Discovery of new thymol-3,4-disubstituted thiazole hybrids as dual COX-2/5-LOX inhibitors with in vivo proof
New thymol–3,4-disubstitutedthiazole hybrids were synthesised as dual COX-2/5-LOX inhibitors. Compounds 6b, 6d, 6e, and 6f displayed in vitro inhibitory activity against COX-2 (IC50= 0.037, 0.042, 0.046, and 0.039 µM) nearly equal to celecoxib (IC50= 0.045 µM). 6b, 6d, and 6f showed SI (379, 341, an...
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Taylor & Francis Group
2024-12-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/14756366.2024.2309171 |
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| author | Mostafa M. M. El-Miligy Ahmed K. Al-Kubeisi Rasha A. Nassra Saad R. El-Zemity Aly A. Hazzaa |
| author_facet | Mostafa M. M. El-Miligy Ahmed K. Al-Kubeisi Rasha A. Nassra Saad R. El-Zemity Aly A. Hazzaa |
| author_sort | Mostafa M. M. El-Miligy |
| collection | DOAJ |
| description | New thymol–3,4-disubstitutedthiazole hybrids were synthesised as dual COX-2/5-LOX inhibitors. Compounds 6b, 6d, 6e, and 6f displayed in vitro inhibitory activity against COX-2 (IC50= 0.037, 0.042, 0.046, and 0.039 µM) nearly equal to celecoxib (IC50= 0.045 µM). 6b, 6d, and 6f showed SI (379, 341, and 374, respectively) higher than that of celecoxib (327). 6a–l elicited in vitro 5-LOX inhibitory activity higher than quercetin. 6a–f, 6i–l, 7a, and 7c possessed in vivo inhibition of formalin induced paw edoema higher than celecoxib. 6a, 6b, 6f, 6h–l, and 7b showed gastrointestinal safety profile as celecoxib and diclofenac sodium in the population of fasted rats. Induced fit docking and molecular dynamics simulation predicted good fitting of 6b and 6f without changing the packing and globularity of the apo protein. In conclusion, 6b and 6f achieved the target goal as multitarget inhibitors of inflammation. |
| format | Article |
| id | doaj-art-fec79da2057e482d91a08ba9a8c001f5 |
| institution | Kabale University |
| issn | 1475-6366 1475-6374 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
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| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj-art-fec79da2057e482d91a08ba9a8c001f52024-12-26T09:30:44ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742024-12-0139110.1080/14756366.2024.2309171Discovery of new thymol-3,4-disubstituted thiazole hybrids as dual COX-2/5-LOX inhibitors with in vivo proofMostafa M. M. El-Miligy0Ahmed K. Al-Kubeisi1Rasha A. Nassra2Saad R. El-Zemity3Aly A. Hazzaa4Pharmaceutical Chemistry Department, Faculty of Pharmacy, Alexandria University, Alexandria, EgyptPharmacy Department, Al-Maarif University College, Ramadi, Anbar, IraqMedical Biochemistry Department, Faculty of Medicine, Alexandria University, Alexandria, EgyptDepartment of Chemistry and Technology of Pesticides, Faculty of Agriculture, Alexandria University, Alexandria, EgyptPharmaceutical Chemistry Department, Faculty of Pharmacy, Alexandria University, Alexandria, EgyptNew thymol–3,4-disubstitutedthiazole hybrids were synthesised as dual COX-2/5-LOX inhibitors. Compounds 6b, 6d, 6e, and 6f displayed in vitro inhibitory activity against COX-2 (IC50= 0.037, 0.042, 0.046, and 0.039 µM) nearly equal to celecoxib (IC50= 0.045 µM). 6b, 6d, and 6f showed SI (379, 341, and 374, respectively) higher than that of celecoxib (327). 6a–l elicited in vitro 5-LOX inhibitory activity higher than quercetin. 6a–f, 6i–l, 7a, and 7c possessed in vivo inhibition of formalin induced paw edoema higher than celecoxib. 6a, 6b, 6f, 6h–l, and 7b showed gastrointestinal safety profile as celecoxib and diclofenac sodium in the population of fasted rats. Induced fit docking and molecular dynamics simulation predicted good fitting of 6b and 6f without changing the packing and globularity of the apo protein. In conclusion, 6b and 6f achieved the target goal as multitarget inhibitors of inflammation.https://www.tandfonline.com/doi/10.1080/14756366.2024.2309171thiazoleanti-inflammatorydual COX-2/5-LOX inhibitorsinduced fit dockingmolecular dynamic simulation |
| spellingShingle | Mostafa M. M. El-Miligy Ahmed K. Al-Kubeisi Rasha A. Nassra Saad R. El-Zemity Aly A. Hazzaa Discovery of new thymol-3,4-disubstituted thiazole hybrids as dual COX-2/5-LOX inhibitors with in vivo proof Journal of Enzyme Inhibition and Medicinal Chemistry thiazole anti-inflammatory dual COX-2/5-LOX inhibitors induced fit docking molecular dynamic simulation |
| title | Discovery of new thymol-3,4-disubstituted thiazole hybrids as dual COX-2/5-LOX inhibitors with in vivo proof |
| title_full | Discovery of new thymol-3,4-disubstituted thiazole hybrids as dual COX-2/5-LOX inhibitors with in vivo proof |
| title_fullStr | Discovery of new thymol-3,4-disubstituted thiazole hybrids as dual COX-2/5-LOX inhibitors with in vivo proof |
| title_full_unstemmed | Discovery of new thymol-3,4-disubstituted thiazole hybrids as dual COX-2/5-LOX inhibitors with in vivo proof |
| title_short | Discovery of new thymol-3,4-disubstituted thiazole hybrids as dual COX-2/5-LOX inhibitors with in vivo proof |
| title_sort | discovery of new thymol 3 4 disubstituted thiazole hybrids as dual cox 2 5 lox inhibitors with in vivo proof |
| topic | thiazole anti-inflammatory dual COX-2/5-LOX inhibitors induced fit docking molecular dynamic simulation |
| url | https://www.tandfonline.com/doi/10.1080/14756366.2024.2309171 |
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