Two new fluorophenylindenone derivatives were designed as potential p38α MAPK modulators by preserving the key interactions of the vicinal pyridine/fluorophenyl pharmacophore with the enzyme protein. Interestingly, these two fluorophenylindenone isomers showed divergent activities, with compound 6 behaving as an inhibitor and 5 as a putative activator. These results were rationalized by docking studies and molecular dynamics simulations in terms of stabilization of DFG loop, by compound 5 in a conformation more accessible to phosphorylation.
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|Titolo:||Phenylindenone isomers as divergent modulators of p38α MAP kinase|
|Citazione:||CAPPELLI, A., NANNICINI, C., CHELINI, A., PAOLINO, M., GIULIANI, G., ANZINI, M., et al. (2016). Phenylindenone isomers as divergent modulators of p38α MAP kinase. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 26(21), 5160-5163.|
|Appare nelle tipologie:||1.1 Articolo in rivista|