Synthesis, Evaluation of Enzyme Inhibition and Redox Properties of Potential Dual COX-2 and 5-LOX Inhibitors
Аутори
Bošković, JelenaDobričić, Vladimir
Mihajlović, Marija
Kotur-Stevuljević, Jelena
Čudina, Olivera
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
Various dual inhibitors of COX-2 and 5-LOX enzymes have been developed so far in order to obtain more effective and safer anti-inflammatory drugs. The aim of this study was to design and synthesize new dual COX-2 and 5-LOX inhibitors, and to evaluate their enzyme inhibition potential and redox properties. Thirteen compounds (1–13) were designed taking into account structural requirements for dual COX-2 and 5-LOX inhibition and antioxidant activity, synthesized, and structurally characterized. These compounds can be classified as N-hydroxyurea derivatives (1, 2 and 3), 3,5-di-tert-butylphenol derivatives (4, 5, 6, 7 and 13), urea derivatives (8, 9 and 10) and “type B hydroxamic acids” (11 and 12). COX-1, COX-2 and 5-LOX inhibitory activities were evaluated using fluorometric inhibitor screening kits. The evaluation of the redox activity of newly synthesized compounds was performed in vitro in the human serum pool using redox status tests.
The prooxidative score, the antioxidative score... and the oxy-score were calculated. Seven out of thirteen synthesized compounds (1, 2, 3, 5, 6, 11 and 12) proved to be dual COX-2 and 5-LOX inhibitors. These compounds expressed good COX-2/COX-1 selectivity. Moreover, dual inhibitors 1, 3, 5, 11 and 12 showed good antioxidant properties.
Кључне речи:
dual COX-2 and 5-LOX inhibitors / dual COX-2 and 5-LOX inhibitors / N-hydroxyurea derivatives / redox activity / urea derivatives / “type B hydroxamic acids”Извор:
Pharmaceuticals, 2023, 16, 4Издавач:
- MDPI
Финансирање / пројекти:
- InfCanPlay - Utilization of interplay between inflammation and cancer in the development of compounds with anticancer activity (RS-ScienceFundRS-Ideje-7739840)
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200161 (Универзитет у Београду, Фармацеутски факултет) (RS-MESTD-inst-2020-200161)
DOI: https://doi.org/10.3390/ph16040549
ISSN: 1424-8247
PubMed: 37111306
WoS: 000976483500001
Scopus: 2-s2.0-85154589153
Институција/група
PharmacyTY - JOUR AU - Bošković, Jelena AU - Dobričić, Vladimir AU - Mihajlović, Marija AU - Kotur-Stevuljević, Jelena AU - Čudina, Olivera PY - 2023 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4755 AB - Various dual inhibitors of COX-2 and 5-LOX enzymes have been developed so far in order to obtain more effective and safer anti-inflammatory drugs. The aim of this study was to design and synthesize new dual COX-2 and 5-LOX inhibitors, and to evaluate their enzyme inhibition potential and redox properties. Thirteen compounds (1–13) were designed taking into account structural requirements for dual COX-2 and 5-LOX inhibition and antioxidant activity, synthesized, and structurally characterized. These compounds can be classified as N-hydroxyurea derivatives (1, 2 and 3), 3,5-di-tert-butylphenol derivatives (4, 5, 6, 7 and 13), urea derivatives (8, 9 and 10) and “type B hydroxamic acids” (11 and 12). COX-1, COX-2 and 5-LOX inhibitory activities were evaluated using fluorometric inhibitor screening kits. The evaluation of the redox activity of newly synthesized compounds was performed in vitro in the human serum pool using redox status tests. The prooxidative score, the antioxidative score and the oxy-score were calculated. Seven out of thirteen synthesized compounds (1, 2, 3, 5, 6, 11 and 12) proved to be dual COX-2 and 5-LOX inhibitors. These compounds expressed good COX-2/COX-1 selectivity. Moreover, dual inhibitors 1, 3, 5, 11 and 12 showed good antioxidant properties. PB - MDPI T2 - Pharmaceuticals T1 - Synthesis, Evaluation of Enzyme Inhibition and Redox Properties of Potential Dual COX-2 and 5-LOX Inhibitors VL - 16 IS - 4 DO - https://doi.org/10.3390/ph16040549 ER -
@article{ author = "Bošković, Jelena and Dobričić, Vladimir and Mihajlović, Marija and Kotur-Stevuljević, Jelena and Čudina, Olivera", year = "2023", abstract = "Various dual inhibitors of COX-2 and 5-LOX enzymes have been developed so far in order to obtain more effective and safer anti-inflammatory drugs. The aim of this study was to design and synthesize new dual COX-2 and 5-LOX inhibitors, and to evaluate their enzyme inhibition potential and redox properties. Thirteen compounds (1–13) were designed taking into account structural requirements for dual COX-2 and 5-LOX inhibition and antioxidant activity, synthesized, and structurally characterized. These compounds can be classified as N-hydroxyurea derivatives (1, 2 and 3), 3,5-di-tert-butylphenol derivatives (4, 5, 6, 7 and 13), urea derivatives (8, 9 and 10) and “type B hydroxamic acids” (11 and 12). COX-1, COX-2 and 5-LOX inhibitory activities were evaluated using fluorometric inhibitor screening kits. The evaluation of the redox activity of newly synthesized compounds was performed in vitro in the human serum pool using redox status tests. The prooxidative score, the antioxidative score and the oxy-score were calculated. Seven out of thirteen synthesized compounds (1, 2, 3, 5, 6, 11 and 12) proved to be dual COX-2 and 5-LOX inhibitors. These compounds expressed good COX-2/COX-1 selectivity. Moreover, dual inhibitors 1, 3, 5, 11 and 12 showed good antioxidant properties.", publisher = "MDPI", journal = "Pharmaceuticals", title = "Synthesis, Evaluation of Enzyme Inhibition and Redox Properties of Potential Dual COX-2 and 5-LOX Inhibitors", volume = "16", number = "4", doi = "https://doi.org/10.3390/ph16040549" }
Bošković, J., Dobričić, V., Mihajlović, M., Kotur-Stevuljević, J.,& Čudina, O.. (2023). Synthesis, Evaluation of Enzyme Inhibition and Redox Properties of Potential Dual COX-2 and 5-LOX Inhibitors. in Pharmaceuticals MDPI., 16(4). https://doi.org/https://doi.org/10.3390/ph16040549
Bošković J, Dobričić V, Mihajlović M, Kotur-Stevuljević J, Čudina O. Synthesis, Evaluation of Enzyme Inhibition and Redox Properties of Potential Dual COX-2 and 5-LOX Inhibitors. in Pharmaceuticals. 2023;16(4). doi:https://doi.org/10.3390/ph16040549 .
Bošković, Jelena, Dobričić, Vladimir, Mihajlović, Marija, Kotur-Stevuljević, Jelena, Čudina, Olivera, "Synthesis, Evaluation of Enzyme Inhibition and Redox Properties of Potential Dual COX-2 and 5-LOX Inhibitors" in Pharmaceuticals, 16, no. 4 (2023), https://doi.org/https://doi.org/10.3390/ph16040549 . .