- 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 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.
- Maczynski, Marcin,Borska, Sylwia,Miesza?a, Katarzyna,Kocieba, Maja,Zaczynska, Ewa,Kochanowska, Iwona,Zimecki, Micha?
-
-
Read Online
- Nucleophilic substitution of an acyl azide: General method for the preparation of 5-amino-3-methyl-4-isoxazolecarboxylic acid amides and hydrazides
-
We describe a convenient and general method for preparation of 5-amino-3-methyl-4-isoxazolecarboxylic acid amides and hydrazines from 5-amino-3-methyl-4-isoxazolecarboxylic acid azide. In this reaction, the acyl azide reacts with amines without Curtius re
- Ryng, Stanislaw,Glowiak, Tadeusz
-
p. 1359 - 1368
(2007/10/03)
-