Synthesis and Biological Evaluation of 1-(2-Aminophenyl)-3-arylurea Derivatives as Potential EphA2 and HDAC Dual Inhibitors

抄録

A series of 1-(2-aminophenyl)-3-arylurea novel derivatives were synthesized and evaluated against Ephrin type-A receptor 2 (EphA2) and histone deacetylases (HDACs) kinase. Most of the compounds exhibited inhibitory activity against EphA2 and HDAC. The antiproliferative activities were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) (thiazolyl blue, tetrazolium blue) against the human cancer cell lines HCT116, K562 and MCF7. Compounds 5a and b showed the most potent inhibitory activity against EphA2 and HDAC. However, compound 5b exhibited higher potency against HCT116 (IC₅₀=5.29 µM) and MCF7 (IC₅₀=7.42 µM). 1-(2-Aminophenyl)-3-arylurea analogues may serve as new EphA2–HDAC dual inhibitors.