Rizzi Eleonora, Cassinelli Giuliana, Dallavalle Sabrina, Lanzi Cinzia, Cincinelli Raffaella, Nannei Raffaella, Cuccuru Giuditta, Zunino Franco
Dipartimento di Scienze Molecolari Agroalimentari, Università di Milano, Via Celoria 2, 20133 Milano, Italy.
Bioorg Med Chem Lett. 2007 Jul 15;17(14):3962-8. doi: 10.1016/j.bmcl.2007.04.091. Epub 2007 Apr 30.
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.
