Zhu Yong, Ran Ting, Chen Xin, Niu Jiaqi, Zhao Shuang, Lu Tao, Tang Weifang
Department of Organic Chemistry, China Pharmaceutical University.
Chem Pharm Bull (Tokyo). 2016;64(8):1136-41. doi: 10.1248/cpb.c16-00154.
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.
合成了一系列新型的1-(2-氨基苯基)-3-芳基脲衍生物，并对其针对Ephrin A型受体2（EphA2）和组蛋白脱乙酰酶（HDACs）激酶进行了评估。大多数化合物对EphA2和HDAC表现出抑制活性。通过3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT，噻唑蓝，四氮唑蓝）针对人癌细胞系HCT116、K562和MCF7评估了其抗增殖活性。化合物5a和5b对EphA2和HDAC表现出最强的抑制活性。然而，化合物5b对HCT116（IC50 = 5.29 μM）和MCF7（IC50 = 7.42 μM）表现出更高的活性。1-(2-氨基苯基)-3-芳基脲类似物可能作为新型的EphA2-HDAC双重抑制剂。
