1187307-84-1Relevant articles and documents
5-Benzylidene-hydantoins: Synthesis and antiproliferative activity on A549 lung cancer cell line
Zuliani, Valentina,Carmi, Caterina,Rivara, Mirko,Fantini, Marco,Lodola, Alessio,Vacondio, Federica,Bordi, Fabrizio,Plazzi, Pier Vincenzo,Cavazzoni, Andrea,Galetti, Maricla,Alfieri, Roberta R.,Petronini, Pier Giorgio,Mor, Marco
, p. 3471 - 3479 (2009)
Benzylidene hydantoins have been recently reported as a new class of EGFR inhibitors. We describe here a simple and efficient methodology for the parallel solution-phase synthesis of a library of 5-benzylidene hydantoins, which were evaluated for antiproliferative activity on the human lung adenocarcinoma A549 cell line. Various substituents at positions 1, 3 and 5 on the hydantoin nucleus were examined. In the presence of a 5-benzylidene group and of a lipophilic substituent at position 1, most of the tested compounds inhibited cell proliferation at a concentration of 20 μM. Compound 7 (UPR1024), bearing 1-phenethyl and (E)-5-p-OH-benzylidene substituents, was found to be the most active derivative of the series. It inhibited EGFR autophosphorylation and induced DNA damage in A549 cells. Compound 7 and other synthesized 5-benzylidene hydantoin derivatives increased p53 levels, suggesting that the dual mechanism of action was a common feature shared by compound 7 and other member of the series.
