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Design and development of ICCA as a dual inhibitor of GPIIb/IIIa and P-selectin receptors
BACKGROUND: The impact of upregulation of platelet membrane glycoprotein (GP)IIb/IIIa and P-selectin on the onset of arterial thrombosis, venous thrombosis, and cancer encourages to hypothesize that dual inhibitor of GPIIb/IIIa and P-selectin receptors should simultaneously inhibit arterial thrombos...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove Medical Press
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6042529/ https://www.ncbi.nlm.nih.gov/pubmed/30022809 http://dx.doi.org/10.2147/DDDT.S169238 |
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author | Chen, Haiyan Lu, An Zhang, Xiaoyi Gui, Lin Wang, Yaonan Wu, Jianhui Feng, Hua Peng, Shiqi Zhao, Ming |
author_facet | Chen, Haiyan Lu, An Zhang, Xiaoyi Gui, Lin Wang, Yaonan Wu, Jianhui Feng, Hua Peng, Shiqi Zhao, Ming |
author_sort | Chen, Haiyan |
collection | PubMed |
description | BACKGROUND: The impact of upregulation of platelet membrane glycoprotein (GP)IIb/IIIa and P-selectin on the onset of arterial thrombosis, venous thrombosis, and cancer encourages to hypothesize that dual inhibitor of GPIIb/IIIa and P-selectin receptors should simultaneously inhibit arterial thrombosis, block venous thrombosis, and slow tumor growth. METHODS: For this reason, the structural characteristics and the CDOCKER interaction energies of 12 carbolines were analyzed. This led to the design of 1-(4-isopropyl-phenyl)-β-carboline-3-carboxylic acid (ICCA) as a promising inhibitor of GPIIb/IIIa and P-selectin receptors. RESULTS: The synthetic route provided ICCA in 48% total yield and 99.6% high-performance liquid chromatography purity. In vivo 5 μmol/kg oral ICCA downregulated GPIIb/IIIa and P-selectin expression thereby inhibited arterial thrombosis, blocked venous thrombosis, and slowed down tumor growth, but did not damage the kidney and the liver. CONCLUSION: Therefore, ICCA could be a promising candidate capable of downregulating GPIIb/IIIa and P-selectin receptors, inhibiting arterial thrombosis, blocking venous thrombosis, and slowing down tumor growth. |
format | Online Article Text |
id | pubmed-6042529 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-60425292018-07-18 Design and development of ICCA as a dual inhibitor of GPIIb/IIIa and P-selectin receptors Chen, Haiyan Lu, An Zhang, Xiaoyi Gui, Lin Wang, Yaonan Wu, Jianhui Feng, Hua Peng, Shiqi Zhao, Ming Drug Des Devel Ther Original Research BACKGROUND: The impact of upregulation of platelet membrane glycoprotein (GP)IIb/IIIa and P-selectin on the onset of arterial thrombosis, venous thrombosis, and cancer encourages to hypothesize that dual inhibitor of GPIIb/IIIa and P-selectin receptors should simultaneously inhibit arterial thrombosis, block venous thrombosis, and slow tumor growth. METHODS: For this reason, the structural characteristics and the CDOCKER interaction energies of 12 carbolines were analyzed. This led to the design of 1-(4-isopropyl-phenyl)-β-carboline-3-carboxylic acid (ICCA) as a promising inhibitor of GPIIb/IIIa and P-selectin receptors. RESULTS: The synthetic route provided ICCA in 48% total yield and 99.6% high-performance liquid chromatography purity. In vivo 5 μmol/kg oral ICCA downregulated GPIIb/IIIa and P-selectin expression thereby inhibited arterial thrombosis, blocked venous thrombosis, and slowed down tumor growth, but did not damage the kidney and the liver. CONCLUSION: Therefore, ICCA could be a promising candidate capable of downregulating GPIIb/IIIa and P-selectin receptors, inhibiting arterial thrombosis, blocking venous thrombosis, and slowing down tumor growth. Dove Medical Press 2018-07-09 /pmc/articles/PMC6042529/ /pubmed/30022809 http://dx.doi.org/10.2147/DDDT.S169238 Text en © 2018 Chen et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. |
spellingShingle | Original Research Chen, Haiyan Lu, An Zhang, Xiaoyi Gui, Lin Wang, Yaonan Wu, Jianhui Feng, Hua Peng, Shiqi Zhao, Ming Design and development of ICCA as a dual inhibitor of GPIIb/IIIa and P-selectin receptors |
title | Design and development of ICCA as a dual inhibitor of GPIIb/IIIa and P-selectin receptors |
title_full | Design and development of ICCA as a dual inhibitor of GPIIb/IIIa and P-selectin receptors |
title_fullStr | Design and development of ICCA as a dual inhibitor of GPIIb/IIIa and P-selectin receptors |
title_full_unstemmed | Design and development of ICCA as a dual inhibitor of GPIIb/IIIa and P-selectin receptors |
title_short | Design and development of ICCA as a dual inhibitor of GPIIb/IIIa and P-selectin receptors |
title_sort | design and development of icca as a dual inhibitor of gpiib/iiia and p-selectin receptors |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6042529/ https://www.ncbi.nlm.nih.gov/pubmed/30022809 http://dx.doi.org/10.2147/DDDT.S169238 |
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