Cai Jin, Wei Hongtao, Hong Kwon Ho, Wu Xiaoqing, Zong Xi, Cao Meng, Wang Peng, Li Lushen, Sun Chunlong, Chen Bo, Zhou Gaoxing, Chen Junqing, Ji Min
School of Chemistry and Chemical Engineering, Institute of Pharmaceutical Engineering, Southeast University, 87 Dingjiaqiao, Nanjing, Jiangsu 210096, PR China.
College of Chemistry and Pharmaceutical Sciences, Qingdao Agricultural University, Qingdao 266109, PR China.
Bioorg Med Chem. 2015 Jul 1;23(13):3457-71. doi: 10.1016/j.bmc.2015.04.028. Epub 2015 Apr 16.
In our study, three series of hydroxamate, 2-aminobenzamide, and trifluoromethyl ketone analogues have been designed and synthesized. The synthesized compounds were investigated for their in vitro antiproliferative activities using the MTT-based assay against three human cancer cell lines including A549, NCI-H661, and U937. Most analogues exhibited higher antiproliferative activities against human acute myeloid leukemia cell U937 than the other two human lung cancer cell lines. Furthermore, the compounds were examined against HDAC1, 2, and 8 isoforms. Docking study of compounds 6h, 9b, and 10a suggested that they might bind tightly to the binding pocket of HDAC2 and/or HDAC8. The results suggest that these compounds might have potential as lead compounds for the development of anti-tumor drugs with HDACs inhibitory activities.
在我们的研究中，设计并合成了三类异羟肟酸、2-氨基苯甲酰胺和三氟甲基酮类似物。使用基于MTT的检测方法，针对包括A549、NCI-H661和U937在内的三种人类癌细胞系，对合成的化合物进行了体外抗增殖活性研究。大多数类似物对人急性髓性白血病细胞U937的抗增殖活性高于另外两种人肺癌细胞系。此外，还针对HDAC1、2和8亚型对这些化合物进行了检测。化合物6h、9b和10a的对接研究表明，它们可能与HDAC2和/或HDAC8的结合口袋紧密结合。结果表明，这些化合物可能具有作为开发具有HDAC抑制活性的抗肿瘤药物的先导化合物的潜力。
