5-Amino-3-methyl-4-isoxazolecarboxylic acid hydrazide derivatives with in vitro immunomodulatory activities
| Autor: | Angelika Drynda, Marcin Mączyński, Stanisław Ryng, Bożena Obmińska-Mrukowicz, Iwona Kochanowska, Michał Zimecki, Ewa Zaczyńska |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Lipopolysaccharides
0301 basic medicine medicine.medical_treatment Interleukin-1beta Lymphocyte proliferation Pharmacology Hydrazide Biochemistry Jurkat cells Jurkat Cells Mice 03 medical and health sciences chemistry.chemical_compound Peritoneal cavity 0302 clinical medicine Drug Discovery medicine Animals Humans Cells Cultured Cell Proliferation Mice Inbred BALB C biology Caspase 3 Tumor Necrosis Factor-alpha Organic Chemistry Isoxazoles Caspase 9 030104 developmental biology medicine.anatomical_structure Cytokine chemistry Mechanism of action Concanavalin A Cell culture 030220 oncology & carcinogenesis Macrophages Peritoneal biology.protein Molecular Medicine medicine.symptom Immunosuppressive Agents Leflunomide Signal Transduction |
| Zdroj: | Chemical Biology & Drug Design. 89:705-713 |
| ISSN: | 1747-0277 |
| DOI: | 10.1111/cbdd.12892 |
| Popis: | Isoxazoles are an important class of compounds of potential therapeutic value. The aim of this study was to determine immunotropic effects of 5-amino-3-methyl-4-isoxazolecarboxylic acid hydrazide derivatives on spontaneous and mitogen-induced lymphocyte proliferation in young and old mice, cytokine production by peritoneal cells as well as possible mechanism of action in a model of Jurkat cells. Three month and thirteen month old BALB/c mice were used as donors of the cells from a thymus, a spleen, mesenteric lymph nodes and a peritoneal cavity. Spontaneous and concanavalin A (ConA) or lipopolysaccharide (LPS)-induced cell proliferation was measured by MTT colorimetric method. IL-1β and TNF-α production induced by LPS in macrophage-enriched peritoneal cell cultures was measured by enzyme-linked immunoassay. 5-amino-3-methyl-4-isoxazolecarboxylic acid hydrazide, 01K (4-phenyl-1-(5-amino-3-methylisoxazole-4-carbonyl)-thiosemicarbazide) and 06K (4-(4-chlorophenyl)-1-(5-amino-3-methylisoxazole-4-carbonyl)-thiosemicarbazide) exhibited regulatory activity in the proliferation tests. Prevailing stimulatory activity of the hydrazide and inhibitory activity of 01K and 06K was observed. Those effects were connected with different influence of the compounds on signaling proteins expression in Jurkat cells. The regulatory effects of the compounds on IL-1β production were more profound than those on TNF-α. Differences in the compound activity in young vs. old mice were mainly restricted to 01K. Immunosuppressive isoxazole leflunomide and a stimulatory RM-11 (1,7-dimethyl-8-oxo-1,2H-isoxazole[5,4-e] triazepine) were applied as reference drugs. This article is protected by copyright. All rights reserved. |
| Databáze: | OpenAIRE |
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