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 microM. 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.

5-Benzylidene-hydantoins: synthesis and antiproliferative activity on A549 lung cancer cell line / Zuliani, Valentina; Carmi, Caterina; Rivara, Mirko; Fantini, M; Lodola, Alessio; Vacondio, Federica; Bordi, Fabrizio; Plazzi, Pier Vincenzo; Cavazzoni, Andrea; Galetti, Maricla; Alfieri, Roberta; Petronini, Pier Giorgio; Mor, Marco. - In: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0223-5234. - 44:(2009), pp. 3471-3479. [10.1016/j.ejmech.2009.01.035]

5-Benzylidene-hydantoins: synthesis and antiproliferative activity on A549 lung cancer cell line

ZULIANI, Valentina;CARMI, Caterina;RIVARA, Mirko;LODOLA, Alessio;VACONDIO, Federica;BORDI, Fabrizio;PLAZZI, Pier Vincenzo;CAVAZZONI, Andrea;GALETTI, Maricla;ALFIERI, Roberta;PETRONINI, Pier Giorgio;MOR, Marco
2009-01-01

Abstract

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 microM. 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.
5-Benzylidene-hydantoins: synthesis and antiproliferative activity on A549 lung cancer cell line / Zuliani, Valentina; Carmi, Caterina; Rivara, Mirko; Fantini, M; Lodola, Alessio; Vacondio, Federica; Bordi, Fabrizio; Plazzi, Pier Vincenzo; Cavazzoni, Andrea; Galetti, Maricla; Alfieri, Roberta; Petronini, Pier Giorgio; Mor, Marco. - In: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0223-5234. - 44:(2009), pp. 3471-3479. [10.1016/j.ejmech.2009.01.035]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2293746
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