Gu Wen, Miao Ting-Ting, Hua Da-Wei, Jin Xiao-Yan, Tao Xu-Bing, Huang Chao-Bo, Wang Shi-Fa
Jiangsu Key Lab of Biomass-based Green Fuels and Chemicals, College of Chemical Engineering, Nanjing Forestry University, Nanjing 210037, PR China.
Jiangsu Key Lab of Biomass-based Green Fuels and Chemicals, College of Chemical Engineering, Nanjing Forestry University, Nanjing 210037, PR China.
Bioorg Med Chem Lett. 2017 Mar 1;27(5):1296-1300. doi: 10.1016/j.bmcl.2017.01.028. Epub 2017 Jan 13.
A series of new 1H-benzo[d]imidazole derivatives of dehydroabietic acid were designed and synthesized as potent antitumor agents. Structures of the target molecules were characterized using MS, IR, H NMR, C NMR and elemental analyses. In the in vitro cytotoxic assay, most compounds showed significant cytotoxic activities against two hepatocarcinoma cells (SMMC-7721 and HepG2) and reduced cytotoxicity against noncancerous human hepatocyte (LO2). Among them, compound 7b exhibited the best cytotoxicity against SMMC-7721 cells (IC: 0.36±0.13μM), while 7e was most potent to HepG2 cells (IC: 0.12±0.03μM). The cell cycle analysis indicated that compound 7b caused cell cycle arrest of SMMC-7721 cells at G2/M phase. Further, compound 7b also induced the apoptosis of SMMC-7721 cells in Annexin V-APC/7-AAD binding assay.
设计并合成了一系列新的脱氢枞酸1H-苯并[d]咪唑衍生物作为强效抗肿瘤剂。通过质谱、红外光谱、氢核磁共振、碳核磁共振和元素分析对目标分子的结构进行了表征。在体外细胞毒性试验中，大多数化合物对两种肝癌细胞（SMMC-7721和HepG2）表现出显著的细胞毒性活性，而对非癌性人肝细胞（LO2）的细胞毒性降低。其中，化合物7b对SMMC-7721细胞表现出最佳的细胞毒性（IC：0.36±0.13μM），而7e对HepG2细胞最有效（IC：0.12±0.03μM）。细胞周期分析表明，化合物7b使SMMC-7721细胞在G2/M期发生细胞周期阻滞。此外，在膜联蛋白V-APC/7-AAD结合试验中，化合物7b还诱导了SMMC-7721细胞的凋亡。
