Soluble Epoxide Hydrolase ◽  
Active Site Mutants

scholarly journals Coumarin and Moracin Derivatives from Mulberry Leaves (Morus alba L.) with Soluble Epoxide Hydrolase Inhibitory Activity

Molecules ◽  
2020 ◽  
Vol 25 (17) ◽  
pp. 3967
Author(s):  
Hong Xu Li ◽  
Myungsook Heo ◽  
Younghoon Go ◽  
Young Soo Kim ◽  
Young Ho Kim ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Epoxide Hydrolase ◽  
2D Nmr ◽  
Soluble Epoxide Hydrolase ◽  
Inhibitory Effect ◽  
Mulberry Leaves ◽  
Ic50 Values ◽  
Nmr Methods ◽  
Reported Data ◽  
Mixed Types

This study identified three coumarins (1–3), and six moracin derivatives (4–9). The structures of these natural compounds were determined by the spectroscopic methods, including 1D and 2D NMR methods, and comparison with previous reported data. All of the isolated compounds were assessed for the effects on the soluble epoxide hydrolase (sEH) inhibitory activity. Among them, compounds 1–7 exhibited significant inhibitory effect with 100% inhibitory, with IC50 values of 6.9, 0.2, 15.9, 1.1, 1.2, 9.9, and 7.7 µM, respectively. A kinetic study revealed that compounds 1–4, and 6 were competitive types of inhibitors, compounds 5 and 7 were mixed types of inhibitors. These results suggest that moracin and coumarin derivatives from mulberry leaves are significant sEH inhibitors.

scholarly journals Probing the orientation of inhibitor and epoxy-eicosatrienoic acid binding in the active site of soluble epoxide hydrolase

2017 ◽  
Vol 613 ◽  
pp. 1-11 ◽  
Author(s):  
Kin Sing Stephen Lee ◽  
Niel M. Henriksen ◽  
Connie J. Ng ◽  
Jun Yang ◽  
Weitao Jia ◽  
...  
Keyword(s):  
Active Site ◽  
Epoxide Hydrolase ◽  
Soluble Epoxide Hydrolase ◽  
Eicosatrienoic Acid

scholarly journals In Vitro and In Silico Studies of Soluble Epoxide Hydrolase Inhibitors from the Roots of Lycopus lucidus

Plants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 356
Author(s):  
Yoo Kyong Han ◽  
Ji Sun Lee ◽  
Seo Young Yang ◽  
Ki Yong Lee ◽  
Young Ho Kim
Keyword(s):  
Inhibitory Activity ◽  
Epoxide Hydrolase ◽  
Soluble Epoxide Hydrolase ◽  
In Silico Studies ◽  
Allosteric Sites ◽  
Soluble Epoxide Hydrolase Inhibitors ◽  
Ic50 Values ◽  
Dimethyl Lithospermate ◽  
Lycopus Lucidus

Soluble epoxide hydrolase (sEH) is an enzyme that is considered a potential therapeutic target in human cardiovascular disease. Triterpenes (1–4) and phenylpropanoids (5–10) were isolated from Lycopus lucidus to obtain sEH inhibitors through various chromatographic purificationtechniques. The isolated compounds were evaluated for their inhibitory activity against sEH, and methyl rosmarinate (7), martynoside (8), dimethyl lithospermate (9) and 9″ methyl lithospermate (10) showed remarkable inhibitory activity, with the IC50 values ranging from 10.6 ± 3.2 to 35.7 ± 2.1 µM. Kinetic analysis of these compounds revealed that 7, 9 and 10 were competitive inhibitors bound to the active site, and 8 was the preferred mixed type inhibitor for allosteric sites. Additionally, molecular modeling has identified interacting catalytic residues and bindings between sEH and inhibitors. The results suggest that these compounds are potential candidates that can be used for further development in the prevention and treatment for cardiovascular risk.

Sign in / Sign up

Export Citation Format

Share Document