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.

scholarly journals IN VITRO SOLUBLE EPOXIDE HYDROLASE ENZYME INHIBITORY ACTIVITY OF SOME NOVEL CHALCONE DERIVATIVES

2012 ◽  
Vol 2 (4) ◽  
Author(s):  
Kuppusamy Asokkumar ◽  
Lokeswari Prathyusha Tangella ◽  
Muthusamy Umamaheshwari ◽  
Thirumalaisamy Shivashanmugam ◽  
Varadharajan Subhadradevi ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Epoxide Hydrolase ◽  
Soluble Epoxide Hydrolase ◽  
Chalcone Derivatives

In vitro and in silico investigation of anthocyanin derivatives as soluble epoxide hydrolase inhibitors

2018 ◽  
Vol 112 ◽  
pp. 961-967 ◽  
Author(s):  
Jang Hoon Kim ◽  
In Sook Cho ◽  
Jaihyuk Ryu ◽  
Ji Sun Lee ◽  
Jong Seong Kang ◽  
...  
Keyword(s):  
In Silico ◽  
Epoxide Hydrolase ◽  
Soluble Epoxide Hydrolase ◽  
Soluble Epoxide Hydrolase Inhibitors

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.

scholarly journals In vitro and in vivo metabolism of N-adamantyl substituted urea-based soluble epoxide hydrolase inhibitors

2015 ◽  
Vol 98 (4) ◽  
pp. 718-731 ◽  
Author(s):  
Jun-Yan Liu ◽  
Hsing-Ju Tsai ◽  
Christophe Morisseau ◽  
Jozsef Lango ◽  
Sung Hee Hwang ◽  
...  
Keyword(s):  
Epoxide Hydrolase ◽  
Soluble Epoxide Hydrolase ◽  
In Vivo Metabolism ◽  
Soluble Epoxide Hydrolase Inhibitors ◽  
Substituted Urea

scholarly journals Chemical Constituents from Artemisia annua and Vitex agnus-castus as New Aromatase Inhibitors: In-vitro and In-silico Studies

2020 ◽  
Vol 64 (4) ◽  
Author(s):  
Hend M. Dawood ◽  
Eman Shawky ◽  
Hala M. Hammoda ◽  
Aly M. Metwally ◽  
Reham S. Ibrahim
Keyword(s):  
Aromatase Inhibitors ◽  
Inhibitory Activity ◽  
Artemisia Annua ◽  
Chemical Constituents ◽  
Interaction Patterns ◽  
In Silico Studies ◽  
Agnus Castus ◽  
Ic50 Values ◽  
Trimethyl Ether

Abstract. Aromatase inhibitors are important in certain cancers such as breast cancer in postmenopausal women. In this study, eight constituents from Artemisia annua L. and Vitex agnus-castus L. were isolated and evaluated for their aromatase inhibitory activity using in-vitro fluorimetric assay. All tested compounds possessed moderate to strong inhibitory activity with β-sitosterol and myricetin-3,7,4'-trimethyl ether  being the most active with IC50 values of 0.13 and 0.25 μM, respectively. Compounds were subjected to induced fit docking (IFD) where β-sitosterol, possessed comparable interaction patterns to the natural co-crystallized ligand androstenedione.  Furthermore, Absorption, Distribution, Metabolism, Excretion and Toxicity (ADME&T)‎ properties of the compounds were evaluated revealing that all compounds' properties - except some of β- sitosterol related to solubility - lied within the acceptable range for human use, thereby considered as competent drug-like molecules. These findings could qualify β- sitosterol, myricetin-3,7,4'-trimethyl ether and domesticoside   as lead compounds for the development of new aromatase inhibitors.

scholarly journals (E)-1-(Furan-2-yl)-(substituted phenyl)prop-2-en-1-one Derivatives as Tyrosinase Inhibitors and Melanogenesis Inhibition: An In Vitro and In Silico Study

