Premium
Biological Evaluation and Structural Determinants of p38α Mitogen‐Activated‐Protein Kinase and c‐Jun‐N‐Terminal Kinase 3 Inhibition by Flavonoids
Author(s) -
Goettert Márcia,
Schattel Verena,
Koch Pierre,
Merfort Irmgard,
Laufer Stefan
Publication year - 2010
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201000487
Subject(s) - kinase , p38 mitogen activated protein kinases , chemistry , biochemistry , kaempferol , protein kinase a , mitogen activated protein kinase , luteolin , flavones , stereochemistry , flavonoid , chromatography , antioxidant
A series of 42 naturally occurring flavonoids and one flavonoid glucuronide were tested for their ability to inhibit p38α mitogen‐activated protein kinase (p38α) and c‐Jun‐N‐terminal kinase 3 (JNK3). Potent inhibitors with IC 50 values in the low micromolar range were identified. Structure–activity relationships were evaluated and the most promising compounds were docked into the ATP binding site of these kinases. Among the different classes of flavonoids, the flavonol group showed better inhibition of p38α. Of this class, kaempferol‐7,4′‐dimethylether was a potent p38α inhibitor, displaying 13‐fold selectivity for p38α over JNK3. The flavone compounds without a 6‐methoxy group preferentially inhibited JNK3. The flavone glycoside, luteolin‐7‐ O ‐glycoside, was identified as a potent inhibitor with the greatest selectivity toward JNK3. In contrast, the flavanol compounds displayed similar inhibitory activities toward both kinases.