Synthesis of diphenylamine macrocycles and their anti-inflammatory effects

A collection of fourteen diphenylamine macrocyclic derivatives containing a peptide chain with different substituents was synthesized using a protocol of two Ugi four component reactions (Ugi-4CR) and a Buchwald-Hartwig macrocyclization. Their anti-inflammatory effects were assayed with an ear edema...

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Bibliographic Details
Published in:Organic & biomolecular chemistry 2019-02, Vol.17 (6), p.1423-1435
Main Authors: Chávez-Riveros, Alejandra, Hernández-Vázquez, Eduardo, Nieto-Camacho, Antonio, Ramírez-Apan, Teresa, Miranda, Luis D
Format: Article
Language:English
Subjects:
12-O-Tetradecanoylphorbol-13-acetate
Acetic acid
Biological activity
Celecoxib
Cell lines
Chemical synthesis
Crystallography
Cytotoxicity
Ear
Edema
Indomethacin
Infiltration
Inflammation
Leukocytes
NMR
Nuclear magnetic resonance
Peroxidase
Toxicity
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Summary:A collection of fourteen diphenylamine macrocyclic derivatives containing a peptide chain with different substituents was synthesized using a protocol of two Ugi four component reactions (Ugi-4CR) and a Buchwald-Hartwig macrocyclization. Their anti-inflammatory effects were assayed with an ear edema model using 12- O -tetradecanoylphorbol-13-acetate, while the activity of myeloperoxidase was determined to evaluate the index of leukocyte infiltration. Compound 5e had an ID 50 of 0.18 μM per ear with a potency higher than that of the reference drugs indomethacin and celecoxib (0.24 and 0.91 μM per ear, respectively). Moreover, the cytotoxicity of the macrocycles was determined in two healthy cell lines, showing a low percentage of toxicity. A collection of fourteen diphenylamine macrocyclic derivatives containing a peptide chain with different substituents was synthesized using a protocol of two Ugi four component reactions (Ugi-4CR) and a Buchwald-Hartwig macrocyclization.
ISSN:1477-0520
1477-0539
DOI:10.1039/c8ob03121e