Molecules ◽  
2020 ◽  
Vol 25 (22) ◽  
pp. 5460
Author(s):  
Hee Jin Jung ◽  
Sang Gyun Noh ◽  
Il Young Ryu ◽  
Chaeun Park ◽  
Ji Young Lee ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Tyrosinase Inhibitory Activity ◽  
Melanocyte Stimulating Hormone ◽  
B16f10 Cells ◽  
In Silico Study ◽  
Allosteric Sites ◽  
Ic50 Values ◽  
Kinetics Of ◽  
Mixed Inhibition Type

A series of (E)-1-(furan-2-yl)prop-2-en-1-one derivatives (compounds 1–8) were synthesized and evaluated for their mushroom tyrosinase inhibitory activity. Among these series, compound 8 (2,4-dihydroxy group bearing benzylidene) showed potent tyrosinase inhibitory activity, with respective IC50 values of 0.0433 µM and 0.28 µM for the monophenolase and diphenolase as substrates in comparison to kojic acid as standard compound 19.97 µM and 33.47 µM. Moreover, the enzyme kinetics of compound 8 were determined to be of the mixed inhibition type and inhibition constant (Ki) values of 0.012 µM and 0.165 µM using the Lineweaver-Burk plot. Molecular docking results indicated that compound 8 can bind to the catalytic and allosteric sites 1 and 2 of tyrosinase to inhibit enzyme activity. The computational molecular dynamics analysis further revealed that compound 8 interacted with two residues in the tyrosinase active site pocket, such as ASN260 and MET280. In addition, compound 8 attenuated melanin synthesis and cellular tyrosinase activity, simulated by α-melanocyte-stimulating hormone and 1-methyl-3-isobutylxanthine. Compound 8 also decreased tyrosinase expressions in B16F10 cells. Based on in vitro and computational studies, we propose that compound 8 might be a worthy candidate for the development of an antipigmentation agent.

scholarly journals New Carbonic Anhydrase-II Inhibitors from Marine Macro Brown Alga Dictyopteris hoytii Supported by In Silico Studies

Molecules ◽  
2021 ◽  
Vol 26 (23) ◽  
pp. 7074
Author(s):  
Kashif Rafiq ◽  
Ajmal Khan ◽  
Najeeb Ur Rehman ◽  
Sobia Ahsan Halim ◽  
Majid Khan ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Inhibitory Activity ◽  
2D Nmr ◽  
Docking Studies ◽  
Carbonic Anhydrase Ii ◽  
Binding Behavior ◽  
In Silico Studies ◽  
Ic50 Values ◽  
First Time

In continuation of phytochemical investigations of the methanolic extract of Dictyopteris hoytii, we have obtained twelve compounds (1–12) through column chromatography. Herein, three compounds, namely, dimethyl 2-bromoterepthalate (3), dimethyl 2,6-dibromoterepthalate (4), and (E)-3-(4-(dimethoxymethyl)phenyl) acrylic acid (5) are isolated for the first time as a natural product, while the rest of the compounds (1, 2, 6–12) are known and isolated for the first time from this source. The structures of the isolated compounds were elucidated by advanced spectroscopic 1D and 2D NMR techniques including 1H, 13C, DEPT, HSQC, HMBC, COSY, NEOSY, and HR-MS and comparison with the reported literature. Furthermore, eight compounds (13–20) previously isolated by our group from the same source along with the currently isolated compounds (1–12) were screened against the CA-II enzyme. All compounds, except 6, 8, 14, and 17, were evaluated for in vitro bovine carbonic anhydrase-II (CA-II) inhibitory activity. Eventually, eleven compounds (1, 4, 5, 7, 9, 10, 12, 13, 15, 18, and 19) exhibited significant inhibitory activity against CA-II with IC50 values ranging from 13.4 to 71.6 μM. Additionally, the active molecules were subjected to molecular docking studies to predict the binding behavior of those compounds. It was observed that the compounds exhibit the inhibitory potential by specifically interacting with the ZN ion present in the active site of CA-II. In addition to ZN ion, two residues (His94 and Thr199) play an important role in binding with the compounds that possess a carboxylate group in their structure.

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