Synthesis and RET protein kinase inhibitory activity of 3-arylureidobenzylidene-indolin-2-ones.
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.
Rizzi
Eleonora
E
Dipartimento di Scienze Molecolari Agroalimentari, Università di Milano, Via Celoria 2, 20133 Milano, Italy.
Cassinelli
Giuliana
G
Dallavalle
Sabrina
S
Lanzi
Cinzia
C
Cincinelli
Raffaella
R
Nannei
Raffaella
R
Cuccuru
Giuditta
G
Zunino
Franco
F
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
D007211:Indoles; D047428:Protein Kinase Inhibitors; D051096:Proto-Oncogene Proteins c-ret; C494999:Ret protein, mouse