Synthesis, Biological Activity, and Molecular Modeling Studies of Pyrazole and Triazole Derivatives as Selective COX-2 Inhibitors
Series of diaryl-based pyrazole and triazole derivatives were designed and synthesized in a facile synthetic approach in order to produce selective COX-2 inhibitor. These series of derivatives were synthesized by different reactions like Vilsmeier–Haack reaction and click reaction. In vitro COX-1 an...
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| Format: | Article |
| Language: | English |
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Wiley
2020-01-01
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| Series: | Journal of Chemistry |
| Online Access: | http://dx.doi.org/10.1155/2020/6393428 |
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| author | Mohyeddin Assali Murad Abualhasan Hadeel Sawaftah Mohammed Hawash Ahmed Mousa |
| author_facet | Mohyeddin Assali Murad Abualhasan Hadeel Sawaftah Mohammed Hawash Ahmed Mousa |
| author_sort | Mohyeddin Assali |
| collection | DOAJ |
| description | Series of diaryl-based pyrazole and triazole derivatives were designed and synthesized in a facile synthetic approach in order to produce selective COX-2 inhibitor. These series of derivatives were synthesized by different reactions like Vilsmeier–Haack reaction and click reaction. In vitro COX-1 and COX-2 inhibition studies showed that five compounds were potent and selective inhibitors of the COX-2 isozyme with IC50 values in 0.551–0.002 μM range. In the diarylpyrazole derivatives, compound 4b showed the best inhibitory activity against COX-2 with IC50 = 0.017 μM as one of the N-aromatic rings was substituted with sulfonamide and the other aromatic ring was unsubstituted. However, when the N-aromatic ring was substituted with sulfonamide and the other aromatic ring was substituted with sulfone (compound 4d), best COX-2 selectivity was achieved (IC50 = 0.098 μM, SI = 54.847). In the diaryltriazole derivatives, compound 15a showed the best inhibitory activity in comparison to all synthesized compounds including the reference celecoxib with IC50 = 0.002 μM and SI = 162.5 as it could better fit the extra hydrophobic pocket which is present in the COX-2 enzyme. Moreover, the docking study supports the obtained SAR data and binding similarities and differences on both isozymes. |
| format | Article |
| id | doaj-art-bd0728f3030d47be8b086700b4882a41 |
| institution | Kabale University |
| issn | 2090-9063 2090-9071 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Chemistry |
| spelling | doaj-art-bd0728f3030d47be8b086700b4882a412025-02-03T01:25:50ZengWileyJournal of Chemistry2090-90632090-90712020-01-01202010.1155/2020/63934286393428Synthesis, Biological Activity, and Molecular Modeling Studies of Pyrazole and Triazole Derivatives as Selective COX-2 InhibitorsMohyeddin Assali0Murad Abualhasan1Hadeel Sawaftah2Mohammed Hawash3Ahmed Mousa4Department of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, P. O. Box 7, Nablus, State of PalestineDepartment of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, P. O. Box 7, Nablus, State of PalestineDepartment of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, P. O. Box 7, Nablus, State of PalestineDepartment of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, P. O. Box 7, Nablus, State of PalestineDepartment of Biomedical Sciences, Faculty of Medicine and Health Sciences, An-Najah National University, P. O. Box 7, Nablus, State of PalestineSeries of diaryl-based pyrazole and triazole derivatives were designed and synthesized in a facile synthetic approach in order to produce selective COX-2 inhibitor. These series of derivatives were synthesized by different reactions like Vilsmeier–Haack reaction and click reaction. In vitro COX-1 and COX-2 inhibition studies showed that five compounds were potent and selective inhibitors of the COX-2 isozyme with IC50 values in 0.551–0.002 μM range. In the diarylpyrazole derivatives, compound 4b showed the best inhibitory activity against COX-2 with IC50 = 0.017 μM as one of the N-aromatic rings was substituted with sulfonamide and the other aromatic ring was unsubstituted. However, when the N-aromatic ring was substituted with sulfonamide and the other aromatic ring was substituted with sulfone (compound 4d), best COX-2 selectivity was achieved (IC50 = 0.098 μM, SI = 54.847). In the diaryltriazole derivatives, compound 15a showed the best inhibitory activity in comparison to all synthesized compounds including the reference celecoxib with IC50 = 0.002 μM and SI = 162.5 as it could better fit the extra hydrophobic pocket which is present in the COX-2 enzyme. Moreover, the docking study supports the obtained SAR data and binding similarities and differences on both isozymes.http://dx.doi.org/10.1155/2020/6393428 |
| spellingShingle | Mohyeddin Assali Murad Abualhasan Hadeel Sawaftah Mohammed Hawash Ahmed Mousa Synthesis, Biological Activity, and Molecular Modeling Studies of Pyrazole and Triazole Derivatives as Selective COX-2 Inhibitors Journal of Chemistry |
| title | Synthesis, Biological Activity, and Molecular Modeling Studies of Pyrazole and Triazole Derivatives as Selective COX-2 Inhibitors |
| title_full | Synthesis, Biological Activity, and Molecular Modeling Studies of Pyrazole and Triazole Derivatives as Selective COX-2 Inhibitors |
| title_fullStr | Synthesis, Biological Activity, and Molecular Modeling Studies of Pyrazole and Triazole Derivatives as Selective COX-2 Inhibitors |
| title_full_unstemmed | Synthesis, Biological Activity, and Molecular Modeling Studies of Pyrazole and Triazole Derivatives as Selective COX-2 Inhibitors |
| title_short | Synthesis, Biological Activity, and Molecular Modeling Studies of Pyrazole and Triazole Derivatives as Selective COX-2 Inhibitors |
| title_sort | synthesis biological activity and molecular modeling studies of pyrazole and triazole derivatives as selective cox 2 inhibitors |
| url | http://dx.doi.org/10.1155/2020/6393428 |
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