5-benzylidene-hydantoins as new EGFR inhibitors with antiproliferative activity.
A series of 1,5-disubstituted hydantoins, whose structure was designed to interact at the ATP-binding site of EGFR, was synthesized and evaluated for inhibition of EGFR kinase activity and antiproliferative action. Some of these compounds, characterized by a 1-phenethyl and a 5-(E)-benzylidene substituent, inhibited EGFR autophosphorylation and polyGAT phosphorylation, and also inhibited the growth and proliferation of human A431 cells, which overexpress EGFR. These compounds can therefore be regarded as examples of a new scaffold for tyrosine kinase inhibitors.
Carmi
Caterina
C
Dipartimento Farmaceutico, Università degli Studi di Parma, V.le G. P. Usberti 27/A, I-43100 Parma, Italy.
Cavazzoni
Andrea
A
Zuliani
Valentina
V
Lodola
Alessio
A
Bordi
Fabrizio
F
Plazzi
Pier Vincenzo
PV
Alfieri
Roberta R
RR
Petronini
Pier Giorgio
PG
Mor
Marco
M
D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D006801:Humans; D006827:Hydantoins / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D013329:Structure-Activity Relationship
D006827:Hydantoins; D066246:ErbB Receptors