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Soluble epoxide hydrolase (sEH) is an enzyme targeted for the treatment of inflammation and cardiovascular diseases. Activated inflammatory cells produce nitric oxide (NO), which induces oxidative stress and exacerbates inflammation. We identify an inhibitor able to suppress sEH and thus NO production. Five flavonoids - isolated from flowers were evaluated for their abilities to inhibit sEH with IC values of 12.1 ± 0.1 to 62.8 ± 1.8 µM and for their effects on enzyme kinetics. A simulation study using computational chemistry was conducted as well. Furthermore, five inhibitors (-) were confirmed to suppress NO levels at 10 µM. The results showed that flavonoids - exhibited inhibitory activity in all tests, with compound exhibiting the most significant efficacy. Thus, in the development of anti-inflammatory inhibitors, compound is a promising natural candidate.
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http://dx.doi.org/10.3390/ijms25084357 | DOI Listing |
Genetic studies have linked (encoding soluble epoxide hydrolase, sEH) and (encoding cyclooxygenase-2, COX-2) to Alzheimer's disease (AD). Elevated levels of sEH and COX-2 found in AD patients and animals suggest their involvement in neurodegeneration, glial activation, vascular dysfunction, and inflammation. This study evaluated the effects of a new dual sEH/COX-2 inhibitor, PTUPB, on cerebrovascular function and cognition in TgF344-AD rats.
View Article and Find Full Text PDFChem Biol Drug Des
September 2025
Department of Pharmacy, Birla Institute of Technology and Science (BITS) Pilani, Medchal, Telangana, India.
A novel series of triazole-linked indole derivatives was designed, synthesized, and evaluated as soluble epoxide hydrolase inhibitors (sEHIs) for their potential anticancer activity. These compounds exhibit strong binding affinity within the hydrophobic pockets of sEH, with compounds 9a and 9b emerging as the most potent inhibitors, achieving IC₅₀ values of 0.270 ± 0.
View Article and Find Full Text PDFACS Omega
August 2025
Institute of Chemistry, Universidade Federal do Rio Grande do Sul, Av. Bento Gonçalves, 9500, Porto Alegre, RS 91501-970, Brazil.
This review examines the role of ionic liquids (ILs) in the catalytic carbonation of epoxides for the synthesis of cyclic carbonates, focusing on the key factors that influence reaction efficiency. The nucleophilicity and basicity of the anions in IL catalysts are highlighted as critical components for promoting the cycloaddition reaction with CO. The solubility and ionicity of the ILs also significantly affect the reaction, with higher ionicity leading to better solubilization and catalytic performance.
View Article and Find Full Text PDFJ Transl Med
August 2025
School of Stomatology, Dalian Medical University, No. 9 West Section, Lvshun South Road, Dalian, 116044, P.R. China.
Background: Macrophage immunomodulation has emerged as a novel intervention and therapeutic strategy for temporomandibular joint osteoarthritis (TMJOA), potentially serving as a key approach for reducing synovial inflammation and promoting cartilage repair. The soluble epoxide hydrolase inhibitor (sEHi), TPPU, has shown potential therapeutic effects against inflammatory diseases and osteogenesis by elevating endogenous Epoxyeicosatrienoic acids (EETs). However, it remains largely unknown whether TPPU can reduce inflammation and cartilage degradation in the TMJOA.
View Article and Find Full Text PDFACS Med Chem Lett
August 2025
Smith, Gambrell & Russell LLP, 1105 W. Peachtree Street NE, Atlanta, Georgia 30309, United States.
Provided herein are novel spiropiperidine urea-derived compounds as soluble epoxide hydrolase inhibitors, pharmaceutical compositions, use of such compounds in treating diabetic retinopathy, and processes for preparing such compounds.
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