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Novel Group of Imidazole Derivatives as Atypical Selective Cyclooxygenase-2 Inhibitors: Design, Synthesis and Biological Evaluation
In this study, a new series of 5-substituted 1-benzyl-2-(methylsulfonyl)-1-H-imidazole with atypical structure-activity relationship was designed, synthesized, and biological evaluated as selective cyclooxygenase-2 inhibitors. Docking studies revealed that although the pharmacophoric substitute of t...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Shaheed Beheshti University of Medical Sciences
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6447865/ https://www.ncbi.nlm.nih.gov/pubmed/31011344 |
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author | Kiani, Azin Rezaee, Elham Tabatabai, Sayyed Abbas |
author_facet | Kiani, Azin Rezaee, Elham Tabatabai, Sayyed Abbas |
author_sort | Kiani, Azin |
collection | PubMed |
description | In this study, a new series of 5-substituted 1-benzyl-2-(methylsulfonyl)-1-H-imidazole with atypical structure-activity relationship was designed, synthesized, and biological evaluated as selective cyclooxygenase-2 inhibitors. Docking studies revealed that although the pharmacophoric substitute of the compound 5b, methylsulfonyl group, has been directly attached to the central ring, it is in the same direction of the sulfonamide group of Celecoxib, a known selective cyclooxygenase-2 inhibitor. Therefore effective hydrogen binding with Arg513 is established. Also, additional hydrogen binding could form between NH of anilino moiety of the 5b and Arg120. All of the compounds had selective inhibitory activity against cyclooxygenase-2 in micromolar concentrations comparable with the reference, Celecoxibe. Finally, compound 5b with the selectivity index 115 and IC(50) of 0.71 µM against cyclooxygenase-2 was the most potent one. |
format | Online Article Text |
id | pubmed-6447865 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Shaheed Beheshti University of Medical Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-64478652019-04-22 Novel Group of Imidazole Derivatives as Atypical Selective Cyclooxygenase-2 Inhibitors: Design, Synthesis and Biological Evaluation Kiani, Azin Rezaee, Elham Tabatabai, Sayyed Abbas Iran J Pharm Res Original Article In this study, a new series of 5-substituted 1-benzyl-2-(methylsulfonyl)-1-H-imidazole with atypical structure-activity relationship was designed, synthesized, and biological evaluated as selective cyclooxygenase-2 inhibitors. Docking studies revealed that although the pharmacophoric substitute of the compound 5b, methylsulfonyl group, has been directly attached to the central ring, it is in the same direction of the sulfonamide group of Celecoxib, a known selective cyclooxygenase-2 inhibitor. Therefore effective hydrogen binding with Arg513 is established. Also, additional hydrogen binding could form between NH of anilino moiety of the 5b and Arg120. All of the compounds had selective inhibitory activity against cyclooxygenase-2 in micromolar concentrations comparable with the reference, Celecoxibe. Finally, compound 5b with the selectivity index 115 and IC(50) of 0.71 µM against cyclooxygenase-2 was the most potent one. Shaheed Beheshti University of Medical Sciences 2018 /pmc/articles/PMC6447865/ /pubmed/31011344 Text en This is an Open Access article distributed under the terms of the Creative Commons Attribution License, (http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Kiani, Azin Rezaee, Elham Tabatabai, Sayyed Abbas Novel Group of Imidazole Derivatives as Atypical Selective Cyclooxygenase-2 Inhibitors: Design, Synthesis and Biological Evaluation |
title | Novel Group of Imidazole Derivatives as Atypical Selective Cyclooxygenase-2 Inhibitors: Design, Synthesis and Biological Evaluation |
title_full | Novel Group of Imidazole Derivatives as Atypical Selective Cyclooxygenase-2 Inhibitors: Design, Synthesis and Biological Evaluation |
title_fullStr | Novel Group of Imidazole Derivatives as Atypical Selective Cyclooxygenase-2 Inhibitors: Design, Synthesis and Biological Evaluation |
title_full_unstemmed | Novel Group of Imidazole Derivatives as Atypical Selective Cyclooxygenase-2 Inhibitors: Design, Synthesis and Biological Evaluation |
title_short | Novel Group of Imidazole Derivatives as Atypical Selective Cyclooxygenase-2 Inhibitors: Design, Synthesis and Biological Evaluation |
title_sort | novel group of imidazole derivatives as atypical selective cyclooxygenase-2 inhibitors: design, synthesis and biological evaluation |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6447865/ https://www.ncbi.nlm.nih.gov/pubmed/31011344 |
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