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Synthesis, Immunosuppressive Properties, and Mechanism of Action of a New Isoxazole Derivative
This work describes the synthesis of a new series of isoxazole derivatives, their immunosuppressive properties, and the mechanism of action of a representative compound. A new series of N′-substituted derivatives of 5-amino-N,3-dimethyl-1,2-oxazole-4-carbohydrazide (MM1–MM10) was synthesized in reac...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6099534/ https://www.ncbi.nlm.nih.gov/pubmed/29949951 http://dx.doi.org/10.3390/molecules23071545 |
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author | Mączyński, Marcin Borska, Sylwia Mieszała, Katarzyna Kocięba, Maja Zaczyńska, Ewa Kochanowska, Iwona Zimecki, Michał |
author_facet | Mączyński, Marcin Borska, Sylwia Mieszała, Katarzyna Kocięba, Maja Zaczyńska, Ewa Kochanowska, Iwona Zimecki, Michał |
author_sort | Mączyński, Marcin |
collection | PubMed |
description | This work describes the synthesis of a new series of isoxazole derivatives, their immunosuppressive properties, and the mechanism of action of a representative compound. A new series of N′-substituted derivatives of 5-amino-N,3-dimethyl-1,2-oxazole-4-carbohydrazide (MM1–MM10) was synthesized in reaction of 5-amino-N,3-dimethyl-1,2-oxazole-4-carbohydrazide with relevant carbonyl compounds. The isoxazole derivatives were tested in several in vitro models using human cells. The compounds inhibited phytohemagglutinin A (PHA)-induced proliferation of peripheral blood mononuclear cells (PBMCs) to various degrees. The toxicity of the compounds with regard to a reference A549 cell line was also differential. 5-amino-N′-(2,4-dihydroxyphenyl)methylidene-N,3-dimethyl-1,2-oxazole-4-carbohydrazide (MM3) compound was selected for further investigation because of its lack of toxicity and because it had the strongest antiproliferative activity. The compound was shown to inhibit lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF α) production in human whole blood cell cultures. In the model of Jurkat cells, MM3 elicited strong increases in the expression of caspases, Fas, and NF-κB1, indicating that a proapoptotic action may account for its immunosuppressive action in the studied models. |
format | Online Article Text |
id | pubmed-6099534 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-60995342018-11-13 Synthesis, Immunosuppressive Properties, and Mechanism of Action of a New Isoxazole Derivative Mączyński, Marcin Borska, Sylwia Mieszała, Katarzyna Kocięba, Maja Zaczyńska, Ewa Kochanowska, Iwona Zimecki, Michał Molecules Article This work describes the synthesis of a new series of isoxazole derivatives, their immunosuppressive properties, and the mechanism of action of a representative compound. A new series of N′-substituted derivatives of 5-amino-N,3-dimethyl-1,2-oxazole-4-carbohydrazide (MM1–MM10) was synthesized in reaction of 5-amino-N,3-dimethyl-1,2-oxazole-4-carbohydrazide with relevant carbonyl compounds. The isoxazole derivatives were tested in several in vitro models using human cells. The compounds inhibited phytohemagglutinin A (PHA)-induced proliferation of peripheral blood mononuclear cells (PBMCs) to various degrees. The toxicity of the compounds with regard to a reference A549 cell line was also differential. 5-amino-N′-(2,4-dihydroxyphenyl)methylidene-N,3-dimethyl-1,2-oxazole-4-carbohydrazide (MM3) compound was selected for further investigation because of its lack of toxicity and because it had the strongest antiproliferative activity. The compound was shown to inhibit lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF α) production in human whole blood cell cultures. In the model of Jurkat cells, MM3 elicited strong increases in the expression of caspases, Fas, and NF-κB1, indicating that a proapoptotic action may account for its immunosuppressive action in the studied models. MDPI 2018-06-26 /pmc/articles/PMC6099534/ /pubmed/29949951 http://dx.doi.org/10.3390/molecules23071545 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Mączyński, Marcin Borska, Sylwia Mieszała, Katarzyna Kocięba, Maja Zaczyńska, Ewa Kochanowska, Iwona Zimecki, Michał Synthesis, Immunosuppressive Properties, and Mechanism of Action of a New Isoxazole Derivative |
title | Synthesis, Immunosuppressive Properties, and Mechanism of Action of a New Isoxazole Derivative |
title_full | Synthesis, Immunosuppressive Properties, and Mechanism of Action of a New Isoxazole Derivative |
title_fullStr | Synthesis, Immunosuppressive Properties, and Mechanism of Action of a New Isoxazole Derivative |
title_full_unstemmed | Synthesis, Immunosuppressive Properties, and Mechanism of Action of a New Isoxazole Derivative |
title_short | Synthesis, Immunosuppressive Properties, and Mechanism of Action of a New Isoxazole Derivative |
title_sort | synthesis, immunosuppressive properties, and mechanism of action of a new isoxazole derivative |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6099534/ https://www.ncbi.nlm.nih.gov/pubmed/29949951 http://dx.doi.org/10.3390/molecules23071545 |
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