Wang Jiang, Su Mingbo, Li Tingting, Gao Anhui, Yang Wei, Sheng Li, Zang Yi, Li Jia, Liu Hong
CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, People's Republic of China.
CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, People's Republic of China.
Eur J Med Chem. 2017 Mar 10;128:293-299. doi: 10.1016/j.ejmech.2017.01.035. Epub 2017 Jan 23.
New thienopyrimidine hydroxamic acid derivatives as HDACs inhibitors were designed, synthesized and evaluated. All compounds were evaluated for their ability to inhibit recombinant human HDAC1, HDAC3, and HDAC6 isoforms and in vitro anti-proliferative activity on tumor cell lines RMPI 8226 and HCT 116. Most of these compounds displayed good to excellent inhibitory activities against HDACs. The IC values of compound 9m against HDAC1, HDAC3, and HDAC6 was 29.81 ± 0.52 nM, 24.71 ± 1.16 nM, and 21.29 ± 0.32 nM. Most of these compounds showed strong anti-proliferative activity against human cancer cell lines including RMPI 8226 and HCT 116. The IC values of compound 9m against RPMI 8226 and HCT 116 proliferation were 0.97 ± 0.072 μM and 1.01 ± 0.033 μM, respectively. In addition, compound 9m noticeably up-regulated the level of histone H3 acetylation at the low concentration of 0.3 μM.
设计、合成并评估了新型噻吩并嘧啶异羟肟酸衍生物作为组蛋白去乙酰化酶（HDACs）抑制剂。评估了所有化合物抑制重组人HDAC1、HDAC3和HDAC6亚型的能力以及对肿瘤细胞系RMPI 8226和HCT 116的体外抗增殖活性。这些化合物中的大多数对HDACs表现出良好至优异的抑制活性。化合物9m对HDAC1、HDAC3和HDAC6的IC值分别为29.81±0.52 nM、24.71±1.16 nM和21.29±0.32 nM。这些化合物中的大多数对包括RMPI 8226和HCT 116在内的人癌细胞系表现出较强的抗增殖活性。化合物9m对RPMI 8226和HCT 116增殖的IC值分别为0.97±0.072 μM和1.01±0.033 μM。此外，化合物9m在0.3 μM的低浓度下显著上调了组蛋白H3乙酰化水平。
