Synthesis, Inhibitory Activity, and In Silico Modeling of Selective COX-1 Inhibitors with a Quinazoline Core

[Image: see text] Selective cyclooxygenase-1 (COX-1) inhibition has got into the spotlight with the discovery of COX-1 upregulation in various cancers and the cardioprotective role of COX-1 in control of thrombocyte aggregation. Yet, COX-1-selective inhibitors are poorly explored. Thus, three series...

Descripción completa

Detalles Bibliográficos
Autores principales: Dvorakova, Marcela, Langhansova, Lenka, Temml, Veronika, Pavicic, Antonio, Vanek, Tomas, Landa, Premysl
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2021
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040043/
https://www.ncbi.nlm.nih.gov/pubmed/33854702
http://dx.doi.org/10.1021/acsmedchemlett.1c00004
_version_ 1783677710351990784
author Dvorakova, Marcela
Langhansova, Lenka
Temml, Veronika
Pavicic, Antonio
Vanek, Tomas
Landa, Premysl
author_facet Dvorakova, Marcela
Langhansova, Lenka
Temml, Veronika
Pavicic, Antonio
Vanek, Tomas
Landa, Premysl
author_sort Dvorakova, Marcela
collection PubMed
description [Image: see text] Selective cyclooxygenase-1 (COX-1) inhibition has got into the spotlight with the discovery of COX-1 upregulation in various cancers and the cardioprotective role of COX-1 in control of thrombocyte aggregation. Yet, COX-1-selective inhibitors are poorly explored. Thus, three series of quinazoline derivatives were prepared and tested for their potential inhibitory activity toward COX-1 and COX-2. Of the prepared compounds, 11 exhibited interesting COX-1 selectivity, with 8 compounds being totally COX-1-selective. The IC(50) value of the best quinazoline inhibitor was 64 nM. The structural features ensuring COX-1 selectivity were elucidated using in silico modeling.
format Online
Article
Text
id pubmed-8040043
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher American Chemical Society
record_format MEDLINE/PubMed
spelling pubmed-80400432021-04-13 Synthesis, Inhibitory Activity, and In Silico Modeling of Selective COX-1 Inhibitors with a Quinazoline Core Dvorakova, Marcela Langhansova, Lenka Temml, Veronika Pavicic, Antonio Vanek, Tomas Landa, Premysl ACS Med Chem Lett [Image: see text] Selective cyclooxygenase-1 (COX-1) inhibition has got into the spotlight with the discovery of COX-1 upregulation in various cancers and the cardioprotective role of COX-1 in control of thrombocyte aggregation. Yet, COX-1-selective inhibitors are poorly explored. Thus, three series of quinazoline derivatives were prepared and tested for their potential inhibitory activity toward COX-1 and COX-2. Of the prepared compounds, 11 exhibited interesting COX-1 selectivity, with 8 compounds being totally COX-1-selective. The IC(50) value of the best quinazoline inhibitor was 64 nM. The structural features ensuring COX-1 selectivity were elucidated using in silico modeling. American Chemical Society 2021-03-12 /pmc/articles/PMC8040043/ /pubmed/33854702 http://dx.doi.org/10.1021/acsmedchemlett.1c00004 Text en © 2021 American Chemical Society Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Dvorakova, Marcela
Langhansova, Lenka
Temml, Veronika
Pavicic, Antonio
Vanek, Tomas
Landa, Premysl
Synthesis, Inhibitory Activity, and In Silico Modeling of Selective COX-1 Inhibitors with a Quinazoline Core
title Synthesis, Inhibitory Activity, and In Silico Modeling of Selective COX-1 Inhibitors with a Quinazoline Core
title_full Synthesis, Inhibitory Activity, and In Silico Modeling of Selective COX-1 Inhibitors with a Quinazoline Core
title_fullStr Synthesis, Inhibitory Activity, and In Silico Modeling of Selective COX-1 Inhibitors with a Quinazoline Core
title_full_unstemmed Synthesis, Inhibitory Activity, and In Silico Modeling of Selective COX-1 Inhibitors with a Quinazoline Core
title_short Synthesis, Inhibitory Activity, and In Silico Modeling of Selective COX-1 Inhibitors with a Quinazoline Core
title_sort synthesis, inhibitory activity, and in silico modeling of selective cox-1 inhibitors with a quinazoline core
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040043/
https://www.ncbi.nlm.nih.gov/pubmed/33854702
http://dx.doi.org/10.1021/acsmedchemlett.1c00004
work_keys_str_mv AT dvorakovamarcela synthesisinhibitoryactivityandinsilicomodelingofselectivecox1inhibitorswithaquinazolinecore
AT langhansovalenka synthesisinhibitoryactivityandinsilicomodelingofselectivecox1inhibitorswithaquinazolinecore
AT temmlveronika synthesisinhibitoryactivityandinsilicomodelingofselectivecox1inhibitorswithaquinazolinecore
AT pavicicantonio synthesisinhibitoryactivityandinsilicomodelingofselectivecox1inhibitorswithaquinazolinecore
AT vanektomas synthesisinhibitoryactivityandinsilicomodelingofselectivecox1inhibitorswithaquinazolinecore
AT landapremysl synthesisinhibitoryactivityandinsilicomodelingofselectivecox1inhibitorswithaquinazolinecore

Ejemplares similares