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.

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 [10.1016/j.bmcl.2016.10.001].

Phenylindenone isomers as divergent modulators of p38α MAP kinase

CAPPELLI, ANDREA;NANNICINI, CHIARA;CHELINI, ALESSIA;PAOLINO, MARCO;GIULIANI, GERMANO;ANZINI, MAURIZIO;GIORGI, GIANLUCA;VOMERO, SALVATORE;
2016-01-01

Abstract

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.
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 [10.1016/j.bmcl.2016.10.001].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11365/998341
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