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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...

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Autores principales: Zarghi, Afshin, Javid, Farin Sattary, Ghodsi, Razieh, Dadrass, Orkideh G., Daraei, Bahram, Hedayati, Mehdi
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
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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.
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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
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