- 5-Benzylidene-hydantoins: Synthesis and antiproliferative activity on A549 lung cancer cell line
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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.
- 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
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experimental part
p. 3471 - 3479
(2009/12/24)
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- Amino acid and peptide synthesis and functionalization by the reaction of thioacids with 2,4-dinitrobenzenesulfonamides
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(Formula Presented) Readily prepared amino thioacids react at room temperature in DMF in the presence of cesium carbonate with 2,4- dinitrobenzenesulfonamides to give amides. When the sulfonamide is derived from an amino acid the method results in peptide bond formation, whereas the use of carbohydrate derived sulfonamides gives neoglycoconjugates.
- Crich, David,Sana, Kasinath,Guo, Songpo
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p. 4423 - 4426
(2008/03/12)
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- 5-Benzylidene-hydantoins as new EGFR inhibitors with antiproliferative activity
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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 b
- Carmi, Caterina,Cavazzoni, Andrea,Zuliani, Valentina,Lodola, Alessio,Bordi, Fabrizio,Plazzi, Pier Vincenzo,Alfieri, Roberta R.,Petronini, Pier Giorgio,Mor, Marco
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p. 4021 - 4025
(2007/10/03)
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