دورية أكاديمية
أعرض في EDS

Inhibition of soluble epoxide hydrolase by natural isothiocyanates.

التفاصيل البيبلوغرافية
العنوان: Inhibition of soluble epoxide hydrolase by natural isothiocyanates.
المؤلفون: Elbarbry F; School of Pharmacy, Pacific University, 222 SE 8th Ave, Ste. 451, Hillsboro, OR, 97123, USA. Electronic address: Fawzy.elbarbry@pacificu.edu., Espiritu MJ; School of Pharmacy, Pacific University, 222 SE 8th Ave, Ste. 451, Hillsboro, OR, 97123, USA., Soo K; School of Pharmacy, Pacific University, 222 SE 8th Ave, Ste. 451, Hillsboro, OR, 97123, USA., Yee B; School of Pharmacy, Pacific University, 222 SE 8th Ave, Ste. 451, Hillsboro, OR, 97123, USA., Taylor J; School of Pharmacy, Pacific University, 222 SE 8th Ave, Ste. 451, Hillsboro, OR, 97123, USA.
المصدر: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2024 Sep 17; Vol. 725, pp. 150261. Date of Electronic Publication: 2024 Jun 12.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: United States NLM ID: 0372516 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2104 (Electronic) Linking ISSN: 0006291X NLM ISO Abbreviation: Biochem Biophys Res Commun Subsets: MEDLINE
أسماء مطبوعة: Publication: <2002- >: San Diego, CA : Elsevier
Original Publication: New York, Academic Press.
مواضيع طبية MeSH: Epoxide Hydrolases*/antagonists & inhibitors , Epoxide Hydrolases*/metabolism , Epoxide Hydrolases*/chemistry , Isothiocyanates*/pharmacology , Isothiocyanates*/chemistry , Isothiocyanates*/metabolism , Molecular Docking Simulation* , Microsomes, Liver*/enzymology , Microsomes, Liver*/metabolism , Microsomes, Liver*/drug effects , Enzyme Inhibitors*/pharmacology , Enzyme Inhibitors*/chemistry, Humans ; Solubility
مستخلص: Goal: The long-term goal of our research is to develop safe and effective soluble epoxide hydrolase (sEH) inhibitors. The objective of this study is to evaluate the potency and selectivity of six natural isothiocyanates (ITCs) as sEH inhibitors.
Methods: Molecular docking was used to model likely interactions between the ligands and receptors. The sEH inhibitory activity was tested using a validated fluorescence-based assay and PHOME as a substrate. To evaluate their selectivity as sEH inhibitors, the inhibitory potential of the ITCs was determined on microsomal epoxide hydrolase (mEH) and cytochrome P450 (CYP) enzymes in human liver microsomes. Probe substrates such as styrene oxide (mEH substrate) and established substrates for CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4 were used in this study. The metabolites of these substrates were analyzed using validated LC-MS/MS and HPLC-UV assays.
Results: Molecular Docking revealed significant differences in binding site preference among the ITCs in silico and pointed to important interactions between the ligands and the catalytic residues of the sEH enzyme. In vitro, the ITCs showed varying degrees of sEH inhibition, but sulforaphane (SFN) and phenyl isothiocyanate (PITC) were the most potent inhibitors with IC 50 values of 3.65 and 7.5 μM, respectively. mEH was not significantly inhibited by any of the ITCs. Erucin and iberin were the only ITCs that did not inhibit the activity of any of the tested CYP enzymes.
Conclusion: Our results demonstrate that natural ITCs have the potential to offer safe, selective, and potent sEH inhibition.
Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
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معلومات مُعتمدة: R16 GM145589 United States GM NIGMS NIH HHS
فهرسة مساهمة: Keywords: Cytochrome P450; Enzyme inhibition; Hypertension; Isothiocyanates; Molecular docking; Soluble epoxide hydrolase
المشرفين على المادة: EC 3.3.2.- (Epoxide Hydrolases)
0 (Isothiocyanates)
0 (Enzyme Inhibitors)
تواريخ الأحداث: Date Created: 20240619 Date Completed: 20240704 Latest Revision: 20240723
رمز التحديث: 20240723
مُعرف محوري في PubMed: PMC11260514
DOI: 10.1016/j.bbrc.2024.150261
PMID: 38897040
قاعدة البيانات: MEDLINE
الوصف
تدمد:1090-2104
DOI:10.1016/j.bbrc.2024.150261