title: Synthesis and RET protein kinase inhibitory activity of 3-arylureidobenzylidene-indolin-2-ones.
abstract: A novel series of 3-arylureidobenzylidene-indolin-2-ones was synthesized and their inhibitory activity against Ret tyrosine kinase investigated in comparison with the Ret inhibitor RPI-1 as a reference compound for this series. A few compounds were able to revert the RETC634R oncogene-transformed morphologic phenotype of NIH3T3(MEN2A) cells and showed a selective antiproliferative activity against these cells as compared to parental NIH3T3 cells or NIH3T3 cells transformed with a non-tyrosine kinase oncogene (NIH3T3(H-RAS)). Inhibition of Ret enzyme activity by effective derivatives was confirmed in a kinase assay. Structure-activity relationship indicated a favourable activity for 5,6-dimethoxyindolinone derivatives with H, OH, or OMe in the para position of the distal aryl ring.
authors.affiliation: Dipartimento di Scienze Molecolari Agroalimentari, Università di Milano, Via Celoria 2, 20133 Milano, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Rizzi
authors.forename: Giuliana
authors.initials: G
authors.lastname: Cassinelli
authors.forename: Sabrina
authors.initials: S
authors.lastname: Dallavalle
authors.forename: Cinzia
authors.initials: C
authors.lastname: Lanzi
authors.forename: Raffaella
authors.initials: R
authors.lastname: Cincinelli
authors.forename: Raffaella
authors.initials: R
authors.lastname: Nannei
authors.forename: Giuditta
authors.initials: G
authors.lastname: Cuccuru
authors.forename: Franco
authors.initials: F
authors.lastname: Zunino
mesh_terms: D000818:Animals; D015153:Blotting, Western; D007211:Indoles / Q000138:chemical synthesis / Q000494:pharmacology*; D051379:Mice; D041681:NIH 3T3 Cells; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D051096:Proto-Oncogene Proteins c-ret / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D007211:Indoles; D047428:Protein Kinase Inhibitors; D051096:Proto-Oncogene Proteins c-ret; C494999:Ret protein, mouse