Department of Pharmaceutical Engineering, College of Chemistry and Chemical Engineering, Fuzhou University, Fujian 350108, PR China.
Eur J Med Chem. 2012 Oct;56:308-19. doi: 10.1016/j.ejmech.2012.07.047. Epub 2012 Aug 7.
A series of new emodin derivatives modified at the C-3 and the C-6 positions were synthesized, and evaluated for their anticancer activities in vitro and in vivo. Among them, Compounds 5g and 5h had more significant antiproliferative ability against HepG2, BGC-823, AGS cancer cell lines and low cytotoxicity to HELF normal cell line, respectively. Compounds 5g and 5h induced AGS cell cycle arrest at G0/G1 phase and induce apoptosis via activation of caspase-3 and caspase-9 enzyme. In vivo studies using H22 xenografts in Kunming mice were conducted with 5g and 5h. The results revealed that the medium dosage group (10 mg/kg) of 5g and the high dosage group (25 mg/kg) of 5h showed significant antitumor activity compared to the control group.
一系列在 C-3 和 C-6 位修饰的大黄素衍生物被合成，并在体外和体内评估其抗癌活性。其中，化合物 5g 和 5h 对 HepG2、BGC-823、AGS 癌细胞系的增殖抑制作用更为显著，对 HELF 正常细胞系的细胞毒性较低。化合物 5g 和 5h 通过激活 caspase-3 和 caspase-9 酶诱导 AGS 细胞周期停滞在 G0/G1 期，并诱导细胞凋亡。在昆明小鼠的 H22 异种移植中进行了 5g 和 5h 的体内研究。结果表明，与对照组相比，中剂量组（10mg/kg）的 5g 和高剂量组（25mg/kg）的 5h 表现出显著的抗肿瘤活性。
