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Biological Evaluation and Structural Determinants of p38α Mitogen-Activated-Protein Kinase and c-Jun-N-Terminal Kinase 3 Inhibition by Flavonoids

✍ Scribed by Márcia Goettert; Verena Schattel; Dr. Pierre Koch; Prof. Dr. Irmgard Merfort; Prof. Dr. Stefan Laufer

Publisher
John Wiley and Sons
Year
2010
Tongue
English
Weight
746 KB
Volume
11
Category
Article
ISSN
1439-4227

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✦ Synopsis

Abstract

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.

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