Anti-Inflammatory Activity of Soluble Epoxide Hydrolase Inhibitors Based on Selenoureas Bearing an Adamantane Moiety.

Autor: Burmistrov V; Department of Entomology and Nematology, Comprehensive Cancer Center, University of California, Davis, CA 95616, USA.; Department of Chemistry, Technology and Equipment of Chemical Industry, Volzhsky Polytechnic Institute (Branch), Volgograd State Technical University, 404121 Volzhsky, Russia., Morisseau C; Department of Entomology and Nematology, Comprehensive Cancer Center, University of California, Davis, CA 95616, USA., Babkov DA; Department of Pharmacology & Bioinformatics, Scientific Center for Innovative Drugs, Volgograd State Medical University, 400131 Volgograd, Russia., Golubeva T; Institute of Cytology and Genetics SB RAS, 630090 Novosibirsk, Russia.; Specialized Educational Scientific Center, Novosibirsk State University, 630090 Novosibirsk, Russia., Pitushkin D; Department of Chemistry, Technology and Equipment of Chemical Industry, Volzhsky Polytechnic Institute (Branch), Volgograd State Technical University, 404121 Volzhsky, Russia., Sokolova EV; Department of Pharmacology & Bioinformatics, Scientific Center for Innovative Drugs, Volgograd State Medical University, 400131 Volgograd, Russia., Vasipov V; N.I. Vavilov All-Russian Institute of Plant Genetic Resources, 42, 44, Bolshaya Morskaya Street, 190000 St. Petersburg, Russia., Kuznetsov Y; Department of Chemistry, Technology and Equipment of Chemical Industry, Volzhsky Polytechnic Institute (Branch), Volgograd State Technical University, 404121 Volzhsky, Russia., Bazhenov SV; Research Center for Molecular Mechanisms of Aging and Age-Related Diseases, Moscow Institute of Physics and Technology, Institutsky Lane 9, 141700 Dolgoprudny, Moscow Region, Russia., Novoyatlova US; Research Center for Molecular Mechanisms of Aging and Age-Related Diseases, Moscow Institute of Physics and Technology, Institutsky Lane 9, 141700 Dolgoprudny, Moscow Region, Russia., Bondarev NA; Research Center for Molecular Mechanisms of Aging and Age-Related Diseases, Moscow Institute of Physics and Technology, Institutsky Lane 9, 141700 Dolgoprudny, Moscow Region, Russia., Manukhov IV; Research Center for Molecular Mechanisms of Aging and Age-Related Diseases, Moscow Institute of Physics and Technology, Institutsky Lane 9, 141700 Dolgoprudny, Moscow Region, Russia., Osipova V; Toxicology Research Group of Southern Scientific Centre of Russian Academy of Science, 41 Chekhova Str., 344006 Rostov-on-Don, Russia., Berberova N; Department of Chemistry, Astrakhan State Technical University, 16 Tatisheva Street, 414056 Astrakhan, Russia., Spasov AA; Department of Pharmacology & Bioinformatics, Scientific Center for Innovative Drugs, Volgograd State Medical University, 400131 Volgograd, Russia., Butov GM; Department of Chemistry, Technology and Equipment of Chemical Industry, Volzhsky Polytechnic Institute (Branch), Volgograd State Technical University, 404121 Volzhsky, Russia., Hammock BD; Department of Entomology and Nematology, Comprehensive Cancer Center, University of California, Davis, CA 95616, USA.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2022 Sep 14; Vol. 23 (18). Date of Electronic Publication: 2022 Sep 14.
DOI: 10.3390/ijms231810710
Abstrakt: The inhibitory potency of the series of inhibitors of the soluble epoxide hydrolase (sEH) based on the selenourea moiety and containing adamantane and aromatic lipophilic groups ranges from 34.3 nM to 1.2 μM. The most active compound 5d possesses aliphatic spacers between the selenourea group and lipophilic fragments. Synthesized compounds were tested against the LPS-induced activation of primary murine macrophages. The most prominent anti-inflammatory activity, defined as a suppression of nitric oxide synthesis by LPS-stimulated macrophages, was demonstrated for compounds 4a and 5b . The cytotoxicity of the obtained substances was studied using human neuroblastoma and fibroblast cell cultures. Using these cell assays, the cytotoxic concentration for 4a was 4.7-18.4 times higher than the effective anti-inflammatory concentration. The genotoxicity and the ability to induce oxidative stress was studied using bacterial lux -biosensors. Substance 4a does not exhibit genotoxic properties, but it can cause oxidative stress at concentrations above 50 µM. Put together, the data showed the efficacy and safety of compound 4a .
Databáze: MEDLINE
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