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Sulfenamide and Sulfonamide Derivatives of Metformin – A New Option to Improve Endothelial Function and Plasma Haemostasis

Type 2 diabetes mellitus (T2DM) is a multi-factorial disease which can cause multiple organ dysfunction, including that of the vascular endothelium. The aim of the present study was to evaluate the effects of metformin, and its sulfenamide and sulfonamide derivatives (compounds 1–8) on the selected...

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Autores principales: Markowicz-Piasecka, Magdalena, Huttunen, Kristiina M., Broncel, Marlena, Sikora, Joanna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6484023/
https://www.ncbi.nlm.nih.gov/pubmed/31024058
http://dx.doi.org/10.1038/s41598-019-43083-z
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author Markowicz-Piasecka, Magdalena
Huttunen, Kristiina M.
Broncel, Marlena
Sikora, Joanna
author_facet Markowicz-Piasecka, Magdalena
Huttunen, Kristiina M.
Broncel, Marlena
Sikora, Joanna
author_sort Markowicz-Piasecka, Magdalena
collection PubMed
description Type 2 diabetes mellitus (T2DM) is a multi-factorial disease which can cause multiple organ dysfunction, including that of the vascular endothelium. The aim of the present study was to evaluate the effects of metformin, and its sulfenamide and sulfonamide derivatives (compounds 1–8) on the selected markers of endothelial function and blood coagulation. The integrity of endothelial cells(ECs) was examined using the real-time cell electric impedance system. Tissue Factor(TF) production, the release of von Willebrand Factor (vWF) and tissue plasminogen activator(t-PA) from ECs were determined using immunoenzymatic assays, while the process of platelet thrombus formation using the Total Thrombus-Formation Analysis System. Sulfenamide with n-butyl alkyl chain(3) does not interfere with ECs integrity, and viability (nCI((24h)) = 1.03 ± 0.03 vs. 1.06 ± 0.11 for control), but possesses anticoagulation properties manifested by prolonged platelet-dependent thrombus formation (Occlusion Time 370.3 ± 77.0 s vs. 286.7 ± 65.5 s for control) in semi-physiological conditions. Both p- and o-nitro-benzenesulfonamides (compounds7,8) exhibit anti-coagulant properties demonstrated by decreased vWF release and prolonged parameters of platelet thrombus formation and total blood thrombogenicity. In conclusion, chemical modification of metformin scaffold into sulfenamides or sulfonamides might be regarded as a good starting point for the design and synthesis of novel biguanide-based compounds with anticoagulant properties and valuable features regarding endothelial function.
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spelling pubmed-64840232019-05-13 Sulfenamide and Sulfonamide Derivatives of Metformin – A New Option to Improve Endothelial Function and Plasma Haemostasis Markowicz-Piasecka, Magdalena Huttunen, Kristiina M. Broncel, Marlena Sikora, Joanna Sci Rep Article Type 2 diabetes mellitus (T2DM) is a multi-factorial disease which can cause multiple organ dysfunction, including that of the vascular endothelium. The aim of the present study was to evaluate the effects of metformin, and its sulfenamide and sulfonamide derivatives (compounds 1–8) on the selected markers of endothelial function and blood coagulation. The integrity of endothelial cells(ECs) was examined using the real-time cell electric impedance system. Tissue Factor(TF) production, the release of von Willebrand Factor (vWF) and tissue plasminogen activator(t-PA) from ECs were determined using immunoenzymatic assays, while the process of platelet thrombus formation using the Total Thrombus-Formation Analysis System. Sulfenamide with n-butyl alkyl chain(3) does not interfere with ECs integrity, and viability (nCI((24h)) = 1.03 ± 0.03 vs. 1.06 ± 0.11 for control), but possesses anticoagulation properties manifested by prolonged platelet-dependent thrombus formation (Occlusion Time 370.3 ± 77.0 s vs. 286.7 ± 65.5 s for control) in semi-physiological conditions. Both p- and o-nitro-benzenesulfonamides (compounds7,8) exhibit anti-coagulant properties demonstrated by decreased vWF release and prolonged parameters of platelet thrombus formation and total blood thrombogenicity. In conclusion, chemical modification of metformin scaffold into sulfenamides or sulfonamides might be regarded as a good starting point for the design and synthesis of novel biguanide-based compounds with anticoagulant properties and valuable features regarding endothelial function. Nature Publishing Group UK 2019-04-25 /pmc/articles/PMC6484023/ /pubmed/31024058 http://dx.doi.org/10.1038/s41598-019-43083-z Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Markowicz-Piasecka, Magdalena
Huttunen, Kristiina M.
Broncel, Marlena
Sikora, Joanna
Sulfenamide and Sulfonamide Derivatives of Metformin – A New Option to Improve Endothelial Function and Plasma Haemostasis
title Sulfenamide and Sulfonamide Derivatives of Metformin – A New Option to Improve Endothelial Function and Plasma Haemostasis
title_full Sulfenamide and Sulfonamide Derivatives of Metformin – A New Option to Improve Endothelial Function and Plasma Haemostasis
title_fullStr Sulfenamide and Sulfonamide Derivatives of Metformin – A New Option to Improve Endothelial Function and Plasma Haemostasis
title_full_unstemmed Sulfenamide and Sulfonamide Derivatives of Metformin – A New Option to Improve Endothelial Function and Plasma Haemostasis
title_short Sulfenamide and Sulfonamide Derivatives of Metformin – A New Option to Improve Endothelial Function and Plasma Haemostasis
title_sort sulfenamide and sulfonamide derivatives of metformin – a new option to improve endothelial function and plasma haemostasis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6484023/
https://www.ncbi.nlm.nih.gov/pubmed/31024058
http://dx.doi.org/10.1038/s41598-019-43083-z
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