Cargando…
Design, Synthesis and Biological Evaluation of New 5,5-Diarylhydantoin Derivatives as Selective Cyclooxygenase-2 Inhibitors
A new group of 5,5-diarylhydantoin derivatives bearing a methylsulfonyl COX-2 pharmacophore at the para position of the C-5 phenyl ring were designed and synthesized as selective COX-2 inhibitors. In vitro COX-1/COX-2 inhibition structure-activity relationships identified 5-[4-(methylsulfonyl)phenyl...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Österreichische Apotheker-Verlagsgesellschaft
2011
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3163375/ https://www.ncbi.nlm.nih.gov/pubmed/21886896 http://dx.doi.org/10.3797/scipharm.1104-20 |
_version_ | 1782210940896280576 |
---|---|
author | Zarghi, Afshin Javid, Farin Sattary Ghodsi, Razieh Dadrass, Orkideh G. Daraei, Bahram Hedayati, Mehdi |
author_facet | Zarghi, Afshin Javid, Farin Sattary Ghodsi, Razieh Dadrass, Orkideh G. Daraei, Bahram Hedayati, Mehdi |
author_sort | Zarghi, Afshin |
collection | PubMed |
description | A new group of 5,5-diarylhydantoin derivatives bearing a methylsulfonyl COX-2 pharmacophore at the para position of the C-5 phenyl ring were designed and synthesized as selective COX-2 inhibitors. In vitro COX-1/COX-2 inhibition structure-activity relationships identified 5-[4-(methylsulfonyl)phenyl]-5-phenyl-hydantoin (4) as a highly potent and selective COX-2 inhibitor (COX-2 IC(50) = 0.077 μM; selectivity index > 1298). It was more selective than the reference drug celecoxib (COX-2 IC(50) = 0.060 μM; selectivity index = 405). A molecular modeling study where 4 was docked in the binding site of COX-2 indicated that the p-MeSO(2) COX-2 pharmacophore group on the C-5 phenyl ring is oriented in the vicinity of the COX-2 secondary pocket. The results of this study showed that the type of substituent on the N-3 hydantoin ring substituent is important for COX-2 inhibitory activity. |
format | Online Article Text |
id | pubmed-3163375 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Österreichische Apotheker-Verlagsgesellschaft |
record_format | MEDLINE/PubMed |
spelling | pubmed-31633752011-09-01 Design, Synthesis and Biological Evaluation of New 5,5-Diarylhydantoin Derivatives as Selective Cyclooxygenase-2 Inhibitors Zarghi, Afshin Javid, Farin Sattary Ghodsi, Razieh Dadrass, Orkideh G. Daraei, Bahram Hedayati, Mehdi Sci Pharm Research Article A new group of 5,5-diarylhydantoin derivatives bearing a methylsulfonyl COX-2 pharmacophore at the para position of the C-5 phenyl ring were designed and synthesized as selective COX-2 inhibitors. In vitro COX-1/COX-2 inhibition structure-activity relationships identified 5-[4-(methylsulfonyl)phenyl]-5-phenyl-hydantoin (4) as a highly potent and selective COX-2 inhibitor (COX-2 IC(50) = 0.077 μM; selectivity index > 1298). It was more selective than the reference drug celecoxib (COX-2 IC(50) = 0.060 μM; selectivity index = 405). A molecular modeling study where 4 was docked in the binding site of COX-2 indicated that the p-MeSO(2) COX-2 pharmacophore group on the C-5 phenyl ring is oriented in the vicinity of the COX-2 secondary pocket. The results of this study showed that the type of substituent on the N-3 hydantoin ring substituent is important for COX-2 inhibitory activity. Österreichische Apotheker-Verlagsgesellschaft 2011 2011-07-25 /pmc/articles/PMC3163375/ /pubmed/21886896 http://dx.doi.org/10.3797/scipharm.1104-20 Text en © Zarghi et al.; licensee Österreichische Apotheker-Verlagsgesellschaft m. b. H., Vienna, Austria. 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 | Research Article Zarghi, Afshin Javid, Farin Sattary Ghodsi, Razieh Dadrass, Orkideh G. Daraei, Bahram Hedayati, Mehdi Design, Synthesis and Biological Evaluation of New 5,5-Diarylhydantoin Derivatives as Selective Cyclooxygenase-2 Inhibitors |
title | Design, Synthesis and Biological Evaluation of New 5,5-Diarylhydantoin Derivatives as Selective Cyclooxygenase-2 Inhibitors |
title_full | Design, Synthesis and Biological Evaluation of New 5,5-Diarylhydantoin Derivatives as Selective Cyclooxygenase-2 Inhibitors |
title_fullStr | Design, Synthesis and Biological Evaluation of New 5,5-Diarylhydantoin Derivatives as Selective Cyclooxygenase-2 Inhibitors |
title_full_unstemmed | Design, Synthesis and Biological Evaluation of New 5,5-Diarylhydantoin Derivatives as Selective Cyclooxygenase-2 Inhibitors |
title_short | Design, Synthesis and Biological Evaluation of New 5,5-Diarylhydantoin Derivatives as Selective Cyclooxygenase-2 Inhibitors |
title_sort | design, synthesis and biological evaluation of new 5,5-diarylhydantoin derivatives as selective cyclooxygenase-2 inhibitors |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3163375/ https://www.ncbi.nlm.nih.gov/pubmed/21886896 http://dx.doi.org/10.3797/scipharm.1104-20 |
work_keys_str_mv | AT zarghiafshin designsynthesisandbiologicalevaluationofnew55diarylhydantoinderivativesasselectivecyclooxygenase2inhibitors AT javidfarinsattary designsynthesisandbiologicalevaluationofnew55diarylhydantoinderivativesasselectivecyclooxygenase2inhibitors AT ghodsirazieh designsynthesisandbiologicalevaluationofnew55diarylhydantoinderivativesasselectivecyclooxygenase2inhibitors AT dadrassorkidehg designsynthesisandbiologicalevaluationofnew55diarylhydantoinderivativesasselectivecyclooxygenase2inhibitors AT daraeibahram designsynthesisandbiologicalevaluationofnew55diarylhydantoinderivativesasselectivecyclooxygenase2inhibitors AT hedayatimehdi designsynthesisandbiologicalevaluationofnew55diarylhydantoinderivativesasselectivecyclooxygenase2inhibitors |