Add time:07/11/2019         Source:sciencedirect.com

A series of 21 novel N1-(2-aryl-1,3-thiazolidin-4-one)-N3-aryl urea derivatives based on the previously identified lead compound I were synthesized and biologically characterized. The most promising compound 19a was identified as a multi-tyrosine kinase inhibitor, including c-Met, Ron, c-Kit, AXL and IGF-1R, etc. The results of real-time live-cell imaging indicated that compound 19a showed improved cytotoxicity and anti-proliferative activity against HT-29 cancer cells in a time- and dose-dependent manner, with an efficacy that was significantly greater than Cabozantinib. Flow cytometry and western blot analysis demonstrated the fact that anticancer activity was closely related with cancer cell apoptosis and the blockade of the phosphorylation of c-Met and its downstream signaling ERK and Akt. Furthermore, compound 19a also displayed slightly stronger effects on HT-29 cancer cells migration than that of Cabozantinib.

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